The CLL Ranch

Reports of My Death Have Only Been Slightly Exaggerated

2011-11-23T09:48:00.000-08:00

I've been back in the hospital with more problems. To make a long, terrible, miserable story short, I'm off the CAL-101 and on prednisone. The operating theory from Dr. Coutre is that I have colonitis, probably caused by CAL-101.

However, as of Friday the 18th, I believe (dates slip away when you are terribly ill), I was released from UC Davis because there was nothing more they could do for me that I couldn't try to do at home.

I am now not undergoing any treatment for my rapidly progressing CLL. I feel poorly and am confined to bed rest. I'm trying to get out and get some little bit of exercise, but incredibly, it has been very difficult to walk more than 100 feet without getting winded and having to sit down. I went to the local grocery store yesterday, and I had to have the bag lady help me out with a tiny amount of food. I was exhausted. By the time I drove home, I couldn't get out of the car without resting for a few minutes. My heart seems to have been weakened by this ordeal.

We are trying to get on some other desperation trial to keep me alive long enough until the ROR clinical trial starts up in probably a year or so. The odds are long, that's for sure.

No sign of transformation so far, thank the Lord.

My quality of life is poor, but I must admit I can now sit at the computer for a half-hour at a time. Paying bills and everything else is now the purview of my wife and the power of attorney for financial affairs. Thank God I took care of that several years ago!

And thank God for caregivers such as my wife. I would truly not be able to keep myself, or my pets, alive without her. I say prayers for her as well as for myself. Little did I know how dependent I am on others.

Back out of Last Hosptial Stay

2011-11-06T19:21:00.000-08:00

I spent the past week at UC Davis. Aggie college that treats more cows than people.

To say I was unhappy with the level of care I received would be an understatement. My questions went unanswered, I never did see my oncologist, I had three crazy roommates (one Mexican gangbanger type threatened me when I asked that his coughing and sneezing filthy grandchild wear a mask).

My pay was never adequately controlled even though I complained about it. There was no mention of scans for my small intestines, even though they brought it up in the first place.

And to top that off, the resident that was put in charge of my case (Dr. Beelzebub) tried to blackmail me into have an unnecessary procedure so he could practice on me before he's let me go home. And then they examined a biopsy for cancer, and when none were found there (they may indeed be elsewhere) he declared a this excellent news to be no better than a 'mixed bag'. I has what the down side was and he said because they didn't know what to do with me.

Earlier, this fresh resident he told me in in best, pump-out-chest, brining his height to all of 5-8, that I had one month to live.

I told him I didn't want to ever be seen my him, ever again. He reported my impertant attitude to his superviors, who couldn't understand why anyone would feel this way.

Dr. Beelzebub would make a fine vet, perhaps, or a pest control inspector. Wait! scratch the vet..I wouldn't want a vet like that anywhere near my pet.

As far as things go, no closer to understanding what is going on now that before. Since I'm home, my pain is adequately controlled, I'm waiting to see Kipps again.

I'm beginning to see that Churchill was right about the Soviet Union: 'a riddle wrapped in a mystery inside an enigma.'

Large Diffuse B Cell Lymphoma

2011-11-03T11:14:00.000-07:00

Transformation to large diffuse b-cell lymphoma. It's particularly troubling that there is no money for research into this affliction that affects so many CLL patients, especially since the risk is increased significantly with the use of FCR and other drug combinations that combine alkylating agents with purine analogs. This provides a potent mutagenic punch to the unstable CLL genome.

Contrary to Dr. Hamblin's glowing endorsement of FCR, and MD Anderson's love affair with the dangerous drug combination, stay away from this unless there is no other option. (Dr. Hamblin says anyone who has a serious side effect such as Richter's just 'gets the sticky end of the lollipop' a description I find insultive, dismissive, and arrogant.

For me, it's too late. but for those out there who are facing treatment decisions, choose something else. Especially with the prospect of an actual cure dangling tantalizingly in your faces.

Major, Significant Change for the Worse

2011-10-14T23:20:00.000-07:00

I am suddenly very, very ill. Over the past five weeks, I've gone from feeling pretty darn well, to being essentially bedridden.

My problem is in my abdomen. I've been to the emergency department twice, had an MRI, three stool cultures, multiple blood tests and blood cultures to look for blood infection. I've seen 12 doctors in total. They have no idea what has happened to me.

I do have some ideas. Based upon my rapid decline, one naturally thinks of Richter's Transformation. I am a prime candidate because I foolishly listened to Dr. Weirda and had four cycles of FCR. The combination of a purine analog (fludarabine) with a potent alkylating agent, is a recipe for disaster. This ups the risk of Richter's, as well as secondary myelodysplastic syndrome, which is quickly fatal.

Based upon troubling new symptoms, other possibilities must be considered. The most likely problem based on these new symptoms involves the pancreas. Pancreatic cancer, unfortunately, comes up all of the time when I analyze my overt symptoms.

I will say it could be curable, whatever it is, but it doesn't feel that way. I think many, if not most of us, have a sixth sense when something is very, very serious. That's where I am at right now.

I am going down to UCSD next week to have more of a work-up, though not too many people seem willing to go very far to get this done soon. So what I am thinking of doing, based on advice from a community gastroenterologist here in Sacramento, is to get everything looked at, not just a scan. I'm thinking of going to the emergency room right after (or before) the colonoscopy, and see if I can get admitted.

That's really the best option. The docs here in Sacramento revel that they don' think much of the medical community in this city, and I have to agree with them. That's why I go out of town for pretty much all of my cancer care.

To be honest, I will do my best to keep everyone posted as to my condition, but I may not want to share things about my body and the developments in the case.

I have no idea what this means for the CAL-101 trial. It does not seem possible that that drug could be responsible for my pain and anguish, but I guess we may have to look at everything if something doesn't pop up soon, which I think will come next Wednesday.

I do belong to a church, and the kind folks are praying for me. They will be a support network for my wife once I depart this failing planet. And she will be very well provided for once I am gone.

I'd like to make it to Christmas. We will see.

Steve Job's death

2011-10-06T10:26:00.000-07:00

The passing of Steve Jobs has affected me more than I thought. It's not that I am an Apple devotee; far from it. I own no Apple products, and I have long believed that they were over-priced. That's not why his passing has affected me.

Here was a man with more money than Midas, yet he could not beat cancer. He had the best care in the world, one would assume. He could have access to drugs and treatments that no one else could have, simply because he could have bought the drug company with promising products, outright. Yet, he could not beat his cancer.

What chance is there for the rest of us? The one who have to depend on government health care, or health insurance that is cutting back services in order to pay for millions more on the government dole. We all know it's coming, and we all know these cutbacks are being implemented as we speak. (For example, Stanford cannot come to agreement with Blue Cross because they are instituting cuts in reimbursements.)

It is a dark period in cancer research. The number of drugs approved for cancer use is declining. Vulture lawyers are trolling for patients who may, somehow, blame some past use of a drug for some unlikely outcome. Drug development costs are rising. The FDA has instituted a 'go slow' policy so that they aren't blamed for problems with drugs that come up years after approval of the drug.

Already, promising drugs for CLL like flavopiridol (Alvocidib) are being dropped because the CLL population is so small. One can only expect further degradations of health care as time goes on, and as Medicare comes under greater assault by the millions of Baby Boomers (such as me) begin to retire. As the economy continues to falter, income to the federal government, including Medicare, drops.

It's a bleak time indeed. And nothing illustrates that more than the passing of Steve Jobs. The world may have lost a visionary, but it also lost a fellow cancer fighter; one of us.

Liver numbers have gone down on CAL-101

2011-07-10T08:31:00.001-07:00

The good news is that my liver numbers, while still abnormal, are down considerably after I've reduced the dose of my CAL-101 from 3oo mg per day to 200.

The bad news is that my blood numbers are starting to deteriorate. My platelets have fallen drastically from 140,000 to 77,000. Dr. Kipps is worried and wants a new bone marrow biopsy. I told him I had one in the hospital last month. I told him I'd send him a copy (or rather, I'd ask UC Davis to send him the results). When I called Davis and asked them to fax a copy to Dr. Kipps, they offered to mail a copy to me. I said OK.

I read through the report and it's troubling. I have converted from about 11% 11q del to about 70%. Curiously, the rest of the CLL cells are positive for 13q14, which I've never seen in my reports before.

The worst part is that my cells are showing signs of 'clonal evolution' towards MDS.

The biggest mistake in my life (doing FCR based on glowing recommendation of Dr. Weirda) is perhaps coming back to haunt me. MDS is a killer, and should prevent most people from taking FCR, unless there are no other options. There were options for me, and I wish I had taken them.

In the era of CAL-101 and other kinase inhibitors, CLL may be a much more manageable disease. The CLL patient may be treated more like the chronic disease patient he is, rather than hitting him with the big guns.

Taking FCR may force mutations in the CLL cells that lead to terrible consequences. I know that Dr. Hamblin snarkily said that I 'just got the gummy side of the lollipop stick', but that flippant remark belies the terrible outcome for many FCR patients, who will die much earlier than they would if they eschewed that dangerous drug combination.

Back on CAL-101, but liver is acting up again

2011-06-21T14:58:00.001-07:00

I originally went on CAL-101 in late January, 2011. I did fine for quite some time, until April 2011. My liver enzyme numbers went up, and I was taken off the drug. I had major problems when I went off the drug. Something was going on, perhaps a sudden expansion of the lymph nodes that began pressing against internal organs, or perhaps my small or large colon. I was in a lot of pain. Luckily that went away, but I felt poorly for the next six weeks. My liver numbers were stubbornly high.

Then I went into the hospital with zero neutrophils. I was there for five days.

I was able to go back on CAL-101, but at a reduced dose. I've been on the reduced dose for about three weeks.

Unfortunately, my liver is acting up again, and my white count has fallen again, as have my neutrophils. It may be that I'll have to go off CAL-101 because of side effects of the drug, and because my blood numbers are going in the wrong direction.

The saga never ends, apparently.

In, and out, of the hospital

2011-06-04T10:31:00.000-07:00

A week and a half ago, I was beset by vomiting and nausea. I was initially sick to my stomach. My wife helpfully suggested that if I just throw up, then it would be over, and I could get back to sleep.

Big mistake! I did force myself to throw up, but then I couldn't stop. I also couldn't keep even a tiny sip of water down. I would vomit more fluids than I was taking in. Obviously, that is dangerous. I was rapidly becoming dehydrated. So at 7 am I went to the hospital's emergency department.

Well, they solved the immediate problem by giving me fluids intravenously, which I expected, and by giving me IV Zofran and Atavin, which makes sense, and then by admitting me, which I did not expect, nor want. They did so because my absolute neutrophil count was at zero, again.

This was a surprise and a disappointment, especially since I had a neulasta shot a week before that. It apparently made no difference, for reasons I will discuss later.

So I spent the next five days in the hospital. This being the US, I had just one roommate. (In the UK, there are up to six patients to a room, even those dying of cancer or heart disease.) He had had pneumonia for three months, and was in the hospital for those three months. He was released while I was there, and I'm sure he was happy he got out.

After my roommate left, I had the room to myself, which was nice. No sharing of the bathroom, nor sharing his germs with me, especially with no neutrophils.

After some manipulation, my counts did begin to rise, sufficient to get me out of the joint. I never really exhibited any signs of illness after that first terrible day. My lungs were clear, apparently, with no fluid in them. But I did get Netflix to work, and I watched some cool History channel programs on military history. Nice. But boring.

Except...for the bone marrow biopsy they wanted to do. Actually, the two they ended up doing.

UC Davis, where I was, is a 'teaching hospital'. Meaning that they take people off the street, give them a few lectures, and then a scalpel, and turn them loose on unsuspecting patients.

The first biopsy was excruciatingly painful. I mean this must be what operations were like a thousand years ago, except without the alcohol making you drunk enough to deal with the pain. And what pain! Apparently this woman (girl) junior doctor decided to go into my bone from weird place (the real doctor told me that he 'wouldn't have chosen that spot to do the biopsy', which is medical-speak for 'what the hell was this woman (girl) doing????). All I know was I was screaming in pain, telling the woman (girl) that I couldn't stand the pain. She then said, and I quote, they could go get someone who had done biopsies before. I said, of course, THEN DO IT!!!

This new woman (girl) did an OK job, though it was still painful.

These two biopsies made number 19 and 20. Is this some sort of record? The kind of record you don't want to have, ever?

My marrow turned out OK. I just have CLL. That's a big relief!

So, they let me go.

Now, what about my neutrophils? Did I have a zero count? How could I survive without being sick if I had no neutrophils???

My neutrophils may be hiding in the tissues, as Dr. Kipps has surmised. The CAL-101 pushes lymphocytes out of the lymph nodes and back into circulation. In my situation, the neutrophils are there, and are being produced (as the biopsy shows), but they just aren't getting into circulation in decent numbers. But, they apparently are there. I don't understand it, and I don't know if anyone understands what is going on, really.

It IS troubling that the Neulasta did not raise my neutrophil levels within the week. Perhaps it was responsible for boosting the neutrophil counts while in the hospital. Perhaps it was the niacinamide I took (though that didn't work to increase the totals in the week leading up to the hospitalization). Things aren't all peachy in the health department, not by a long-shot.

But...I am out of the hospital and doing OK.

And...I'm back on CAL-101! That will ensure (at least for a while) that my WBC increases as the CLL and other lymphocytes are booted out of their happy homes in the lymph nodes, where they grow in happy little colonies, cheerfully killing their host.

I'm on a lower dose. I'm saying my prayers that my counts hold, and my liver numbers stay on track. It took a while for Stanford to get to this point (original estimate, one week off CAL-101; it took me about six weeks in actuality to get back on the drug).

Next step, GET CAL-101 APPROVED so that everyone can benefit from this drug. I think it is keeping me relatively healthy. I just hope it continues. Dr. Coutre has been very helpful in getting me on this drug, and keeping me on it. Thanks!

Now, crashing neutrophils

2011-05-10T12:50:00.001-07:00

As I tell my wife, if it's not one thing, it's another. Seriously. I have a new health complaint everyday. Sometimes it's a sore foot. Next day, a painful back. The next, pain in my abdominal nodes. And the next, a headache.

Occasionally, I have a good day. That is a bad thing. If I go through the day, and say to myself, you know, I had a pretty good day! In fact, I feel fine! How nice!

That means I will be in the hospital the next day. No good day goes unpunished for me. I'm serious. This ALWAYS happens. ALWAYS. Without exception. EVER.

I had a good weekend. I felt kind of tired Saturday, but I got the truck out and finally clean out the pile of stuff the gutter guys left when they re-did my gutters. I told them I'd dispose of things if I could get a cheaper price.

Sunday, another good day. Church was nice. By Sunday afternoon, I thought maybe I had crossed the creek. My painful nodes were history. My fever was over and done with. I had lots of energy and got lots done.

Never tempt fate.

The next day, I got a copy of my lab results from Friday. They show 2% neutrophils. That's not good when your WBC is 4.4. Doing the math, that means my absolute neutrophil count is about 100. Way below the 500 cut-off for serious neutropenia. It's at the same level that I had when I was in the hospital with a 105 degree fever. It's tied for the worst I've every had.

I'm off CAL-101, and I think they are trying to ditch me from the trial forever. Stanford wants me to tell them that I've progressed on CAL-101, but I don't know if that's true. I know this latest blood work suggests that my CLL has skyrocketed, but I've been off CAL-101 for almost three weeks.

Listen to your body. If it is telling you that you are doing well, you are in big trouble.

Off CAL-101 and suffering

2011-05-05T19:52:00.000-07:00

Two weeks ago, I went to Stanford for a routine medical appointment. Dr. Coutre was not there, so I saw another doctor.

After the three-hour drive home, I got a message from the clinical trial coordinator that my liver enzymes were elevated, and I must stop taking CAL-101. The coordinator explained that this is not uncommon, and most everyone who has elevated liver enzymes goes back on the drug at a lower dose. (I've been on 150 mg, twice a day.)

Well, it wasn't that simple. My lymph nodes started increasing in size in a couple of days. (CAL-101 works very, very fast in reducing the nodes; it apparently works just as fast in the opposite direction.)

Anyway, by Saturday night, I was in agony. My lymph nodes apparently started pressing on this organ and that. I also spiked a fever. So I went to the ED. They released me after prescribing Levaquin (sp?). By Monday night, I was in poor shape again, and went back to the ED. They did not admit me (yay!!!), and I went home.

I had my liver enzymes tested after one week. The enzymes had not gone down to a normal level.

Meanwhile, two weeks after going off CAL-101, I am very unhappy. I have massive nodes again, I have significant fatigue (starting on Wednesday) even though I am sleeping well for about seven hours a night, which is normal for me. The sleep does not seem to refresh me.

I've faxed the blood work to UCSD, Dr. Kipps' nurse. That was a week ago. Silence.

I did get a call from Dr. Coutre yesterday, which was nice. He wants me to wait several more weeks and then evaluate what has happened to me.

I am very disappointed, of course. My lymph nodes went down fast, and stayed down. I felt great. My blood numbers were OK, and things seemed to be going as I had expected. Now, I am in a bad place.

I think the ideal would be to stay on CAL-101 at a lower dose. I don't know if that will be offered.

So, I'm back in the CLL misery.

Flavopiridol, One Year Later

2011-03-26T07:39:00.000-07:00

I went down to San Diego for my one year check-up after my eight-month trial with flavopiridol (Alvocidib).

I had a very good response to the flavopiridol. I was hospitalized overnight for the first two courses, to make sure my potassium levels did not go overboard as a result of tumor lysis syndrome (although the kidneys can be damaged from the products of CLL cell necrosis, tumor lysis is a nice thing, since it means the evil CLL cells are blown apart by flavopiridol).

My rock-hard abdominal lymph nodes gradually softened and melted away using the drug. This was accomplished by weekly infusions in San Diego, for four weeks in a row, with a two-week holiday in between cycles.

As I've noted here, the drug was not an easy drug to take. The main problem was with the urgent diarrhea that followed a hour or so after the drug, and that lasted through the night. The other side effects I noted were general malaise, about two hours of abdominal cramping and pain, and a fatigue that lasted a few days.

The other, perhaps more serious side effect, was the neutropenia that accompanied the drug. I had to have either a Neupogen series, or a Neulasta shot about once every couple of months. Of course that may have been also linked to my disastrous dalliance with the hated FCR.

If they could develop a version of the drug that didn't have the diarrhea problem, they'd have a winner. Or if it could be administered locally, so I could get home and sleep off the problem, it would be better. (Obviously if the drug was approved, this latter condition could be met.)

My response lasted about the nine month average noted in previous patients. My feeling is that perhaps Flavo could be given for six months or so (since I didn't note any more lymph node softening or reduction in size after that), and then monthly. It's an unpleasant drug, but if it could keep the CLL at bay, I'd gladly do a monthly 'maintenance' dose.

Of course I have no idea if that would work, but that might be a winning idea, even with the drawbacks. Flavopiridol is an excellent drug, it works just as well for a second go-around (rare in any cancer drug), and it has few (but annoying) side effects.

I wonder about its fate as a approved drug. It is effective in over 50% of CLL patients, and in patients who respond, the outcomes are good. But it isn't a cure, nor a lasting treatment, unless it could be given as a maintenance drug, perhaps.

Mixed Results

2011-03-20T08:08:00.000-07:00

I'm through with the rituximab infusions that have accompanied the CAL-101 daily pills (150 mg twice a day).

CAL-101 pushed many CLL cells out of the lymph nodes and into the blood. My WBC which has been hovering around 2.1 after a disastrous bout with FCR, went up to about 47,000. It has dropped to 24,000, where it has stubbornly stayed.

I've also had increasing fatigue and a few bouts of day sweats, both of which I associate with CLL progression.

We know that CAL-101 is not a cure. A recent paper that will be presented at ASCO paints a dismal picture of the drug, with only a 33% response rate. It shows that many people drop out of the trial after disease progression. And lymph nodes decreased by only 50%, which means that CLL, which grows primarily in the nodes, is still present in large numbers.

It may be that drug resistance to CAL-101 is more common than we had all hoped.

We are all hoping for a solid treatment that is easy to tolerate and keeps the CLL at bay, if not curing the terrible disease.

As it stands now, it doesn't look as though CAL-101 will be that drug, at least in the population of heavily pre-treated patients such as myself. Perhaps it will do better in untreated patients.

I must admit that it will be great if it works extremely well in untreated patients, but not well in others. It would be bittersweet for us who have been through the mill with CLL.

I've often wondered about the elation of CML patients (chronic myeloid leukemia) who saw the miracle treatment of Gleevic and related drugs, but failed to respond themselves. The elation, and then the crushing disappointment must have been terrible for them.

For now, my lymph nodes seem stable.

CAL-101... A week later

2011-02-03T08:20:00.000-08:00

I had my second infusion of rituximab yesterday at Stanford. I'm happy to report that the infusion went well; no vomiting and no chills, as happened a week ago. My GERD is back; I assume this is due to the vomiting and/or the rituximab infusion.

My blood numbers were interesting. Since my disastrous bout with FCR, my counts have been very low, with the WBC ranging from 2100 to 2700 or so. This time, my white count is over 44,000. This fits with what I've learned about CAL-101, and also fits with my sudden and unexpected shrinking of my lymph nodes. The thinking is that this kinase somehow pushes CLL cells out of the lymph nodes and into the circulatory system, where it can be detected by a simple blood draw.

The rest of the numbers are about what I've been living with for the past few years. My hemoglobin count is a bit lower, from the high 12s to the high 11s. My platelets, though, are much higher. They've been hanging around the 90 neighborhood; now they are over 140, and in the normal range. This is the first time that's happened in years and years. In fact, I can't remember when it was in the normal range.

My absolute lymphocyte count is high, as one can imagine. My absolute neutrophil count is also up substantially, which is very nice. Dr. Kipps has been puzzled by the low neutrophil counts over the past two years, which have nevertheless not led to a single serious infection. He thought that maybe the neutrophils were 'hiding out' in the tissues somewhere. It appears that he was right.

I am taking 150 mg of CAL-101 twice a day since Wednesday of last week. It's not a difficult thing to remember, and I'm home in the morning and evening. I'm back on acyclovir and Septra, the first to forestall herpes infections, and the second to help prevent bacterial infection, primarily in the lungs.

I'm carrying on my normal activities, which include having a sewer and water line replaced at my rental house, and doing some painting and other minor repairs. I'm trying to stay away from sick people, crowds, and soil fungus.

So far, so good.

Surprising Results

2011-01-28T08:18:00.000-08:00

I took my first dose of CAL-101 on Wednesday at 1:15 pm. I then had my rituximab infusion, which I covered in my previous post.

I didn't write yesterday about my surprising results from CAL-101. Thursday morning, when I woke up, I noticed my abdomen seemed noticeably smaller. Hmmm, I thought. This seems very sudden of a response. Dr. Coutre told me that I would experience results quickly, within the first week, but in 18 hours? This seems on par with flavopiridol, which has a tremendously fast and potent kill effect, so much so that one is hospitalized to keep an eye on one's potassium level, so it doesn't get out of hand and destroy one's kidneys (one of the first patients on flavopiridol (Alvocidib) died from acute renal failure in Dr. Byrd's study).

I'm not sure what is going on in my potassium level, but I am staying well hydrated just to be on the safe side. And I've not heard of anyone dying so far on a CAL-101 study, so that's reassuring. (However, one must realize this is a clinical trial, and sometimes significant side effects are found long after the drug has been used in patients.)

This morning, my gut is smaller still. Amazing. I would never have believed it. It's like magic. It's like I've had liposuction on my nodes.

I must say that my other enlarged nodes are not following quite the same path. Perhaps it works on massive nodes more than slightly enlarged nodes.

Of course, time will tell and I know this is not a cure. But I wonder if CAL-101 could be used in emergency situations when lymph nodes get out of control and start impinging upon organs.

I have recovered pretty much from the unpleasantness of Wednesday's rituximab infusion. I am constipated, though, something that rituximab does to me, that they don't tell you about. (In my first go-around with rituximab, I was so constipated I thought I might be plugged up forever. It was terrible. I used a stool softener this time, though obviously not quite enough.)

Well, I must say that CAL-101 works unlike what I expected. And it's illustrated that much of my gut was enlarged lymph nodes, though they have never gotten as bad as they were before flavopiridol. Flavopiridol was what I needed when I took it a year and a half ago. It was more troublesome than CAL-101 is so far (we will see what the future brings), but I was pretty bad off. And the fact that Dr. Kipps had that trial was fantastic.

CAL-101

2011-01-27T21:36:00.003-08:00

I have made the cut, I guess you could call it; I'm now in the Stanford CAL-101 trial, combined with rituximab.

This is a trial of weekly rituximab infusions, for eight weeks, combined with 150 mg of CAL-101 twice a day. The CAL tablets come in a prescription bottle, with a seal and, yes, even cotton at the top of the bottle. The nurse said that they have a drug company bottle the CAL for Calistoga.

I went in for imaging on Tuesday and Wednesday of this week; I had the CAL that afternoon, followed by 375 mg/m2 (the usual dose). I've had seven rituximab infusions before, with no problems.

This time was different. I don't know if it was the long day (up at 5:30 to get the MRI by 7:00), the MRI contrast (I was in that darn machine for over an hour), the CAL, or what, but at the 7/8 mark, I started to get nauseated. Yep, I threw up my day's gorp trail mix, bananas, and Gatorade is a disgusting mix. Two sets of multiple vomiting episodes. The first I didn't quite make it to the bathroom. I tried to hold it, but dragging a IV pole along for the ride didn't help. (I'm sorry, Ms. Housekeeper. I really am.)

I felt pretty rotten. I also got a bit chilled, but my blood pressure and temperature held at the normal level. I tried to tell the nurse practitioner this, but she was very Nurse Ratchet about the whole thing and stopped the infusion. I told her I didn't feel good and wanted to go home (home being a three hour drive). We compromised with her re-starting the infusion, and me promising to stay the night (at another $112) in super-expensive Palo Alto. (BTW, near Stanford, the lodging is even more expensive than La Jolla!)

The nurses made the reservation for me, which was really nice. I'm sure my green complexion motivated them, and since it was after 8 pm, they wanted to go home as badly as I did.

I got to the motel, locked the door, turned the heater on full blast, and promptly fell into a very deep sleep for five hours. I even fell asleep before I could floss and brush my teeth.

I felt much better when I awoke, though I had a splitting headache. That vanished by late morning. I putted around the motel (actually I watched an episode of The Sopranos. I've never seen the program, because I'm very put off by violence). This was on USA or some other network, so some of the violence was cut out. Still more violent than I wanted, so I changed the channel.

It's late evening, and I feel OK. However, with rituximab, I now need to be extra careful about avoiding infection. My numbers have been OK the past six months or so, and I've gotten out of the habit of being really vigilant. That has to change. Bummer.

Intermittent Problems

2011-01-15T10:20:00.000-08:00

I've been doing OK the last few months, but I've noted an increasing sense of fullness in my upper abdomen. I sense the CLL is growing again in my gut. Not good. Plus I've had an occasional problem with nausea and other gut-related maladies (indigestion, GERD, and diarrhea).

I see Dr. Kipps later this month. He indicated to me in September that he wanted to keep a close eye on the lymph nodes, but concluded that I didn't need treatment at that point. My last appointment was in late November, and he felt the same way.

Options include Mozobil plus rituximab, CAL-101 plus rituximab, or revlimid with rituximab. We will see.

Oh, by the way, I've had my 17th bone marrow biopsy. Even with percocet, it was still painful. I wish things were less painful. Interestingly, my blood pressure went from 118/60 to 135/70 just before the procedure. Not surprising, since I've had lots of pain before.

Another New Year

2011-01-01T10:16:00.000-08:00

As one gets older, it seems that the passing of the year goes by faster and faster, doesn't it? My wife and I stayed home. The weather being wet and cold, the noise level for the celebration in the neighborhood was a bit subdued this year, though that isn't anything I'm complaining about.

I have been having some increase in symptoms the last week. I've had a couple of days of feeling pretty full, which must mean the nodes are growing again. So, nine months after the end of my eight months of treatment with flavopiridol, I am going to need more treatment.

I did go to Stanford and met with Dr. Coutre regarding a CAL-101 trial, this time with rituximab. That was in September. One concern I had was having a CT scan as part of the trial, which I won't do unless I'm in immediate danger of dying. He assured me that he could substitute an MRI, which is less dangerous for the patient.

Well, since then I did sign up for the trail, but the trial coordinator, Michelle, said the MRI is off the table. She did want me to do the three-hour drive to meet with Dr. Coutre again, but I told her I'd like to avoid that if possible. I was down there just a couple of months ago.

She was inflexible, and said she talked with Dr. Coutre, and that he has changed his mind, or perhaps the drug company is now inflexible about the scanning. Too bad. I told her to give up my space on the trial to someone who doesn't mind being irradiated with a lifetime's worth of radiation.

So, I have to resign myself to not trying one of the new 'great' drugs. And of course it will be another four or five years before the drug is approved, if it is.

I wish I had not placed my hopes in CAL-101. (Besides, the response rate is only about 50% anyway, so it may not have even worked. And that I would have had a series of CT scans?)

Holiday Season Update

2010-12-20T10:08:00.000-08:00

It's actually a bit hard to tell where I'm at vis-a-vis CLL. I feel OK, but my nodes are slowly growing again. Since I'm at the average response period after flavopiridol (Alvocidib), I should expect these events, I suppose.

My energy level is high and I'm able to work full-time on my own business (since retiring from the State of California). Like a lot of people, I find I'm busier now than when I worked. (Why? When I was working, I just put things off that I couldn't get down. Now I am able to load those tasks onto my daily plate.)

I have not felt sick, and believe that flavopiridol could very well find a place in the doctor's bag of therapies, especially in end-stage CLL patients such as myself. This drug has worked in this 11q del patient who has failed HDMP+R, ISF-35, and FCR.

In any case, I am casting around for something else to do to keep the CLL monster at bay. I personally have given up on a cure (since it doesn't exist, except in the rare case of a long-term transplant patient who survives that ordeal). I'm looking for long-term control, if I can get it.

I suspect that I'll either choose Revlimid+Rituximab or some version of CAL-101 or the new PCI-32765, though currently that trial is often limited to those 65 and older, which I'm not.

There are a number of good-looking candidates for more benign treatment of CLL coming down the pike, but cures they are not. Long-term control in a disease of (usually) the elderly might be enough, though I suspect that Drs. Kipps and Keating don't want to end there.

Have a nice Christmas and New Years'. I can't believe this year is almost over...

Happy Thanksgiving

2010-11-25T09:02:00.000-08:00

Another Thanksgiving has come. I hope all have a blessed and wonderful day of thanksgiving. I'm personally thankful that my wife is recovering and getting better every week. I'm doing OK. My counts are still below normal because of permanent damage caused by my stupid foray into FCR-land.

I had a severe inner-ear infection a couple of weeks ago. It seems to have abated, but it's left me with a nasty cause of tinnitus. For those who have been lucky enough not to have experienced this 'ringing in the ear', it's a constant (in my case) high-pitched buzzing, caused by long-term exposure to loud noise (not my problem) and infection.

It's very annoying, and it's accompanied by hearing loss. I have an appointment in January with the ENT doc, but there's nothing they can do. Medical science has a long way to go.

Anyway, hope things are better with you all. Be thankful for what we do have.

Survived Halloween

2010-11-05T18:55:00.000-07:00

Halloween is my least favorite holiday. I dislike being tied to the house, waiting for teenagers to show up after 9 o'clock for a freebie. I also dislike the trend for parents in their thirties to hold out a bag for themselves after their tiny tot has gotten a treat.

We had over 65 trick-or-treaters this year, down from about 150 last year. I had one woman confess that she drives over to our area from hers, because it's 'safer and has better candy'. At least she's being honest. I've long suspected this, because there are only about 30-40 children in the two blocks around ours, and they don't come around twice.

Anyway, I'm holding my own. My ear infection has improved, though the antibiotics have interfered with my digestive system, reminding me of the days a year ago when flavopiridol did much the same (though to be honest, it was worse with flavo).

I'm shopping around for another treatment to keep my CLL in check. At this point in time, I think that that is the best we (and especially) and I can hope for.

Have a great holiday season, folks. By this time next month, I'll probably be involved in yet another clinical trial.

Steady as she goes

2010-10-23T09:32:00.000-07:00

Saw Dr. Kipps on the 19th. My CLL is holding steady. My lymph nodes, which popped up a bit before the last visit in September, are now about the same size. Obviously I still have CLL, and it still is active, but luckily it is behaving itself, and not creating too many problems now. (Actually, not any problems that I can see. My energy level is back up to where it was before flavopiridol, and I've not had any infections or other complications. So I now have a six-week reprieve.

Counts are still terrible because of my disastrous dalliance with FCR. My marrow is permanently ruined. As bad as that is, it also limits my choice of further treatment. Counts have to high enough (especially neutrophils) to successfully sign up for clinical trials.

I do have a minor ear infection that I'm getting antibiotics for. One of the many annoyances (let it stay minor!!!) that come with CLL. You just can't fight off infections well.

The past month has been a good one, for me.

Wife in Hospital in Critical Condition

2010-10-09T05:53:00.000-07:00

My wife is in the hospital, in critical condition, with severe asthma. She's in a medically-induced coma and on a ventilator. This is the fourth time this has happened in the past five years.

She's stable with her most serious form of asthma most of the time, except when she comes down with a cold. Then it's a fight to get her through it. About half the time, she can throw it off without going to the emergency department, but sometimes she can't. This is one of the latter times.

It's especially difficult when one couple has both with serious medical conditions. So far, when I've been really ill, she's been healthy and able to take care of me, the house, and the critters we include in our furry side of the family. This time, she can't do anything, obviously. I'm healthy enough, thank God, to pick up her responsibilities, but she does a lot, and I gain a new appreciation for how helpful she's been in the quotidian responsibilities of running a house.

Unlike me, who has always been a worrier about my health, she hates going to the doctor. That's bad, because with crashing asthma, she needs to have regular visits from her doctor. She hates the current doctor she has at UC Davis. As this crisis started to unfold on Monday the fourth, I put in a call to Davis to get her an appointment with a different doctor. They told me I couldn't change her doc. I asked to speak to a supervisor. Unfortunately, the supervisor called my wife and not me, and she told them she didn't want to see the doctor.

I suppose she avoids the doctor for two reasons, the doc's attitude and for cost reasons. The latter shouldn't be a problem, because our Blue Cross plan picks up 80 percent of most costs, and the only fee for a doctor's visit is the co-pay. However, this doc runs up thousands and thousands of dollars for 'tests', which except for the blood work, never seem to get done. And he is abrasive, and is very judgmental as to how my wife is managing her asthma.

The doctor she likes is with Kaiser, the plan she used to have. She has seen him occasionally over the years, and he was available through UC Davis, but I have no idea where he is now.

She now we wait. She has a son and a daughter. Her daughter has the power of attorney for health care issues, which is unfortunate because she's one of those people who haven't had a lot of experience with medical issues, and tends to slavishly follow my wife's blurted out thoughts that she would rather be dead than 'hooked up to machines'. What doctors know all to well is that when people are suddenly in the position of needed a machine to stay alive, the patient will almost certainly take the route to staying alive. The will to live is strong in most of us.

She's told me in the past that she didn't want to be ventilated again. However, at Kaiser emergency department, when she couldn't breathe, she did not refuse to be intubated again. That explains a lot about her thinking. Yet I'm afraid if she needs, for example, to have a tracheotomy, her daughter will refuse because she thinks she understand what her mom wants.

A similar experience occurred with my own mother. She apparently told my dumb sister that she never wanted to be 'tied to machines'. When she was on a ventilator herself, and the doctors said she needed a tracheotomy to help wean her off of the ventilator. My stupid sister refused. I hired an attorney to sue my sister to remove her from being the attorney-in-fact for medical issues. The hospital was in an uproar. They solved the problem by slowing bringing my mom out of her sedation, and asking her herself. My mom nodded 'yes' when asked if she wanted a trach. When people are actually faced with the immediate situation they feared, they tend to chose life.

I really, really hope I don't have to fight her daughter to save my wife's life. That ruins relationships for good.

If you are a praying person, and want to say a prayer for my wife, I would appreciate at it. Her name is Tonniette or Tonia for short. We would both really appreciate it.

It's difficult being the caregiver for a change.

12 year anniversary

2010-10-05T07:56:00.000-07:00

I suppose we have several anniversaries to keep track of in our lives. Wedding anniversaries, the start of a business, milestones for your kids.

CLL patients keep track of another anniversary: their diagnosis with CLL.

Twelve years ago, I felt a large lump in my neck, on the ferry from Vallejo to San Francisco. I had planned a nice day in SF as a reward for nine months of hard work renovating an older house I had purchased some years earlier. The house was a wreck, and needed new plumbing, electrical and structural work. But, I finally got the job done.

That lump, of course, turned out to be CLL. At 48 I joined the millions world-wide fighting cancer.

I was, (and am) the type of person who needs to know as much about my disease as possible, especially the treatments available that could rid me of this cancer. That's when I first encountered the word 'incurable'. I can still remember when I read that CLL had no cure; it was in my driveway, reading a long review article about CLL from Leukemia & Lymphoma Society. Not a pleasant word to read.

Of course, 12 years ago, there were fewer options for treatment than there are today. It's odd to look at it this way, but patients diagnosed now have a much brighter outlook than those diagnosed a dozen years ago. I wish I could have postponed my disease a decade, or more.

Back then, chlorambucil was the gold standard to treat CLL. It wasn't a cure, and complete remissions were rare. Fludarabine had come onto the market, and a year earlier, something called rituximab was approved by the FDA. It would take a while to sort all of this out.

I joined the CLL group that GrannyBarb started, read as much as I could, and tried to become a patient advocate. I flew to Washington, D.C. two years running at the behest of the Lymphoma Foundation of America (now the Lymphoma Research Foundation) to lobby my congressional representatives for more funding for this all-too-common disease. Everyone was sympathetic, and we have maintained good funding for the disease, especially through the latter years of the Clinton administration, and the early years of the Bush administration. (September 11 certainly took the focus of the federal research community away from ordinary research and turned it towards research on bioterrorism.)

A couple of years later I consulted with Dr. Thomas Kipps at the University of California, San Diego. His name kept popping up in the research I was continuing to do on the disease, he was in-state, and my insurance would cover a visit (although I'd gladly pay out-of-pocket to consult one of the best CLL minds in the world).

There I learned that I was unmutated, ZAP-70 positive, 6q deletion, and had a high Beta-2-Microglobulin and LDH level. Couple that with the fact that I am male, and young for a patient, and I realized that I had been dealt a poor hand indeed.

Yet I avoided treatment for eight years. I tried any non-chemo therapy I could, including zinc to lower the amount of copper in my body (copper promotes angiogenesis, the growth of new blood vessels), resveratrol, EGCG, and Chinese herbal medicine.

Dr. Kipps and I concluded that treatment was indicated when my absolute lymphocyte count (ALC), which had been boringly stable (though elevated, about 30,000 as I recall), took off like a rocket. We waited a few months to see if it was real; the increase was.

I decided on high dose methylprednisolone plus rituximab for my first treatment. Dr. Kipps likes clinical trials, and I was game, so I decided on that for my first treatment. I got in on the trial of high-dose rituximab with the steroids. Unfortunately, because of red tape, I had to wait almost a year for the trial to start (September 2006). In retrospect, that was a mistake. I've come to believe that the time to start treatment is when there is a change for the worse in blood counts. Unfortunately, after that treatment, my status changed to 11q deletion, which carries a 'grim' prognosis. That was in 2007.

So how do I feel at 12 years? I feel OK. I've had a number of other treatments, of course, all associated with clinical trials. The last treatment, flavopiridol, was quite effective; it took my enlarged abdominal lymph nodes way down, almost to normal. I'd do that one again, though the side effects were inconvenient to say the least. My experiences with that drug are detailed in this blog. In spite of the difficulties I had, I had a very good response. My abdominal nodes had grown the size of a small cantaloupe, and was quite uncomfortable. And the drug drove the 11q down to 11 percent of my CLL cells, which is good.

What's next? Dr. Kipps is worried that the CLL has started to make a re-appearance only six or seven months after the end of my treatment (11q patients only have a nine-month remission, on average. I had even less). So I am exploring yet another clinical trial. He's also concerned that my blood numbers may indicate further genetic mutations that indicate perhaps myelodysplastic syndrome or something else. Dr. Coutre at Stanford has explained the FCR I unfortunately took has 'chewed up' or 'beaten-up' my bone marrow, probably permanently. This complicates the picture.

My spleen and liver remain normal sized, at least at present. And the lymphocyte count remains low (too low, in fact, thanks to FCR).

So, like always, we have to see what happens. So far, I've avoided most hospital stays, apart from the five days after the first dosing of HDMP+R, and an infection and fever a year later.

For that, I am thankful to God and modern medicine. I know my time on this planet, like everyone's is limited. We all get voted off the planet, eventually. I'm very glad I've been able to hang around here longer than I thought possible, given my negative markers.

The latest

2010-09-17T11:48:00.000-07:00

Saw Dr. Kipps on Tuesdays, the only day he pretty much sees patients. I had some CLL friends in San Diego who were very nice and ferried me around a bit, picked me up from the Cancer Center and helped me get around. Also, they took me out to dinner at a place called Milton's. It's a Jewish-style restaurant in La Jolla. It was very good; the pastrami was excellent. I had a soda called Dr. Jones (I think) and it's apparently a NY classic that you just can't get many places. It was good and made me feel a bit of a connection to NY, which I've been to exactly one time (to see an herbalist who cured one man of CLL, though no one else, to my knowledge).

Dr. Kipps is worried about me, since my counts are still in the tank. He suspects something else is going on. He wants me to start treatment again, giving me four different trial consent documents. Combined with re-doing flavopiridol or Cal-101 at Stanford, that makes six different protocols. That's if my beaten-up marrow has not transformed. He seemed pretty worried, and gave me a hug.

The bone marrow biopsy was pretty painful, even with the percocet I insist upon. (That was a problem in itself; Dr. Kipps apparently forgot to send the prescription over, so his nurse had to track down this busy man, and get him to write a script.)

So I am now waiting and worrying over what this latest biopsy will show. He said my last biopsy in May was fairly normal, and he doesn't understand why my counts are so terribly low (especially the white blood count) when the marrow looks OK.

There may be something else going on...

My Marrow has been "Chewed Up" by FCR

2010-09-14T05:48:00.000-07:00

I saw a CLL doctor for yet another opinion, this time a doc at Stanford. We discussed my situation, especially in light of Dr. Kipps' recommendation that I start a search for a donor for a much-feared stem cell transplant (the survival figures are not as high as I'd like).

I had to wait over an hour to see him, which seems to be par for the course for busy CLL types. I gave a brief rundown of my history, and the fact that I've had four treatments; HDMP+R, ISF-35 (direct nodal injection), the idiotic FCR, and flavopiridol. According to his labs, the slight improvement in my numbers noted at UC Davis has disappeared, but I think some of that can be ascribed to different labs. I like Davis' lab, because I always have better numbers there.

He said there were two drugs in trials at Stanford that he likes for CLL: Cal-101 and another drug that he didn't even mention the name/number of. Something like PCI something or another. I'd pass the name along, but he didn't pass it along to me. (Searching the web I do find two candidates: PCI-32765 & PCI-45292, both Bruton's Tyrosine Kinase inhibitors.)

We then talked about why my marrow has never recovered. The doc said my marrow was 'chewed up' by FCR. I asked if there was anything I could do to make it better. He said, 'no'. He also said, 'they never mention that when they publish glowing reports about FCR.'

So, in addition to a heightened risk for Richter's tranformation, and myelodysplastic syndrome, our non-friend FCR can 'chew up' your marrow. Wonderful. Apparently, FCR has left me with a permanently scarred and chewed up marrow. Sweet!

The doc is going to send me the protocol for Cal-101, which he seems to like a lot. It apparently doesn't give many people a complete remission, but it does help shrink swollen lymph nodes.

Besides my chewed up and spit out marrow, the abdominal nodes may or may not be making a comeback, so this might work well. We will see. I see Dr. Kipps soon as well. And, joy, I get another bone marrow biopsy! That will make number 16. I wonder what the record is? I wonder if I have any marrow left in my hip after all of the sucking and drilling?

Holding my own, but problems may be ahead

2010-09-06T11:53:00.000-07:00

I saw Dr. Kipps in mid-August. He was harried as usual; I had to wait an hour and a half. I don't know why he gets so backed up; I suppose it's partly because they fit people in as the need arises.

He started out by telling me my May bone marrow biopsy was good. I had a nodular partial remission, which is better than a partial remission. I still have CLL cells in me, but they are not so widespread. So the flavopiridol worked quite well. He was happy with my performance and over-all activity level.

However, he became concerned when he saw my blood numbers. They still haven't recovered from the FCR two years ago. He seemed disturbed by the numbers. He wants me to come back in September for yet ANOTHER bone marrow biopsy. My pelvis is more holes than bone, now, I think. This will make number 16 I believe. I'm a pin cushion.

He also mentioned that he wants to start a search for a stem cell donor.

As you can imagine, this was extremely disturbing news. I was certainly prepared to re-do flavopiridol if the drug company would allow retreatment (another 13-14 months of decent quality of life sounds EXCELLENT to me!!!). I suspect he thinks that things have gotten past that now.

It's all due to the FCR in my mind. My counts are still way low, and have never come back up.

The transplant, of course, it a sure death sentence. Few people my age make it more than a couple of years. No one I know, even through the internet, has survived more than five years. It's a terrible procedure that over-all, doesn't work. Up to 40% of patients don't even get out of the hospital. It takes a full-time commitment by a caregiver, and my 'caregiver' has a chronic disease herself.

Since I live in Northern California, I'm going to get a second opinion at Stanford. They have a decent CLL practice there, and they also do transplants.

A transplant is a last-ditch effort to keep you alive for a few more years. It just depends on how much agony (graft-v-host disease) you want to endure, and how your cancer responds to the graft. It also depends upon getting your disease down to a low point, at least a complete remission.

Getting to that point would present a problem; I've never had a complete remission in this disease.

Bad news all-around. This may be my last Christmas (if I make it that far).

OTOH, no one is guaranteed anything on this planet. It's just bad timing. Treatments for CLL are really getting a lot better, and promise to get better all the time. Just not soon enough for those of us with intractable cancer.

Medical Rationing Begins

2010-08-15T23:59:00.001-07:00

I HATE to see stories such as this:

Medicare Says No to Stem Cells for MDS
By Charles Bankhead, Staff Writer, MedPage Today
Published: August 06, 2010

WASHINGTON -- Medicare patients with myelodysplastic syndrome (MDS) will receive coverage for allogeneic hematopoietic stem cell transplantation only when participating in qualified clinical trials, the Centers for Medicare and Medicaid Services (CMS) has ruled.

CMS decided against coverage because available evidence "does not demonstrate that the use of allogeneic hematopoietic stem cell transplantation improves health outcomes in Medicare beneficiaries with MDS."

However, the agency also ruled that allogeneic stem cell transplantation is "reasonable and necessary" for MDS through the Coverage with Evidence Development provisions of Medicare regulations. As a result, Medicare beneficiaries can qualify for coverage of therapy provided through clinical trials that meet certain criteria.

CMS will consider only prospective clinical trials that examine allogeneic hematopoietic stem cell transplantation's effect on the outcomes of relapse-free mortality, progression-free survival, relapse, and overall survival. Trials must address one or more aspects of three questions:

* How does transplantation affect outcomes in Medicare patients with MDS as compared with no transplantation?
* How do the International Prognostic Scoring System score, patient age, cytopenias, and comorbidities affect the outcomes?
* What characteristics of treatment facilities predict clinically meaningful improvement in the outcomes?

The complete text of the CMS decision is available at http://www.cms.gov/mcd/viewdecisionmemo.asp?id=238.

NICE in the UK is notorious for denying life-saving drugs to their citizens (one of the latest is Vidaza for myelodysplastic syndrome, which is a side-effect for CLL patients of FCR). This is one of the few drugs that is available for MDS, but because medical care is under the purview of the government, and not private insurance companies, there is real pressure to save money.

This is not a good development. Look for further degradation of the American health care system to 'save government money'.

Things pretty much the same

2010-08-15T23:32:00.000-07:00

No real changes to report. I have been a bit bothered by some pain in my duodenum. I found this out when I took a couple of aspirin because of some severe back pain I was having. I hurt my back when I filled my car up with gas. Perhaps a somatic response to the pain of paying $50 for a fill-up.

Anyway, besides the back pain, the pain in my duodenum, and miscellaneous pains elsewhere, more due perhaps to advancing age than the CLL, I have been feeling fairly well. I know that the average remission after flavopiridol (Alvocidib) is only nine months for 11q- folks like myself, so I'm half-way there. (My last treatment was in March.)

Unlike many chemotherapy regimes, most responders respond as well the second time to flavopiridol as they did the first time. I must be frank and tell you that I simply don't look forward to giving another eight months over to feeling fairly rotten two days of the week, four weeks in a row, with a blessed two week holiday after each cycle.

But if it keeps me alive, I would do it again.

And I understand that the treatment pattern has changed in the trial. Now, apparently, they are giving the drug for three weeks in a row, with two weeks off. Well, that's better than nothing!

My personal feeling (which may be totally without foundation) is that they might give flavopiridol once a month as a maintenance dose for those who do respond. The drug, it turns out, does depress the neutrophils, and perhaps the platelets, and the hemoglobin levels. So contrary to what I was given to understand, there is some hematologic effects.

In any case, I will see Dr. Kipps within the month, to see how I am doing. Since I stupidly did FCR, I am at a higher risk for MDS and Richter's transformation.

BTW, I did get a once-over by the dermatologist, and seem to be free from the other scourge of CLL patients, melanoma. I also have a fair number of dysplastic moles from my days as a frequent swimmer, hiker, and all-around pool guy. I love the out-of-doors, but there can be a price to be paid.

Counts holding somewhat steady

2010-07-22T06:59:00.000-07:00

A quick post: I've put myself on bi-weekly instead of weekly blood tests. The counts have improved to a certain extent, after the flavopiridol trial I was on last year/this year.

My hemoglobin count has improved to 12.0, after running in the 10s and 11s for the past two and one have years, after the poor decision to do FCR. My white count is now in the normal range, so no more neupogen or neulasta shots, for the time being. My platelets are also in the normal range, the first time in years (albeit low normal). I've been feeling pretty good, with no infections and no major problems.

So, as I've indicated before, flavopiridol (Alvocidib) is a great success for me.

It's not a cure, though. Everyone seems to relapse, and hardly anyone gets a complete remission out of it. My latest bone marrow biopsy shows CLL still present, and my spleen may have increased in size a bit. Nothing, though, that causes me any problems.

The average remission (which is in my case a partial remission) lasts 12 months for most CLL patients, and 9 months for those who have the 11q deletion, which is unfortunately my situation. However, one of the interesting things about Alvocidib is that is almost always works as well upon re-treatment. The treatment lasts eight months, and if I get nine months of remission, I could conceivably get eight plus nine months (17 months) for the first go-around, and another 17 months the second. This means I could perhaps get a total of THREE YEARS of decent health out of Alvocidib! For someone in my condition whose prognosis is regarded as 'grim', I think that qualifies as a miracle of sorts, thought Dr. T.H. probably wouldn't think so.

Anyway, I'm not cured, my CLL is still here, and my misguided use of FCR has made me much more vulnerable to MDS or Richter's, so I'm not out of the woods yet. However, at 12 months and counting after beginning Alvocidib, feeling good enough that CLL isn't pressing on my mind daily, is a great thing.

Would I do Alvocidib again? I'd say the pay-off is worth it.

Alan Sullivan

2010-07-19T07:14:00.000-07:00

I've linked to 'Fresh Bilge' at the right side of this page for some time now. I found Alan's blog by searching for other CLL blogs. I'm the type of person who deals with serious and threatening news by trying to gather as much information as I can.

Alan passed away from CLL on July 9, 2010, after an abdominal infection. He lived in South Florida and was cared for by Dr. D, as he called him. The focus of Alan's blog was not CLL; he was a life-long writer, translator, and poet. Fiercely bright and a talented writer, he translated Beowulf and other works. Of late, he was engaged in translating the Psalms into succinct but poetic form, trying to capture not only the sense but the lyricism of these great Biblical works.

He was a gay man, and politically conservative, so that made us alike on one count. He was probably more libertarian in his views (for some reason this is more acceptable to the left than conservatism is) than I am, and he was concerned about the direction of the country, given our seeming inability to deal rationally on the subject of government spending. I think he would agree with the sentiment that government and the taxpayers alike have to start saying 'NO!' to good and caring ideas.

He also was an amateur photographer, geologist, vulcanologist, and meteorologist. He lived in New England, New York, Minnesota, on his boat at sea, and finally on land in South Florida. The clever title of his blog refers to the water that collects at the bottom of most boats. Generally it's a foul mixture of water, diesel oil, and whatever else ends up the the lowest place on a boat. He said that he wanted his blog to be a fresh dose of whatever.

He said he was diagnosed with CLL in 2005. I don't know the course of his disease, or the treatments he pursued, but I do know that he was cursed apparently with an aggressive form of the disease. He chose to deal with the CLL by treating it palliatively; he underwent a round or two of irradiation to his troublesome abdominal nodes, a problem which I am all too familiar. Living with a cantaloupe-sized mass in your gut is annoying at best.

He started spiking fevers a few weeks ago, along with serious and debilitating abdominal pain. Since he posted every day (generally multiple times per day), all of this unfolded in real time. I was bothered by the fact that his fever would routinely top 102 degrees, before abating at some point in the day. Finally, he went to the hospital.

They found that apparently he had had a 'leak' from the bowel into the gut. His body seems to have sealed off the breach. He underwent surgery in early July to find out what was going on. He never left the hospital.

I never met Alan. I did post comments on his blog, and I did give him some unsolicited advice about his CLL. I mentioned clinical trials and flavopiridol. I also liked to tease him about global warming. He didn't believe in man-caused global warming, and he pounced on the news of the fabricated data from East Anglia University as proof that the only warming on the planet was in the fevered minds of the Al Gore crowd.

So, another voice stilled by CLL. So much for the 'good cancer' (an oxymoron if I've ever heard one). Alan was a bright guy with a whole host of opinions on science, politics, and life in general.

As he lay in the hospital, he asked that his blog be shut down, but that his writings serve as his epitaph. The blog is still available. If you are interested, he has a memoir section that speaks of his growing up in the fifties, sixties, seventies and beyond, in a country increasingly dysfunctional, and believing more in fairy-land economics and taxpayer expectations.

He is missed, and, like all of us, cannot be replaced or duplicated. I checked his blog every morning for a dose of wit, volcano postings, and musing on the weather. I'll miss doing that.

Retirement?

2010-07-02T14:11:00.000-07:00

I haven't retired yet! I found out that they change the retirement benefit upwards every quarter. The factor is related to your birthday, so as my birthday is in July, I will retire soon. (Because I have been so ill, I've been ready to retire on any day if my disease took a serious turn for the worse. So my wife says she will believe it when she sees that I've signed the paperwork.)

I have a number of reports to get done. Management is so anal-retentive (all woman management now, no men wanted), I have to go through every piece of paper and file it. So part of my day is now spent filing. We used to have secretaries do that, but we now need an analyst to file papers. Not smart nor efficient, but they don't ask me.

I will miss going to work. I like my job researching and writing, and I like most of my co-workers. We have a new set of managers (all women, of course) and they don't care if the work gets done, as long as you follow all the rules to the letter. No making up time (my old manager was great, which was nice since I ran out of sick leave a long time ago, and would have to use vacation time.

Baby boomers highly identify with their jobs. We find our place in the world based upon what we do. So I am not going to really retire. Not the kind of retirement where I'm lazing around the house, watching Judge Judy, bothering my wife. I've already signed up to take some classes, so I will be a part-time student. And I have my rentals to work on. I will just have more flexible management (me)!

To Port, or Not to Port

2010-07-02T13:43:00.000-07:00

I had my monthly IVIg this morning. I finally figured out that having it on my day off, I could save using vacation time (my sick leave, once around 1000 hours) has dwindled to zero).

They accessed my sad, diseased body via a Power Port, which is a type of subcutaneous port. Since it is entirely under the skin, one can shower, exercise, and do anything one would normally do without having to worry about protecting the area. What a relief!

The port was placed almost a year ago, in late July 2009. The only reason I had it put in was that it was a requirement of the flavopiridol (Alvocidib) trial I concluded in mid-March of this year. I suppose that was for convenience or to protect my veins.

At first it was pretty weird having a lump in my upper chest. It isn't visible with a shirt on (I wear baggy shirts because of my middle-age spread). It is noticable, of course, when I have my shirt off, but I never take my shirt off in public (people would complain about the unpleasantness). My new GP thought it was a huge boil, until I told him it was the port.

I couldn't wait to get the port out at first. It's a daily reminder of my serious illness. Now, after a year, I'm going to leave it there for as long as I conceivably need it.

It isn't perfect. I've bumped it a couple of time, working around 2x4s and the like, and one can't lean against anything in that area (like one would do reaching for something). I sometimes worry about it falling apart and causing a clot. (There is a noticeable tube that runs from the port into a large vein that empties into the heart; it's on the left side of my chest. That can be felt and would be catastrophic if it broke off and traveled to my heart.) And I think the worst risk would be if I was in a car accident and slammed into the steering wheel. Or even an airbag.

I bring it up because of my temporary neighbor in the infusion room this morning. He has a PICC line, which in his case is a series of three tubes that collectively go into a vein in his arm. He has developed an infection around the PICC line entry point, and once the nurses saw that, they became very concerned, paged the doctor, etc. etc. They suspect either a bacterial or a fungal infection. Luckily, it seems to be a surface infection and not into his blood (for now, at least).

I said a short prayer for my fellow cancer-sufferer. I hope he is OK. We are a brotherhood of sorts, I suppose.

An update

2010-06-26T08:34:00.000-07:00

I have been feeling OK, though my WBC is still very low, and my hemoglobin and platelets are below normal.

I suspect that there is something awry with my stem cells. They are not producing enough of most everything. This is called marrow failure, which is a term that describes what is obviously happening, but explains nothing beyond that. Little is known about marrow failure, except causes. Radiation is one big killer of blood-forming stem cells (hematopoietic stem cells), chemical poisons are another. A third cause is...chemotherapy! In other words, FCR.

It is possible this would have occurred on its own, since CLL allows more cancers to grow unabated. But since my counts crashed on the fourth cycle of that toxic regime, it's definitely linked to FCR.

Folks, please think about avoiding FCR if you can. Reserve it for when you have relapsed and are looking at a stem cell transplant. The combination of the 'F' and the 'C' (fludarabine and cyclophosphamide (cytoxan)) apparently are a potent producer of marrow failure, aplastic anemia and myelodysplastic syndrome (MDS). All of these are killers (six months to two years). Knowledge of these cancers is about where CLL was in 1995. It's terrible.

There are many other options out there. I made a serious mistake, being encouraged to try it by MD Anderson and seduced by the high complete remission data, etc. But everyone eventually fails FCR, and then the prognosis is 'grim'. Learn from my lesson.

Meanwhile, Dr. Kipps has been silent. I've been sending my blood numbers to them down in San Diego, but I've not heard anything. I am going to be prepared for an MDS diagnosis by making an appointment to see a doc at Stanford, where they have an MDS center, and a robust (as far as I know) stem cell transplant center.

Hangin' in there

2010-05-28T18:58:00.000-07:00

My blood counts in San Diego were truly worrisome. My white count, which had been recovering more or less from the end of treatment, dropped a bit a week before the SD trip. In San Diego, it took a huge drop, overall from 2.5 to 2.0 and then to 1.3. My absolute neutrophil count, though, was hovering over the magic 500 cut-off. I think it was something like 680.

I try not to take Neulasta or Neupogen unless I am in danger. After my first treatment with HDMP+R, my white count went down to 0.0. That's probably a false number, since I understand that in most labs, anything under 100 or so just leads to false readings. But I did end up spending four unpleasant days in the hospital, with a temperature maxing out around 105. Very dangerous territory.

A couple of years ago, after HDMP+R, but before ISF-35 and the hated FCR, my neutrophil count dropped to 103. The nurse apologized to me, saying he was sorry my count was low. I thought that was a bit weird, but maybe he thought I might not be around much longer. It's been two or three years, so luckily that never happened.

I was very worried that my counts would keep on dropping, so I had a CBC on Monday, five days after my last test. My white blood count bumped up to the usual low, but better, level of 2.5. My neutrophil percentage is at the normal (for me) level of 50%, so I'm OK, and don't need a $9,000 Neulasta shot.

I wonder how long that will be available for me? (Though the thing I really worry about is the IVIg, which is hellishly expensive, about $16,000 a month. My insurance pays for that, at least for now, but as time goes on, and government health care kicks in, this may go quicker than a dollar bill on a New York sidewalk (sorry, just made that up, though I'm probably not the first to use the saying)).

How do I feel? I was feeling fatigued and kind of low around the time of my SD trip, but now I seem to have rebounded a bit. I'm back to work full-time, and trying to salvage some folders (paper) that have mysteriously disappeared. What a pain to have to do over what you've already spent weeks to do previously!

I am going to retire this July, after 36+ years on the job. I can't really afford to, but my CLL is not going to let me go, apparently, so I just have to draw the line somewhere. I'll be 60 (the big 60...bummer!).

Unfortunately, like many CLL patients, I'm too sick to travel much, and the impaired immune system won't let me go to the places I'd REALLY like to go to, such as Mongolia and Vietnam and places such as that.

My advice to you? Travel now while you still can! (The crash has left me pretty broke, and that factors in as well.)

Memorial Day is upon us in the States; I'd like to have a picnic. Our tomatoes are coming along, and our peas are just taking off with the warm weather. Unfortunately, they won't be ready by Monday, but hopefully soon!

An update

2010-05-23T08:06:00.000-07:00

Two months after the cessation of hostilities (against my CLL cells and with collateral damage to my gut), I seem to be doing about the same, which is feeling pretty good. I am back to work full-time (although I really only took two days off a week while doing the treatment), and cleaning up loose ends. It is a task made more difficult with having supervisors who are much more focussed on their own situation, ensuring that work flow continues unabated by anything foolish such as illness. And by supervisors who cannot let work go out, but are intent on sending work back again and again until it is not only polished, but fairly sparkles. And that is for the most routine of tasks, such as letters to incarcerated folks looking for someone to talk to (men get this task, for we have had a number of cases where these men, who are so hungry for interaction with women, that they become letter-writing pests).

On the other hand, my CLL continues to inhabit my body. I did not expect a complete remission from flavopiridol (Alvocidib). Virtually no one gets one; I think only one person in the entire history of clinical trials using the agent has achieved even a complete remission, let alone a molecular one. So it's a partial remission I've received. And that's just fine. With a response rate of only 50%, it's fortunate that I responded at all.

One excellent feature of flavopiridol is that when relapse comes (an average of 12 months over-all, and 9.4 months for 11q del folks such as myself), the regime almost always works just as effectively the second time around.

This leads me to conclude that perhaps our two-faced friend might be used effectively as a maintenance drug. I like to think of one dose a month being enough to keep CLL at bay for a long period of time. But no one is testing that treatment regime, which I think is unfortunate. Really, really unfortunate.

And my partial response may not be a terribly solid one. My counts improved nicely over the last two months, and my hemoglobin and platelet counts are near-normal. For that, I thank God.

On the other hand, my white count, after improving each week, has now tanked for whatever reason. I've not needed a Neulasta shot for the two months, but I am now skirting along near the magic 500 number. If my neutrophils drop below 500, I will have to get a shot. Not good.

What could be causing this? The worst possibility is that the idiotic decision I made two years ago to take FCR has ruined my marrow, and given me myelodysplastic syndrome (MDS) a terrible new chromosomal insult resulting from the combination of fludarabine and cyclophosphamide.

MDS is becoming more and more common, as a result of chemotherapy such as FCR. MDS is where CLL was 15 years ago; few treatments available, and none of them effective at all. Survival estimates range from a few months to a few years.

Funny MD Anderson never warns you of the possibility of a fatal complication from using their beloved FCR. It may be unfair, but it seems that certain docs there love FCR, dole it out like candy, and just brush away concerns from patients like so much dirt under a rug. Gotta push the drugs!

MDS usually appears as anemia, and then progresses to take out all lines of the myeloid precursors, resulting in neutropenia (what I have) and thrombocytopenia, in addition to anemia.

I didn't get more than four months remission from the FCR. Definitely not worth the potential price.

There are other possibilities to be considered with neutropenia after FCR. One could be acute myeloid leukemia, a very nasty leukemia (especially in folks who acquire it secondarily to chemotherapy), or something called chronic myelomonocytic leukemia (CMML). Or perhaps aplastic anemia (AA). (The NIH says of the latter, "Secondary aplastic anemia may be an unavoidable consequence of treatments such as chemotherapy.) Nice. Only in CLL it is now not necessary to have chemotherapy.

Or it could just be a benign problem. Some people never recover neutrophils after FCR. Meaning that they stay on growth factors such as Neulasta for as long as they a-last-a (sorry). That is a remote possibility, but it is a possibility.

I had a bone marrow biopsy (my 15th, for those keeping track). Dr. Kipps is worried enough about MDS that he is running a special test looking for tell-tale signs of the disease. He wasn't particularly worried about it before, since it turns out that flavopiridol can lower neutrophil counts (which I didn't think happened).

So, as usual with CLL, I just have to wait for the results. I am praying for the best, hoping for the best, preparing for the worst.

What a penalty for making the mistake of using the FCR candy. Death. Not good. When will MD Anderson learn that there are much better options than that? Ever? They developed it, I guess, so they want to use it, over and over again. I guess it's the 'invented here' mindset.

What to do next

2010-04-24T13:10:00.000-07:00

For folks such as me, with the serious 11q deletion, eight months of flavopiridol (Alvocidib) gives, on average, a nine-to-ten month remission. That means, in total, start to finish, I'll have perhaps, on average, the need of something in 17 months, about a year and a half. (To be honest, that is pretty darn good realizing in how bad of shape I was in last July. My belly was rigid from tumor at the time.)

The question will be, what to do. The small study of flavopiridol patients show that five out of six patients who responded the first time, respond the second time, with a similar response rate, and a similar remission period. That means one might get 34 months out of flavopiridol! That's really, really good for people in my position.

Dr. Kipps has not mentioned doing flavopiridol again. And I really don't want to go through the CT scans again, just for the drug company's drug approval process. Perhaps I could ask for the drug on a compassionate basis.

He's also mentioned R&R (rituxan and revlimid) and ABT-263 as other options. Both of them have significant side effects; in the former, tumor flare syndrome, and in the latter, significant platelet destruction.

I would lean towards more flavopiridol, perhaps on the latest dosing regimen, which is three weeks on, and two weeks off. That would cut out one trip per cycle.

If I lived in San Diego, the flavopiridol would be more convenient and less costly, but I don't and it's not.

We'll have to see what Dr. Kipps says after the results of the scan and the bone marrow biopsy are in.

So how am I doing?

2010-04-24T12:49:00.000-07:00

I'm doing OK. I am a bit concerned because my numbers aren't up as high as I'd like them, but at least I'm off Neulasta for the moment (thank God!).

I feel OK but I've developed the weird hot flashes again, which I associate with CLL because I've had them before when my numbers were really high.

My WBC is still below normal, but have come up. My platelets are at 100, which is low but not dangerously low.

Flavopiridol has given me an additional nine months, for which I am grateful.

I just can't help wondering why, since everyone relapses from flavopiridol, they don't offer it as a maintenance drug, once or if a remission is achieved.

I had a CT scan (which I hate because the radiation is so high- you get a lifetime's worth of radiation during the trial if you do all of the scans the drug company wants). What do they care, though? It's not like it's their body.

I have a bone marrow biopsy scheduled for next month. That means another trip to much-disliked San Diego. And another $200 for the flight and taxis and the like.

I mentioned my taxes last post. I did get them done (on April 15th, natch). I do get a refund of the over-withholding because of large medical bills. Not only the sheer size of my deductible, but all the travel to SD. It's in the five figures, believe it or not.

In retrospect, I could handle everything easily, the vomiting (only one bout on an empty stomach), the abdominal pains that night, and the tiredness the next day or so. It's the diarrhea that is the big problem. It resolves, but it takes a few days, and it's unpredictable and very urgent. Meaning that you don't want to be more than a couple minutes from any bathroom, at any time. Lots of gas, too.

Not a good combination.

Sanofi-Aventis needs to work on solving that problem, or they won't find many takers for Alvocidib (flavopiridol). Except for desperate patients who have started running out of options, such as me.

Life and Taxes

2010-03-30T19:46:00.000-07:00

I am done with the flavopiridol/Alvocidib trial, and I have to get back to my life. I'm starting my federal taxes right now. In fact, posting here is a bit of a break from that very boring task.

I have long wondered why a few lucky souls who have deep, deep remissions of their CLL just drop out of the CLL society and 'move on'. It seems almost like a betrayal, doesn't it?

I will not be so lucky. My CLL has always been higher risk. When I was diagnosed, I exhibited the ZAP-70 marker, I was unmutated, and I had a 6q deletion, which is an intermediate risk marker. I was (and remain) male, and I was relatively young at diagnosis (48). All of those count as risk factors. So, from the start I knew I was not destined to be a smolderer. I envied all of those people (mostly female, it seemed) who could live with CLL and not have it be life-altering.

I delved deeply into the CLL on-line community, starting with the granddaddy (grandma?) of them all, the CLL list at acor.org, started by GrannyBarb. I learned a lot about CLL, and came to fear words such as 'refractory', and 'relapse'. I also learned that researchers are not one to pull punches; when I developed the 11q deletion, I read that folks such as me had a 'grim prognosis'. It's hard to let those words roll off one's back, isn't it?

Anyway, I am not going anywhere. At best, my flavopiridol trial gave me a partial remission. My terribly enlarged lymph nodes in my abdomen have shrunk, but not gone away. For 11q folks, published papers on flavopiridol show an average 9 month remission time. Then, apparently, the average person relapses. Based upon my previous history, my relapse may come sooner.

But at the present time, measured in weeks, I feel OK and feel as though I can devote a bit more time to work and family. Both have been pretty good, though one of my supervisors (she's since retired, thankfully) resented the fact that I was gone so much during my trial and demanded no let up in the work, which means that the three days a week I could work had to equate to five normal days. They did provide me with a converted small 'quiet' room that serves as my office. That was a great accommodation that allowed me to drag my room UV sterilizer in behind me and be somewhat isolated from the germs around the office.

In any case, I will be retiring this May. I really, really enjoy my job, but with that 'grim' prognosis hanging over my head, I can't justify working any longer. My retirement benefits to my wife would go way down if I die will still employed.

I used to have a co-worker who was diagnosed with colorectal cancer when he was in his early 50s, I think about 52. Kaiser did surgery, and he did well for a couple of years, and then the cancer came back. He retired when he started having lung mets. The doctor told him he had about three months left to live. It turned out he was gone in three weeks.

I want to have a retirement that lasts longer than my poor co-worker. So, it's adieu for all of my friends at work, and good riddance to the rest of them!

I hope I have more than three weeks.

Finished with Flavopiridol

2010-03-26T09:33:00.000-07:00

Last Wednesday March 17th, I finished with the 24th and last treatment with flavopiridol. My side effects were the usual, nausea, one bout of vomiting, and diarrhea. I've found that if I just get the vomiting over with, I'm done and the nausea is improved. The diarrhea lasts a couple of days. Inconvenient, to say the least, especially since I have an hour and 15 minute flight back from San Diego.

I fast the day of the treatment, and eat nothing the next morning as well. I find that the vomiting is better without anything in my stomach. The vomiting is the least of the side effects, since it is over in one session. Once I throw up, it's over. I can certainly tolerate that.

The other side effect is general malaise that evening. I go to the hotel immediately after the treatment, and I go straight to bed. I have to get up and go to the bathroom several times, of course. The other problem is for about an hour and a half, I have noticeable abdominal pain that lasts about an hour and a half. I sleep on and off the rest of the night. I am wiped out the next day, and I usually go to bed early Thursday evening and sleep for 10 hours.

Is it worth all of the discomfort and the expense (I've spent about $8,500 in transportation costs to UCSD, none of which is reimbursed). I think so. I've had a partial remission, which is remarkable in a case such as mine. Without flavopiridol, I would be in big trouble by now, perhaps even gone. I suppose there are other treatments to try, but once you've failed FCR, you are in big trouble.

And, of course, everyone fails FCR, eventually. (So why do it? That is a good question, and I wish to heck I had never done FCR.)

Research has shown (in small samples, which is what clinical trials use) that about 1/2 of refractory CLL patients (such as myself) will respond in some way to flavopiridol. Responses range from nine months to just over one year. People who fall out of remission can be retreated with flavopiridol again, and most respond again with the same level of response, which is remarkable.

Would I do it again if and when I fall out of my partial remission? Yes, I suppose so. The treatment is not pleasant; but there are very few options at this point in my life, and the time away from treatment is usually pretty good. During the treatment, Wednesday (the day of treatment) and Thursday are usually just gone, I can't do anything. By Friday evening I'm feeling better; by Saturday I'm usually feeling pretty good. So I have five days a week of feeling pretty good, and two days a week of not feeling very good. But, my options are few at this point.

I thank God that there is this option for me.

I go next month for the CT scan to see how my nodes have responded. I expect to see some improvement, but no total resolution of my nodes, and certainly no cure, or even a complete response.

But, beggars can't be choosers.

Last few days of freedom

2010-03-19T19:42:00.000-07:00

I generally refrain from making political comments on this blog, since I'm not a terribly partisan guy. I cut my political teeth working for Democratic candidates for statewide office. I had a lot of fun and every campaign I've worked on has ended victorious. I've voted for several political parties.

But this health care bill will be a disaster for the United States. It's not so much this bill, though it raises taxes and 'front ends' those tax receipts for years before they are spent giving health care for millions of people who don't want to pay for health insurance until they need it. It will soon run a deficit.

The socialist left just wants a foot in the door. Once they get their vast bureaucratic agency, they will just add, add, and add to the socialized medicine system. Eventually, it will be government-run health care, a single-payer system.

You want to see how that works? Look at the UK health care system. Health care becomes part of the federal budget, competing with defense, education, social security, highway funding and everything else. There won't be enough money to keep care at the present level of excellence.

In the UK, there is an agency that was created to cut funding for cancer and other drugs. It's called NICE, and it's anything but. NICE has refused to fund scores of cancer drugs, because they are 'too expensive'. These drugs (which up until now have included Rituxan)are saving lives in the US. They are not saving lives in the UK, because the government can't afford to pay for them.

Don't believe me? Search on 'NICE denies cancer drugs'. Now, that doesn't affect me, because up until now, the US has a private health insurance system that spreads risk around, and doesn't have to pay for a vast bureaucracy that will be so inefficient it will make the DMV look like a paragon of efficiency.

But what do I care? I have a fatal disease, and I am likely to die before the socialists totally destroy health care.

I suppose it's because I care about my fellow cancer patients. I have relatives who will suffer once the federal government swallows health care. They will not have the same excellent coverage as I do now.

I suspect the first thing to go for CLL patients is IvIG, intravenous immunoglobulin injections. They are valuable to CLL patients with there terrible immune systems, but they are expensive and have not been shown to prolong survival. It's a quality of life issue, but don't count on it being there in a few years.

One funny thing? The pharmaceutical companies, who got Obama to promise to not negotiate lower prices for drugs, in exchange for their support. What are they going to do when they won't be able to sell their ridiculously expensive drugs at all?

Serves them right.

Combine this with the government seizure of GM, Chrysler, the student loan program, providing internet access to all Americans (at taxpayer expense, of course), and you have a road map to socialist nirvana. Everyone will be beggars at the government teat. And, once the government says no, you have no place to go.

I will leave you with a quote, and see if you know it:

"Still one thing more, fellow-citizens—a wise and frugal Government, which shall restrain men from injuring one another, shall leave them otherwise free to regulate their own pursuits of industry and improvement, and shall not take from the mouth of labor the bread it has earned. This is the sum of good government, and this is necessary to close the circle of our felicities."

It was the good and wise third president of the United States. He mentioned a 'frugal government' twice.

Boy, that isn't the case now, is it?

Penultimate Flavopiridol Treatment

2010-03-12T16:17:00.000-08:00

It was my next-to-last flavopiridol (Alvocidib) treatment last Wednesday. I did probably the best I've done to date with the side effects.

I've been having nausea with every treatment starting mid-way through the eight-month treatment. This time was a little different. I started to feel queasy toward the end of the treatment. I was very late in getting the bags of the chemo; they were busy at UCSD and short-handed. So it was late in finishing up. My nurse Dan (who is great) took over when he got there (I think it was his late day or something; he did stay late).

But about an hour before I was released I started thinking I was going to throw up. Nothing happened. But I've noticed I've gotten some phlegm that starts going during the treatment. Anyway, I did finish the treatment without throwing up. Usually I make it to the motel before I throw up (if I do; it's about 50-50 that I do).

This time, I was 'unplugged' and going out the door when the nausea hit. I made it to the restroom at the Moores cancer center, but then I threw up. It's only one episode of multiple heaves (sorry for the grossness). Once I've thrown up, it's over for good. So I can't complain too much. And, to be honest, if I try to maintain, I just am nauseated for a longer period of time. So, just be done with it!

Once I got to the hotel, I was OK. I did have the diarrhea, but it wasn't too bad this time for some reason.

Fasting: I do fast the day of treatment. There is no reason to eat something, just to have it come up later. I also don't eat anything Thursday morning or afternoon. Believe me, I don't want to eat, so it's easy to fast.

Results look OK but I'm still dealing with low neutrophils, as a direct result of FCR. I wish I'd never done FCR.

Were do they all go?

2010-02-25T19:21:00.001-08:00

I was discussing some mutual CLL friends with the spouse of a (sadly) deceased CLLer. We both agreed that we had lost touch with a number of outgoing, well-regarded CLL patients. Where do they go? Have they died? Have they just moved on, and stopped posting on the various CLL lists?

I could, but won't, name names. I do know that on many occasions, we get the sad news from a spouse, son or daughter, that their loved one has passed away from this crappy disease. I remember one case that bothered me a lot. The daughter of a proud, older farmer who had developed CLL had written in asking for advice. I gave links to websites, put in my two cents on various subjects, and tried to help anyway I could. Unfortunately, her father passed away from CLL after only a couple of years.

But what about people who just disappear? I know in one case a woman who went through HDMP+R (high dose steroids plus rituxan), and followed it with Campath, had such a good response she just stopped posting. She let her website lapse. I feared the worst. But, she finally answered my e-mail. She said she was just putting CLL behind her. (What a wonderful outcome for her!)

Others just disappear without a trace, and I'm reluctant to e-mail them or search the obituaries. No news is good news, sort of thing. I suspect that most of the friends I've had with CLL (some of whom I've met in person) have passed away.

Really, I wish they'd have a loved one let us know what has happened. I know it might be difficult to let the rest of the world in on your grief. I've left instructions to my wife to write to various lists if and when I pass away. (It doesn't have to be from CLL, now does it? Car crashes kill over 40,000 people a year in the US.

One CLL memorial page is at: http://www.cllfoundation.org/Memorial.aspx. At least this page lets us know what happened to some of our CLL friends.

Am I going to watch the Super Bowl?

2010-02-05T19:30:00.000-08:00

The occasional reader who drops in when searching blogs on the NFL or Michael Vick may remember that I am boycotting the NFL since that 'august' body signed Vick to a huge contract after he cold-bloodily murdered his own dogs.

One respondent to my post sharing the fact that I am not going to watch the NFL as long as they allow this monster to continue in gainful employment said that the loser Vick 'made a mistake'. Yeah, like, 'I was going to the store but I killed my dogs instead'? That kind of a mistake?

But, now, the Super Bowl (and all of the hype) is coming up. The evil Philadelphia Eagles and their degenerate former quarterback Vick aren't in it, so maybe I can break my vow and at least watch the commercials?

Naw. As compelling as the game might be, I just can't lend my eyeballs to the venal NFL, who obviously cares more about money than justice for animals.

Mr. Vick is reported to have electrocuted, strangled, and stomped his own dogs to death when they disappointed him.

He does not deserve anything good to happen to him for the rest of his sad and pathetic life. I hope he gets what he deserves in this world, or the next.

Neutropenia

2010-02-01T19:17:00.000-08:00

Since my unfortunate decision to undergo FCR (fludarabine, cyclophosphamide and rituximab), my neutrophil count has hit rock bottom, and pretty much stayed there. In fact, the low white blood count was the reason I only did four of the normal six cycles.

The neutropenia improved since January 2009, which coincided with the end of the four-cycle treatment. In the spring of 2009, I was on neupogen or neulasta for several months, with the low point being reached when my absolute neutrophil count plummeted to 106, well below the dangerous level of 500.

I did not need neutrophil support in the late spring, summer, and fall of 2009. However, beginning in late November, my neutrophils have dropped to dangerous levels again.

My counts are buoyed by the colony support factors neupogen/neulasta, with each course lasting 2-4 weeks. However, it may be that I am now neupogen/neulasta dependent, which is dangerous. Dangerous because artificially stimulating the production of neutrophils can lead to myelodysplastic dysplastic syndrome (MDS) or even the aggressive leukemia acute myelogenous leukemia (AML).

I'm hoping and praying that this does not happen.

Other than boosting my level of exercise, I know of no way to increase the production of the stem cells that were damaged by FCR.

That is one reason I have soured on the idea of using FCR. A well-known (though I had not heard of it prior to researching marrow failure) side effect of fludarabine in combination is secondary MDS, more difficult to treat than de novo MDS.

Live and learn. Though the learning might be easier than the living, if things go against me.

Even without MDS, I am perpetually at higher risk for infection being frequently neutropenic.

Not a happy place to be in.

OTOH, the flavopiridol/Alvocidib is still apparently working, though the side effects associated with the drug has not. I am scheduled for the last treatment in this fifth cycle on Wednesday, February 3.

Syncope after Alvocidib

2010-01-30T14:49:00.000-08:00

Yes, I had a nice side effect from my treatment in late December.

Since I live in Sacramento and fly to San Diego each week to do this trial, I stay in a motel that night. I usually feel so terrible that I just don't want to move. I guess I could fly even in misery, but the Alvocidib (flavopiridol) gives me frequent watery diarrhea (joy, joy, joy!) so I just don't want to be buckled into by seat at 35,000 feet with a very urgent need to use the bathroom, only for the stewardess to tell me the fasten-seat belt is on, and I have to return to my seat...

So I checked into my motel on late December evening, feeling rotten as usual. By rotten, I mean nauseated and with abdominal pain. This time, in order to cut the amount of potassium in me, without using the horrible Kayexalate (just thinking this word makes me want to throw up; such is the power of the mind), they gave me a Lasix pill.

So, I'm checking in, trying just to get the key card for the room, when (apparently) I fainted and ended up passed out on the floor for a minute or two. I remember the desk clerk asking, 'should I call 9-1-1?' Of course, they did. So I had yet ANOTHER night in Hotel 'd Thornton (hospital). Joy, joy, joy!

When I fainted, I apparently hit my head on the rather hard tile floor in the lobby. The back of the head hurt. I asked the junior doctor at Thornton (who looked about 15) if this was a danger for someone with low platelets (yes, my platelets got into the normal range and promptly fell again). He said, no, the platelet level of nearly 100 would not cause any abnormal bleeding. So any lapses in memory or cognition would just probably be overlaid in my aging brain and not be distinguishable with the other insults that have happened over the years (and there have been some, due to sports).

So, you get Lasix with your flavopiridol, ask for a crash helmet to protect you if you end up passed out on the floor.

Last Minute Donations to CLL Charities

2009-12-31T09:02:00.000-08:00

Nothing like waiting to the last minute!

If you want to make some 2009 donations to further the cause of CLL research, please consider the following organizations:

Perhaps you remember the research effort into finding the antibody which may wipe out all CLL cells? That effort excited Dr. Byrd at Ohio State and a CLL guru. The sooner we get this in trials, the better. The address for donations is:

The National Cancer Institute Gift Fund, Building 31/Room 11A-16, 9000 Rockville Pike, Bethesda , MD 20892 . The check should be made out to the National Cancer Institute and the cover letter should request that the donation be used to support translational CLL research such as that conducted by my laboratory.

The other organizations that help support CLL research include Dr. Kipps' Blood Research Fund:

https://www-er.ucsd.edu/givetoucsd/secure/paymenttran/onlinegiving.asp?sk=42

Dr. Keating's CLL research fund is at:

http://www.cllglobal.org/donate.htm

The Kanzius machine that may help treat CLL is being tested at MD Anderson. It uses nanoparticles to attach to CLL cells; heat is then applied body-wide to destroy the cells.

http://www.kanziuscancerresearch.com/supportthiscause-p-163.html

PLEASE PLEASE PLEASE donate to destroy CLL. We need a cure NOW!

And, please all of you one or two people reading this, have a safe and healthy New Years Eve and the same for all of 2010. May this be the year CLL is cured.

A belated "Merry Christmas"

2009-12-26T11:45:00.000-08:00

I was too sick yesterday to get on the 'net and post here, but a belated Merry Christmas to all!

I am having continuing problems with my gut, bloating, gas, etc. etc. I don't know whether I have an infection or this is the result of the Alvocidib (flavopiridol). I am going to the urgent care clinic to find out this morning. It is troubling and very painful.

Be well, all.

The Most Common Leukemia?

2009-12-18T15:50:00.000-08:00

For many years, CLL has ‘reigned’ with the title of ‘most common leukemia in the Western world.’ That title may be in jeapordy, though, if recent trends continue. Already some say that the title has already fallen to another contender. What is this mystery leukemia that seemingly has come out of nowhere to grab the crown? Myelodysplastic syndrome, or MDS.

Perusing the ASH abstracts, a number of papers caught my eye, including this one: http://ash.confex.com/ash/2009/webprogram/Paper19496.html. The authors say that “Myelodysplastic syndromes (MDS) are becoming the most commonly diagnosed forms of leukemia in the US .” Also, consider this very interesting paper that asserts that MDS may be afflicting over a hundred thousand Americans: http://www.moffitt.org/CCJRoot/v16s4/pdf/2.pdf

One reason MDS might be increasing in frequency is that it can arise as a result of chemotherapy for other cancers, including fludarabine-containing regimes such as FCR for CLL. As cancer patients live longer (always a good thing, of course) other cancers will make their presence known, unfortunately.

San Diego Water Is Bad- Here's Confirmation

2009-12-12T15:50:00.000-08:00

I have gone to San Diego many times for treatment. I try to keep hydrated to help flush toxic materials produced from the treatment.

It's difficult in San Diego, because the water is the worst-tasting water I can remember ever trying to drink. Bleech!

I have been thinking about taking some flavored powder to add to the water. I know the importance of staying hydrated, and any help killing the taste would be welcomed.

This is from Yahoo.com
(http://green.yahoo.com/blog/the_conscious_consumer/110/cities-with-best-and-worst-tap-water.html)

Cities with best and worst tap water

By Lori Bongiorno
Posted Sat Dec 12, 2009 10:55am PST

More from The Conscious Consumer blog

How safe is the water that flows out of your tap? The answer very much depends on where you live.

It's now easier than ever for consumers to find out what's in their tap water. The Environmental Working Group (EWG) today released the results of a three-year investigation of municipal water supplies across the U.S.

The research and advocacy group looked at water quality tests performed by water utilities since 2004 and created an extensive database that contains info on the contaminants found in 48,000 communities in 45 states.

EWG also rated 100 big city (population over 250,000) water utilities. Below are the top and bottom results.

Cities with the worst water:

1. Pensacola, FL
2. Riverside, CA
3. Las Vegas, NV
4. Riverside County, CA
5. Reno, NV
6. Houston, TX
7. Omaha, NE
8. North Las Vegas, NV
9. San Diego, CA
10. Jacksonville, FL

The article suggests the water isn't particularly safe. I don't know about that, but I can tell you the water just tastes terrible.

Platelet Numbers Increasing

2009-12-05T11:04:00.000-08:00

I've had CLL since October, 1998. I 'celebrated' my anniversary this last October by doing nothing, since being diagnosed with a terrible, incurable disease which will likely take my life is nothing to celebrate. Curse, maybe, but not celebrate.

As my rare reader probably knows, I started on a phase II clinical trial of Alvocidib (flavopiridol) in late July. I'm a bit more than half-way through the trial, which, if I make it that far, will last nine months and end in the latter part of March, 2010. (An aside: I wonder if this change in the year will FINALLY cause people to stop saying the year in the most ridiculous manner possible, i.e. two thousand and nine instead of the proper, twenty-oh-nine. Correct me if I'm wrong, but did we say, for example, 1998 as one thousand, nine hundred and ninety eight? I don't think so...)

I get a weekly blood draw; when I'm in San Diego, it's through my port, when on my infrequent trial holidays, it's through the veins in my arm here in Sacramento. I noted a trend about a month ago that my platelets were up a bit. I've been running below normal in my platelets since about 2003. Nothing major, but they've oscillated up and down between 55 and 95, usually hanging out around 70-80. My count on October 9, 2009, for example, was 82. This is not a dangerous place to be, but I don't go skydiving or race cars as I don't what a subdural bleed. No siree!

The last three blood tests in November, the last two done here in Sacramento, show the improvement continues. My 11-12 test shows my platelets were at 95. On 11-18, they topped 100 for the first time in many years at 101. My November 25 blood draw had the platelet numbers at 134, the first time it has been in the normal range, as I've said, in many years.

I can only guess this is the doing of the flavopiridol. None of the other treatments that I can recall worked so well on platelets.

Obviously, I'm pleased.

And while this happy situation won't last forever, and my number will likely slink back to the less happy situation of low platelets and increasing tumor burden, today, I will make the most of it. I was thinking that I don't have to have any real worries about shaving, getting cut, having nosebleeds, bleeding profusely at the slightest nick, and so on. I might even take a fish oil tablet for the heck of it, since heart disease runs in the family, and I now have enough platelets to clog an artery or two.

The other numbers are still in the abnormal range, though the hemoglobin has been above 10.0 for over quite a while, at least out of the danger range for well over a year (I've had to have blood transfusions on a number of occasions - thank you blood donors!!!).

So the platelet counts are fab, and I'm thankful for that. I still have CLL cells everywhere, but they have been beaten back for the time being. And in spite of those bureaucrats, especially in socialized medicine England, who say six months of extra life if just no big deal, I will tell you that my decent health since I've started flavopiridol is priceless to me.

Two Weeks Off!

2009-12-04T10:15:00.000-08:00

The clinical trial protocol of flavopiridol (Alvocidib) is a long one, with the full course lasting nine months. (I started in late July and if all goes well, I'll have my last infusion the end of March, 2010.) It consists of six cycles of four weekly infusions, followed by a two week 'holiday'. It has been suggested that the infusions should just run continuously so that the drug can work continously to kill CLL cells, but the trial protocol is set up with the two-week break.

Being the patient, I can say that I will not protest too much that I get a two-week break. Part of the procedure using flavopiridol is that one cannot have too high of a potassium level. I've discussed this before, but the dying CLL cells dump the cell contents in the blood, and this can cause acute renal failure which has been fatal in at least one patient in the phase I component of the study. Starting off with a low normal level of potassium (3.9 or thereabouts) means that there is room to go up without doing anything drastic in terms of managing the potassium level.

So, I try to manage this by drinking lots of water spaced throughout the three days before going down to San Diego for the next infusion. (There is a danger of drinking too much all at one time. Search on 'water intoxication.') I also go on a low potassium diet, which I have devised. This is basically a 'white' diet consisting of white bread, white cake, white cookies, muffins, etc. Few vegetables and no meats are low in potassium. Also, no chocolate. The 'diet' is more comprehensive, of course. And, of course, don't do anything without checking with your doctor as I have.

This means that my diet is severely restricted for the Sunday, Monday and Tuesday before the Wednesday infusion. (I fast on the day of the infusion because anything I eat will just come up later. And I will have an aversion to that food for a long time. As it is now, the thought of raspberry juice is revolting, since I used to buy a raspberry Snapple and wash down pills with that. Bleech! Sorry, Snapple.)

So...I can have a normal diet for Friday and Saturday. Only two days a week. Of course, things could be a lot worse.

Anyway...I had a wonderful two-week break the last two weeks of November. This included Thanksgiving. My wife is a great cook and we had a turkey breast (thank you mister or miss turkey for giving up your life for my meal) with the usual fixings. I had Thanksgiving and the day after off from work, so my wife and I spent one day up in the foothills of the Sierra poking around various antique shops.

We try to do two trips a year in Amador City and Sutter Creek. These two are delightful towns that are only 30 miles from Sacramento, but with a totally different feeling. It's a beautiful drive up highway 16 east of Sacramento, then south on highway 49. It's especially pretty in the fall with the changing leaves on the trees, the cold air, the wood smoke in the air, and the happy tourists clogging the streets.

We spent the day looking at and for various fun things to look at or to buy. Sutter Creek has a crafts fair most weekends from Thanksgiving to Christmas. Both towns have some unique shops that carry things you don't ordinarily find. My wife's favorite shop is in Amador City, and features antique lace. Now, as a guy, I don't know why anyone would want to wear 100-year-old fabric, but my wife puts together some attractive looks mixing old lace and modern clothes.

It may not be the best way to administer the flavopiridol, but having a two-week break from the tedium of flying to and from San Diego, and spending the day in the infusion room isn't all bad from my point of view!

I'm more than halfway through the regime. So far, it has been working pretty well.

Life without the NFL

2009-11-21T11:19:00.000-08:00

As the passing reader may remember, I am boycotting the NFL because they rewarded the evil dog-killer Michael Vick with millions of dollars. Business and stupid fan loyalty has allowed this to happen.

Well, I won't have any part of it.

I have avoided any television and radio broadcast of the NFL this year. Withdrawal, as you might imagine, isn't difficult, especially with the panoply of college games on the boob tube. I enjoy football, I enjoy watching the plays and the strategy unfold, and I find the college game to be more rewarding than the pro version.

For many decades, college football was the only game in town. The pro league was an afterthought watched by dozens of fans every year. I don't know why it changed; I suppose a case of severe laziness on the part of Americans. Not only can they watch college football on Saturday, but they can (if they support dog-killers) watch the pro version on Sunday, Sunday night and Monday night.

I have to confess I enjoyed watching the pro version if my team, the San Francisco 49ers, were playing. The 1980s teams with Joe Montana were almost all-consuming on Sundays. If I were going to be out of town (I used to hike on Sundays frequently), I'd tape the game, every last game.

I must say I don't miss the pro version at all. The 'crutch' of college football has helped ease my withdrawal, and, to be fair about it, the pro version only lasts five or six months of the year anyway. So I've had to suffer the withdrawal every year for six months, anyway.

And there is always baseball. Baseball is the best game to listen to on the radio. You don't have to watch the plays, since there is only one or two players involved in most plays (unlike football where there are 22 players on the field, most of the time). And baseball lasts seven months, plus there are the exhibition games when it's also fun to listen to. Baseball is kind of boring to watch on television; radio or live is the best.

All in all, let the NFL celebrate dog torturers and play with their over-paid players, over-paid coaching staff, and maniacal owners fiddle around with their delusions of grandeur. I'm not part of it, anymore.

Might a Major Development in CLL Treatment Be in Sight?

2009-11-20T11:58:00.000-08:00

I was perusing the Web looking for interesting CLL news, when I decided to look at Dr. Kipps’ Blood Cancer Research Fund site (www.bcrf.org). The site now posts news from “Blood”, the periodical of the American Society of Hematology (www.hematology.org).

I noted an interesting editorial from Dr. Byrd on the discovery by researchers of the National Institutes of Health of a single antigen on CLL cells that may be common to all CLL cells. (An antigen is a protein that is the target of an antibody.) Dr. Byrd practically gushes with enthusiasm for the possibilities for CLL and other blood cancers from this discovery (http://bloodjournal.hematologylibrary.org/cgi/content/full/114/20/4324). In fact, his editorial is entitled, “Hunting for the Achilles’ Heel of CLL”. He terms the value of the process in identifying the antigen common to CLL cells as ‘immense’.

That sound like extremely good news!

What the researchers did was to look at people who were cured of their CLL by allogenic stem cell transplants (SCT). They then compared the blood to the patient’s blood and CLL cells that were preserved from the time before they had their transplants. (Research such as this is the reason donating blood for research is so important.)

Using sophisticated techniques, they were able to identify an antibody to an antigen that was present on the CLL cells in these patients before their transplants. The antibody wasn’t present in the patients (otherwise they presumably would have never developed CLL in the first place), but was produced from the donor’s stem cell derived B lymphocytes. It appears that, once the donor’s stem cells start producing those lymphocytes in the transplant patient, somatic hypermutation (which is the process where by all antibodies are produced by the body), starts working to produce an antibody which then starts to destroy CLL cells.

Byrd envisions development of this work to leading to therapies that may improve the curative potential of stem cell transplants. He also suggests that this may find a place in non-transplant therapies in treating CLL and other blood cancers. Avoiding the very expensive, very complex, very disruptive, and dangerous STC would be highly desirable!

Flavopiridol-Three Month Mark

2009-11-14T11:20:00.000-08:00

On Thursday, November 12, 2009, I completed the third cycle of a planned six-cycle phase II clinical trial of Alvocidib (flavopiridol). Each cycle consists of four weeks of a one-day per week dosing, followed by a two-week 'holiday'.

As I've mentioned before, there is some thinking that as long as the drug is working, why stop it for two weeks every month? I concur with that thinking, especially if a continued pounding of CLL would conceivably result in a cure. However, flavopiridol has, per the latest published results of the trials (http://tinyurl.com/yhhp286) using the drug, only resulted in one complete remission. The over-all response rate was 53%, most of which were partial remissions. There was one complete remission in this study, which I've not read has occurred in previous studies.

And I must admit the two-week holiday is something to look forward to. It would be different if I lived in San Diego, but I don't.

My own experience is that I have responded to the drug. My main complaint prior to enrollment in the trial was large abdominal lymph nodes. I was doing my best to treat the lymph nodes with 3 mg per day of EGCG (the green tea component) and what ever else I could think of (curcumin, PEITC through watercress, vitamin D3, exercise, etc.) Eventually the lymph nodes elsewhere in my body, which had remained very quiescent, started growing.

My blood numbers have remained quite low since my sad experience with FCR, so low, in fact, that I worry I may never recover what passes for normal bone marrow function in a CLL patient.

My lymph nodes (especially abdominal) have been my greatest complaint.

After three cycles of flavopiridol, what have I learned? This is not a terribly easy drug to take, although I have learned how to mitigate many of the side effects. The first problem is the terribly ill feeling I get the evening after getting the drug. I feel very sick, very nauseated, often vomit, have persistent diarrhea, and just plain feel terrible. I have an elevated heart rate as well. It is all I can do just to get into bed and ride it out. Several times I have felt so unwell that I had to go to the emergency room.

To counter the nausea, I've insisted and insisted on adequate anti-nausea medication, which is surprisingly difficult to get. I guess everything that is given on a clinical trial has to be per the protocol, or you don't get it (exceptions of course are made; people don't die because life-savings drugs aren't on the protocol). I take ativan prior to the start of the flavopiridol, and get injectable zofran. This helps; I also have ativan and zofran to take if I feel nauseated later in the day.

The diarrhea is a problem, since I fly from San Diego back to Sacramento the day after getting the drug. After some experimentation, I use Immodium at the first sign of problems, and I take yogurt for the probiotics after I get back home. This (so far) had made the problem more mild.

The fatigue is something all CLL patients are used to; you just rest and do what you can do. It only lasts for the rest of the second day. By the third day, I'm back to the generally low-level of energy which accompanies CLL.

As I mentioned in the last post, I avoid the diarrhea-inducing medicine at all costs. Just thinking of it, or seeing the bottle, or remembering the taste makes me ill and wanting to vomit. Bleech! So I go on a low-potassium diet for three days before the treatment; this has kept my potassium level below the magic 4.0 so far. However, this is a very restrictive diet; I have created a chart of a variety of foods with their potassium levels. This means no fruits, nochocolate, no potatoes, no tomatoes, no soy, no milk, no bananas, no meats of any kind, no carrots, no raisins, no yogurt, no bran, no multi-grain breads, no nuts, no orange juice, no beans, and so on.

You are allowed white bread, white cakes, white cookies, rice krispy bars, water, oils of any kind, and small portions of cheese, iceberg lettuce, olives, pasta, and most soft drinks. But it is worth it to avoid the diarrhea-producing drug!

So, at this point, both Dr. Kipps and I are satisfied with the results. Flavopiridol can work on heavily-pretreated patients with unfavorable prognostic indicators, such as me. Thank God (and the researchers and the pharmaceutical industry)!. Otherwise, who knows where I'd be right now...

Flavopiridol

2009-10-11T12:01:00.000-07:00

After much thought and a thorough examination of the options available to me, I decided to go with a flavopiridol trial at UC San Diego. I've been treated at UCSD before, I really like Drs. Kipps and Castro, and I can fly down there and back in a day if I can manage it.

Flavopiridol, also known as Alvocidib, is a cyclin-dependent kinase inhibitor. It has been suggested that it helps promote CLL cell apoptosis, or programmed cell death; it also slows the growth of cancerous tumors.

The drug has an interesting past. It was discovered to have a very profound CLL cell killing effect in the test tube, but when tested in humans, it seems to have no effect at all. The drug was set aside, but 'rediscovered' and looked at again. It seemed hard to believe it could blast CLL cells in the laboratory, yet do nothing in patients. Finally, they figured out that the drug would bind to human serum proteins, leaving precious little available to kill the cancer cells.

After much more experimentation, a different dosing schedule was worked out. The drug is now given in two stages, one dose to bind to the blood proteins, and another to go in an hour or so later, in hopes it will kill CLL cells.

I started on the trial in late July. The clinical trial calls for the drug to be given once a week for four weeks, then a two week 'holiday'. Theoretically, this regime could be given for up to nine months, as long as the disease doesn't progress or the side effects aren't too terrible.

(Dr. Kipps told me he doesn't understand the need for the holiday, since the drug is not myelosuppressive (i.e. it doesn't cause damage to the bone marrow or lead to depressed blood numbers)).

The first two times are down with a hospital stay. This is precautionary since there have been deaths associated with the drug. The cause of death is massive cell death, or tumor lysis syndrome. The massive cell death can dump cellular products into the blood that overwhelm the kidneys, leading to acute renal failure. It is my understanding that the first patient treated with flavopiridol died from renal failure.

The stay in the hospital allows for a quick hook-up to a dialysis machine if tumor lysis syndrome occurs. This did not happen to me. Instead, they managed the blood numbers (they primarily focus on the potassium level) by inducing diarrhea. I can attest that the drug they use to induce diarrhea works very well. I was up and down on the pot about 35 times the first stay in the hospital (my poor roommate was pretty much locked out of the bathroom).

After the first two weeks, the patient is treated in the infusion room.

So far, I've had two stints of four infusions each. The treatment has worked well; my blood numbers haven't changed much, so there is no impact there (although my blood numbers have been very low since my disastrous acquaintance with FCR). The main benefit has been in my spleen and abdominal nodes. I've had shrinkage in the massive nodes in my abdomen and in my spleen.

The main adverse side effect has been my development of a severe aversion to the diarrhea-inducing medicine. I cannot tolerate the taste, the smell, the sight or the thought of this drug, (Kayexalate). I started to get sick after taking this about the fifth time, and I ended up in the hospital vomiting for an hour or so.

What I do now (and I REALLY wish I had know this going in) is to go on a low-potassium diet on Sunday before my Wednesday infusion. If you have a level below 4.0, they won't force this vile stuff on you. So I am VERY, VERY careful to have a low potassium level before I do the flavopiridol.

It is such a negative effect that I probably would drop out of the trial.

The other thing that they didn't do is routinely treat me with anti-nausea drugs before the treatment is started. Instead, they wait until I start vomiting. Dumb! Anyway, I now take my atavin and zofran with me and take it before I start on the treatment. The last time I was down there I only vomited a couple of times.

The other really odd side effect is what happens about four hours after the treatment. I suddenly feel terribly ill, ready to go to the emergency room with a fever and general malaise. However, it passes after a half hour or and hour. However, I am ready to call 911 if I have to.

So, flavopiridol seems effective, but is not the easiest drug to take.

Michael Vick and the NFL

2009-08-28T08:40:00.000-07:00

Perhaps a few readers have heard that the monster Michael Vick has been welcomed back into the NFL (the Philadelphia Eagles). Not only that, the fans of the Eagles gave him a 'standing ovation' upon his return this week.

This is disgusting. The monster Vick was not only involved in dog fighting, a brutal sport that by definition is animal abuse, but he tortured and killed dogs who weren't 'good enough' to fight other dogs. That means that innocent dogs who wagged their tails, licked hands and faces, full of love and happiness, were tortured by electrocution, by strangling, and by being stomped to death at the hands of the monster Vick.

Yet this monster is glorified by the NFL and the residents of Philadelphia? This evil monster is rewarded by the NFL, the Philadelphia Eagles and the fans of that team?

DISGUSTING

I cannot watch a NFL game as long as the monster Vick is rewarded by the NFL. I will not watch a game, I will not watch any pre-game show, I will not buy anything from any advertiser that I know of that pays the NFL and/or the Philadelphia Eagles, nor will I allow the evil that is associated with the monster Vick into my home.

It is indeed sad that America not only allows such evil to get out of prison after only 18 months, but it REWARDS the evil that the monster Vick is.

I will never set foot in Philadelphia as long as I live, for the citizens of that town encourage and love all that the monster Vick represents. If they objected, the monster Vick would not now be playing for the Eagles.

I know my actions will not change the venality of the NFL or the Philadelphia Eagles, but I hope somehow the poor dogs who suffered terribly at the hands of the monster Vick know that someone loves them and is so sorry that they suffered. I hope somehow they know that someone fought to deny their torturer the rewards and adulation that Philadelphia is showering on the monster Vick.

Is FCR Losing its Golden Luster?

2009-08-13T19:47:00.000-07:00

It's not been too long ago that I, among many others, dubbed FCR (fludarabine, cyclophosphamide, and rituximab) as the 'gold standard' in treating CLL. The basis for that claim was the fading significance of chlorambucil (Leukeran) in treating CLL, at least in the United States. (It remains a popular drug in the UK and elsewhere.) Also, monotherapy with fludarabine has been linked to autoimmune hemolytic anemia (AIHA) a serious complication of CLL that is characterized by the development of antibodies to a patient's own red blood cells. Combination therapies such as FCR, which add other drugs to fludarabine, appear to be free of the risk of initiating and promoting AIHA.

The complete remission rates of FCR, reported primarily out of MD Anderson, are extremely impressive, and far exceed that of chlorambucil. For example, at the 2007 ASCO meeting (American Society of Clinical Oncologists, a major cancer group), MD Anderson reported on the long-term results of 300 patients who were treated with FCR at the institution. The group reported that 72% of patients enjoyed a Complete Remission, 11% obtained a nodular PR (PRn) & 12% ended up with a Partial Remission. Saving the calculation, that is a phenomenal over-all response rate of 95%. In spite of the immune suppression associated with the drug combination, infections were manageable with prophylactic antiviral, antifungal, and antibiotic drugs.

However, the long-term survival pattern showed no plateau, meaning that the rate of death did not level off at any point, meaning that most if not all patients would eventually fail FCR. Quoting the study: "Median Times to Progression (TTP) were 80 months for CR (n=216), 80 months for PRn (n=32) & 27 months for PR (n=36), with 77%, 65% and 28% projected to be progression-free at five years; projected 5 yr survival were 90%, 81% and 37% respectively."

These data are superior to single agent fludarabine, and fludarabine in combination with cyclophosphamide (FC) or mitoxantrone (FM).
(www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=36113)

The down side? Well, it is not a cure, nor does it appear to have that potential. There are some very long-term survivors, out 10 years or more. But based on projections, it is possible, if not likely, that most everyone will eventually relapse. And even in the case of those who have deep, long-term molecular remissions (data not available in the 2007 ASCO abstract, but has been reported to be about 32% in complete responders, meaning the over-all MR rate is about 24%) it is expected that they, too, will fall out of remission down the line.
(http://tinyurl.com/lgxy3q)

So, what will replace FCR as the 'gold standard'? It must be noted that this is a moving target. For decades, chlorambucil was termed the gold standard, even though complete remission rates were only about 5-10%. Then single agent fludarabine took that exalted spot.

I think that the best initial treatment for CLL might very well be high-dose methylprednisolone plus rituximab (HDMP+R). I had a discussion with a couple of nurses at UC San Diego, where Dr. Kipps has a great deal of experience with the drug combination, and they said they just don't use FCR too much any more. Instead, they do a lot of HDMP+R. I have to admit that off-handed comments by several oncology nurses isn't definitive proof, but it is very interesting that, at least in one institution, FCR has seemingly fallen out of favor.

So what does HDMP+R have going for it? For one thing, it doesn't damage the bone marrow like fludarabine does. Fludarabine has a deserved reputation for enhancing the fatal rates of infection for up to two years. This is due primarily as a consequence of prolonged neutropenia. Grade 3/4 neutropenia were encountered in FCR. That makes the patient much more likely to have a serious illness, or even death.

First developed as a salvage regime for those patients with refractory CLL (and still used for this application), patients were given five cycles of the drug combination. It was not for the faint of heart. Numerous infections occurred and deaths were reported. The regime was tailored for a less-impacted crowd; as an initial treatment for CLL patients. The duration of the regime was shortened to three cycles.

A report in 'Leukemia' 2008 reported that in patients who were refractory to fludarabine and had adverse genetics, fully 93% of patients responded to the combination, and 36% had a complete remission. This compares favorably to the FCR regime. The paper states that median survival "has not been reached after a median follow up of 40 months."
(http://tinyurl.com/m9ropo)

There are also anecdotal reports that some patients who have completed HDMP+R have begun to normalize their immune system, as reported in a previous blog post here. That is simply astounding to me; I am unaware of this happy development in anything less than a stem cell transplant.

It also should be noted that adding a Campath 'chaser' to those who responded to the drugs, and did not develop bulky lymph nodes, may have enhanced responses.
(www.geocities.com/m_mcghan/ourpage.html?20066)

Another development in CLL needs to be reported as well: 'FCR-lite'. This regime seems quite promising, with good results in spite of the reduction of the dose of fludarabine and cyclophosphamide, and an increase in the dose of rituximab. Reports are that the side effects are lessened compared with FCR, and the responses seem to be (at least initially) almost on par.

The paper states: "The OR and CR rates were 100% and 79%, respectively, using the 1996 NCIWG guidelines and 100% and 77% using the 2008 guidelines. Median duration of complete response was 22.3 months (range, 5.2 to 42.5 months) and none of the complete responders have relapsed. Grade 3/4 neutropenia was noted in 13% of the cycles of therapy."
(www.jco.ascopubs.org/cgi/content/abstract/27/4/498)
(www.medicalnewstoday.com/articles/138141.php)

It must be noted this trial was in untreated patients, most of whom had early stage CLL (only 16% had stage 3 or 4 CLL). (I'm not sure why a stage 1 CLL patient was even treated, but 40% were here.) That might be considered 'stacking the deck', and making comparisons with FCR and HDMP+R difficult if not impossible.

The bottom line: It may be premature to dethrone FCR as the gold standard, but recent advances in research suggest that we might need to rethink exactly who's on top in caring for CLL patients.

Rumors in CLL Treatments

2009-07-31T20:23:00.000-07:00

I had an interesting discussion with a CLL researcher who said that there have been some indications of a reconstitution of a patient's immune system after successful treatment.

This is big news. Of course, I don't know (and I don't think the researchers know) if this will hold up, or if the trend towards a revamped immune system will continue to total normalcy. However, as we've been often told, even in molecular remissions, the native immune system remains disrupted. This may not be the complete truth.

My feeling was from what he said was that this is in a minority of patients. But I think the true import of this development is that there may finally be some light at the end of the tunnel. I hope enough of a trend continues that a paper will be written that discusses these developments (if they remain developments) more completely. I look forward to the day!

Since infections kill most CLL patients, having a full-functioning immune system would be big news indeed.

Since this was an off-handed comment, I just don't know the particulars. However, I hope this does hold up. Certainly, this is another indication that research is extending lives. Is this an indication that, caught early enough, and treated properly with powerful, dangerous, but effective drugs, a cure might be possible?

Biggest Bang for the Donated Buck?

2009-07-31T20:12:00.000-07:00

Check this out!

http://www.bcrfund.org/howtohelp.html

Yes, a generous donor has made a challenge grant to the Blood Cancer Research Fund (yes, for CLL). So for every dollar you donate, another dollar comes from this fund and goes right to work!

Apparently this has been going on for a year, but I just read about it a few weeks ago, and haven't had time to post on it.

Seriously, folks, now is the time!

Please, rare reader, think about making a donation to Dr. Kipps and the hard-working team in CLL. I have heard from many others that cutting edge research is coming from the mind of Dr. Kipps and other talented people, all of whom depend on funding to further understand CLL.

I know times are tight, but as the article says, just $10 per month for the next year would match this grant.

(I'm not neglecting other funds myself, and I am not saying don't contribute to CLL research groups. I think right now, by doubling our donations, this is a very effective way of making our contribution go as far as possible.)

Think about it.

Addendum to "When to Treat"

2009-07-31T19:52:00.000-07:00

It did dawn on me that for those who are 11q or especially 17p deleted at diagnosis might not have a watch and wait period, but might be given treatment shortly thereafter. Therefore, there is no trend to watch before the first treatment, but there may be a trend to watch before second treatment (if it is necessary).

There are other indications for treatment as well. I must confess that I am basing my recommendation on my own experience and what I believe to be accurate. It is based also on the experiences of others and conversations I've had with people, those with a medical background and those who are just careful researchers, as well.

I confess I don't know if a reputable oncologist would initiate a watch and wait patient simply on the basis of reported increase in fatigue. Or with bothersome night sweats. Or on the basis of Rai/Binet stage alone.

I suppose I should really say that it is my opinion that if one is tracking one's absolute lymphocyte counts, and they make a radical change north (as mine did), it's a sign things are changing. People I respect have concurred with me. But, as I've said, this is not a complete picture. Perhaps it's only good for a subset of CLL patients. (But remember that night sweats and other 'B' symptoms aren't always related to CLL. Other diseases or even coming off drugs for pain can lead to this problem. Or, I understand, even menopause?)

When should I start treatment?

2009-07-25T10:35:00.000-07:00

If this isn't the most important question the newly-diagnosed CLL patient needs to ask, it's in the top five. And it's for these reasons:

1. The first treatment is most likely to give the patient the longest and best response to treatment.

2. The CLL cells haven't been exposed to any treatment, and thus generally consist of nice, 'squishy', easy-to-kill CLL cells. None of your cells have been through 'chemo boot camp', thus aren't toughened up by 'combat'.

3. The patient generally is in as good of shape as he ever will be.

4. The choices for treatment are wide-open (all things considered). The oncologist can generally offer many different treatment modalities.

So, how can the patient decide when he needs treatment? Well, I suppose the simple answer is that he can't, at least by himself. He needs to do so with the assistance and the guidance of his oncologist.

At this point, let me make it clear that my perspective comes not from a medical background, but from that of a patient who has survived over 10 years with CLL, and, more importantly, have researched the topic in some depth.

There are two proven guides to when treatment might be necessary. One is the stage of your CLL (stage 0=1 is unlikely to need treatment, but it may). The second, and over-riding one to me, is the doubling time of the Absolute Lymphocyte Count (ALC). (The count is easy to derive: take the total white blood count, and multiply by the percentage of that count that are lymphocytes. In other words, if your WBC is 100, and your percentage that are lymphocytes are 90%, then the ABC is 90,000.)

You've probably seen a number of sites and posts which offer the ability to enter in data which will then produce a graph. Excel is spreadsheet which allows one to chart blood numbers, there are others as well.

Starting with the blood counts taken at diagnosis, I recommend creating a spreadsheet and entering at least two data sets: the absolute lymphocyte count and the day the blood was taken.

I've worked with a spreadsheet from scratch, but you don't have to do that. You can download a spreadsheet ready to enter your blood numbers from CLL Topics: www.clltopics.org/YourCharts.htm .

Once you have developed a worksheet, you can add to it with each blood test. Let's assume you have fairly stable absolute lymphocyte count (other data such as the total white blood count won't work). This is typical in early CLL. Plot each value, and pay attention to the trend. To make the trend more clear, create a chart using time as the x-axis and the ALC as the y-axis.

One tried and true indication that treatment might be in order is when the absolute lymphocyte count (ALC) shows a pattern that will result in the number doubling in less than one year. (Check with your oncologist to see if this is how he views treatment decisions.)

Once you start plotting data, thing those of you are going to need treatment will see an obvious jump in ALC. The trend must hold for some period of time, or over several tests.

It is at this point that something has changed in your CLL. Perhaps you have picked up a change that causes your CLL to start proliferating at a higher rate. Perhaps for some reason your CLL cells are not dying at the same rate they were previously.

In any case, I personally think this may mark the best time to hit your CLL.

The other indicator that treatment might be considered is your stage. If you are diagnosed with a stage IV CLL, you probably have noticeable illness in terms of a low platelet and/or hemaglobin number. I'd still chart out your ALC and share with the doc to see if the disease is making a move.

Barriers to Clinical Trials-the CT scan

2009-07-21T23:01:00.000-07:00

I'm not going to write a book as I did on my last post!

Suffice it to say, some of the barriers to entry of clinical trials are listed on the last post.

I want discuss one real barrier to clinical trial entry that is easily remedied. That is the demand that participants undergo multiple CT scans to track progress (if any) in the trial.

Why is there a barrier? CT scans involve high levels of radiation, and they have definitely been linked to subsequent cancers.

The risk is low, the authorities say. But any increase in cancer risk sort of defeats the search for a cure for CLL, doesn't it? It certainly makes no sense when there is an excellent alternative: MRIs.

Clinical trials are done to look for results. The ultimate hope is a cure, because the drug in tests would be a huge success! Most likely, a more modest goal is envisioned: better results than current drugs.

Determining whether a drug is better than the standard treatment is surprisingly difficult. Drug companies can't wait around for 20 years to see if patients continue to do well (i.e. survive). Instead, they look for 'end points'. These generally include signs of tumor shrinkage or elimination. That is the reason drug companies want to check your nodes. The way most doctors are used to doing this is ordering a CT scan.

Yet we've seen the danger to the patient is real. Given a choice between a trial using an MRI and one demanding multiple CT scans, most people who are aware of the dangers of CT scans will pick the safer one, in other words, the one allowing the use of MRIs.

Why do drug companies deliberately rig their trials so people are less likely to sign up? It's a mystery, with perhaps a partial solution. Several of the drug companies I've talked to are aware of the concerns on the part of patients, and know that an MRI can track lymph node size just as well (or better) than CT scans.

Well, who then is the moving force behind this unfortunate situation? The drug companies blame the CLL researchers themselves! It is the research community that apparently doesn't care about patient safety to the point that they will allow safe alternatives to dangerous radiation exposure to patients.

I've discussed this with a few researchers in light of these claims. Rumor has it that there is a group of CLL researchers who are (pardon the expression) really anal about scans. The Germans.

I suppose we who are not German can recall the reputation the Germans have for meticulous record-keeping and administration. It apparently extends to CLL clinical trials.

Who ever is to blame, it's time the patient community help end the danger. Some of us need clinical trials if we are going to stay alive. We are sacrificing our bodies to advance science. It is incumbent upon researchers to watch out for our health. We are helping them (and the drug companies) when we sign up for a trial. They need to help us avoid doing more damage to our bodies than the investigational drug might cause.

Should you enroll in a clinical trial?

2009-07-20T20:26:00.000-07:00

Clinical trials are big business in the United States; indeed, around the world. One group estimates there are 40,000 clinical trials on-going at the present time in the US. Virtually any drug that seeks FDA approval must go through the clinical trial process. This includes already-approved drugs that seek approval for another use; an example of this is our old friend Rituxan, the first monoclonal antibody approved in the US. It is used frequently for CLL, but it was never approved for such a use; instead, it was approved in 1997 for non-Hodgkin's lymphoma. It is undergoing tests now for approval for use in CLL; that's important because any health care 'reform' will limit drug use. It may even make it illegal for Rituxan, or any other drug, to be used off-label.

Any clinical trial needs two things: a new drug or device, and bodies to test them. Cancer, as one can imagine, is chock-full of new drug applications, and clinical trials. Go to the excellent site for the government's clearinghouse for clinical trials (clinicaltrials.gov), and you'll find about (about because it changes every day or so) 23,000 trials in the US and overseas that involve some aspect of cancer.

Some trials seem almost silly. There are, for example, a number of trials examining the value of music to soothe the savage cancer patient's breast. There are some that seek to find the value that art has in calming dying cancer patients.

Mostly, however, clinical trials seek to ascertain the dangers and values of drugs in fighting advanced cancer. (There are some trials, of course, looking at treating patients early in the disease; CLL is a particular hotbed of such studies, since previous research has not uncovered a value in starting treatment early, as opposed as to when it is most definitely needed.

Search clinicaltrials.gov for CLL trials and (as of this moment) 1209 trials show up. The site seems to list trials that only mention CLL in passing; there are far fewer trials that have CLL as the main focus of study. There are probably fewer than 200 that are of serious interest to the CLL patient.

So, should you enroll in a clinical trial? That is a tough question, but, over-all, I'd recommend you seriously consider it. Why? Because every effective drug for CLL has gone through the clinical trial process, and you'd have first (or second, or third) crack at it. When you have run out of options, that is not a small factor.

(There is also the altruistic nature of trials as well. By joining, you will help future CLL patients have access to proven drugs. But studies have shown that most participant hope to have some benefit as well).

Let's say you've decided to at least look at clinical trials. Are they all created equally? No, of course not. Unless Bach or Picasso really rocks you, you might just say no to music and art clinical trials. You are not going to get cured by such a trial. But what should you look at?

I'll give you my thoughts on the subject, but remember that I'm 'only' a CLL patient, one who has (thank the Lord) outlived his projected lifespan by a number of years, and who is hanging in there as I write.

First of all, you have to decide what drug to look at. This takes research, even if it is just talking to your oncologist. I relied on a CLL expert to guide me in my choice of clinical trials, up to a point. I must admit that, while I am an expert on my own body and how I feel, the CLL expert has seen hundreds of cases, and is more of an expert on how my disease will, in general, progress.

I thought long and hard about my first trial I undertook in 2006. I researched everything the CLL doc told me were my options (and the field is pretty wide open when you are untreated). Yes, I was drowning in green tea back then, but I was still progressing, so my doc and I agreed that I needed something stronger to knock the CLL back.

I also looked at the trials his institution offered. I asked about each of them. I then searched on the top five or six that seemed as though they might be good for me. I printed out study after study, and, using a highlighter, I marked the response rate, the side effects, the burden of treatment (would I have to stay in the hospital) and so on. I then went to clinicaltrials.gov and looked at everything that seemed familiar, and a few that didn't. I had been tracking and thinking about clinical trials since I had been diagnosed some eight years before, so I wasn't unfamiliar to the terrain.

Next, I needed to make a decision about what phase trial to look into. A refresher: a phase one trial is a dosing safety trial, meaning they ramp up the drug until unacceptable toxicities are found. A phase two trial is an efficacy trial, that is, does the drug show any activity in the disease. The phase three trial compares the new drug with the standard treatment. (Placebos are never used now in lieu of treatment; it is considered unethical to withhold at a minimum the 'gold standard' treatment, though that hasn't always been the case, in the old, bad days.)

The problem with phase one trials is poetically described in another way to look at these trials: First-in-Man trials. (Many drugs have been used elsewhere, but the name tells a lot.) The phase one trial is given over a range. The first patient usually gets a dose that is far too small to do anything at all. The subsequent patients are given higher and higher doses, until bad things start popping up. Pre-clinical trials give a hint of activity in humans, since they use human cells in culture, as well as the ubiquitous mouse and rat studies.

I have undergone a phase one trial, but I try to avoid them for the reasons outlined above. If you press the trial coordinator, he or she will generally tell you what the other patients in the phase one trial have experienced. But that isn't a foolproof guide. In my phase one trial, the trial coordinator told me to expect flu-like symptoms. (This is such a common description of side effects, it's a little like telling a diner that mongoose or arctic wombat 'tastes like chicken'.) To say I had 'flu-like symptoms' was something like saying the Titanic had a little problem with an iceberg.

I puked my guts out! It was horrible. Yes, I experienced projectile vomit! It was even green, something like the Exorcist (I had a huge helping of spinach quiche the night before.) I've never had such a terrible flu, or if I had, I've blocked it from my memory to protect me from insanity. (Because of my, and others, experience, they now give anti-emetics, or drugs to quell nausea. Thanks, guys, what took you so long?

I prefer the phase two trial. Generally, in a phase two trial you are guaranteed to get the drug (not so in the phase three trial, which is, after all, a comparison trial). The maximum tolerated dose has been established. Anti-nausea drugs have been prescribed. Dosing schedules may been worked out, more or less. Results have been published on the experiences of the first trial (yes, my experience is now part of the record...). You have a better idea of the risks and benefits of the trial.

The phase three trial, as I mentioned above, has the huge disadvantage of not giving the investigational drug to all comers. This is very important in a serious and fatal cancer such as CLL. Why, you could get the standard treatment without going through the qualification process, all of the scanning, all of the prep work, and so on. Some trials do try to 'sweeten the pot' by offering the new drug to 2/3 of participants, instead of a 50/50 split. This is much better for the patient, but this isn't a common practice, for some reason. The best option of all is to give the drug to everyone, and compare their results with historical controls. Hardly any researcher likes this option, which is too bad for the patient community.

My next post will deal with the very real barriers to patient's signing up for trials. It seems to me that not enough researchers are concerned with how we feel about the clinical trial process.

The Bottleneck for New Drugs is the FDA

2009-05-30T09:03:00.000-07:00

Let's face facts: The FDA is a bureaucracy that is still a-glow in the protection of many Americans during the Thalidomide baby birth defect debacle. That protection came, ironically, by a bureaucrat stalling on doing anything in approving the drug. After this woman sat on her hands for months and months, the world learned of the terrible birth defects occasioned by Thalidomide.

The FDA has taken that lesson to heart. Do nothing is the wisest and safest course. If you approve a drug or device, such as Vioxx or breast implants, and there is even the hint of health problems, you will be hounded by lawyers forever. And the drug companies, which put out largely a safe product, will be tarred by the negative publicity surrounding the drug.

As part of the massive deficit spending by this administration, some money is supposed to trickle into cancer research. As the following editorial points out, the last time money was poured into reaseach, it all 'disappeared into a thousand tiny holes.'

The author of the following piece argues that the FDA has to do better this time. Instead of waiting years and years for drug efficacy to be demonstrated by over-all survival, it needs to accept surrogates for effectiveness, such as progression-free survival (PFS) as good enough to move a drug forward.

The Next Front in the War on Cancer
Faster clinical trials are critical if we are to save more lives.

By MARK THORNTON

On Tuesday, President Barack Obama announced a massive initiative against cancer. "Our recovery plan will launch a new effort to conquer a disease that has touched nearly every American, including me," he said in his speech to the nation, "by seeking a cure for cancer in our time."

Specifically, the president was referring to a provision in his stimulus bill that will direct a tranche of funding to the National Cancer Institute (NCI). The money will come from the $10 billion that's being steered to the National Institutes of Health, and it will, for the next two years, match the surge in spending on cancer that occurred between 1999 and 2003.

But despite the lofty goal set by Mr. Obama, it appears that the NCI is not mapping out a specific plan or strategy on how to most effectively use its new money. It is simply going to pour more money into the cancer research community.

In 1998, a new day was dawning in cancer research. The genomic codes of cancer were being broken, and an explosion of new vulnerabilities was being discovered that had the potential to reveal hundreds of new "drugable" targets. The hope then was that this would quickly produce a cure.

The dream was that this dramatic funding increase would break the back of cancer.

It didn't. Now that the money has disappeared, the diagnosis of cancer is no less fearful in 2009 than it was in 1999.

Read the rest at:

http://online.wsj.com/article/SB123569839480689223.html

Our lives depend on doing a better job, folks!

Rituximab Isn't Sugar-Water

2009-05-25T17:26:00.000-07:00

Many CLLers use rituximab to treat their CLL. It is preferred to chemotherapy drugs such as fludarabine because it seems by comparison to be relatively non-toxic (except, of course, for the acute infusion reactions).

This paper in Blood points out the chilling fact that rituximab has been linked to a serious brain disease, progressive multifocal leukoencephalopathy (PML).

Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

Kenneth R. Carson, et al

Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment.

We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008.

Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients).

Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

http://tinyurl.com/ofyubj

The other great disease which causes immunosuppression of course is AIDS. These patients can be struck by reactivation of the JC virus. It seems less common in CLL patients, at least it is not described in the literature to any great extent.

You don't want to get PML. It is caused by the JC virus, which is present in almost all adults. It lives in the body, harmlessly, for years. In cases of immunosuppression, occasionally it will attack brain tissue, leading to gross mental deficiencies, and in most cases, death. See the wikipedia article on the JC virus:

http://en.wikipedia.org/wiki/Progressive_multifocal_leukoencephalopathy

It should be noted that since all CLL patients are immunosuppressed, the disease may strike with or without rituximab. However, those using rituximab seem to be at a higher risk of developing the disease. Cases of PML were probably 'hidden' in the general population of immune-deficient patients such as those with CLL, so it was not clear and evident. In those with other diseases who are not immunocompromised, these cases are so atypical as to be suggested to be caused by the rituximab.

"Simply Doomed to Achieve Complete Remission"

2009-05-25T16:09:00.000-07:00

I don't know who Vladimir Savostianov is, but he claims to be a hematologist in Minsk, Belarus, and he claims to be able to put up to 60% of CLL patients into prolonged complete remission using old drugs and techniques, regardless of stage (though the patient must be treatment-naive).

He has posted an interesting protocol on his blog, http://dr-savostianov.blogspot.com/2008/08/chronic-lymphocytic-leukemia-treatment.html

I confess that I find his English to be of the sort of "Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan". However, one needs to accept the premise that his therapy for CLL is interesting and worth a second look, primarily because it is cheap and, if verified, provides a vastly superior complete remission rate than most therapies, with the exception of FCR.

He apparently begins his therapy with prednisone and radiation to the tonsils, spleen, abdominal lymph nodes, and liver. He then administers chlorambucil. He believes that knocking back the pool of CLL with the prednisone and radiation permit the chlorambucil to deal a heavy blow to the CLL. He warns, however, that any departure from his schedule will leave the patient with a case of drug-resistant CLL.

He says this technique is free of immunosupression, and if it does occur, it is a simple matter to remediate.

Make up your own mind, but there is enough sense in this that perhaps there is some merit to it. Certainly it does not depend on expensive drugs such as rituximab, fludarabine, and Campath.

Approval sought for Rituximab in CLL - Why?

2009-05-22T13:02:00.000-07:00

Doesn't this sound like the biggest non-news of the month? Rituxan is used routinely to treat CLL, both in combination and alone, though the latter is less frequent.

The following article is important for two reasons. First, it lets the companies advertise rituximab for use in CLL. There are competitors coming, namely Arzerra (HuMax-CD20), which should be approved for CLL this year, as well as several other CD20 drugs.

Secondly, with Obamacare looming, it is likely that off-label drug usage will be curtailed if not eliminated totally. With CLL such an important revenue source for the drug companies, it would behoove the company to have as many applications as possible for the drug already in place.

Here's the press release:

Genentech And Biogen Idec Submit Applications To The FDA For Rituxan For Most Common
Article Date: 22 May 2009 - 4:00 PDT

Genentech, Inc. and Biogen Idec (Nasdaq:BIIB) announced that the companies submitted two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for Rituxan® (rituximab) plus standard chemotherapy for people with previously untreated or treated chronic lymphocytic leukemia (CLL). The companies will request a priority review, and if granted, anticipate the FDA will make a decision within six months.

The applications are based on positive results from two of the largest global Phase III clinical trials conducted in patients with CLL. The randomized, comparative studies, known as CLL8 and REACH, showed that Rituxan plus standard chemotherapy for CLL extended the time patients lived without the cancer advancing (progression-free survival or PFS) compared to those receiving chemotherapy alone. In CLL8, previously untreated patients who received Rituxan plus chemotherapy had a 69 percent improvement in PFS (41 percent risk reduction, hazard ratio=0.59; p<0.0001; 95% confidence interval: 0.44,0.72) compared to those who received chemotherapy alone.

Is your Health Care Practitioner Reading Your Blog?

2009-05-13T20:23:00.000-07:00

A couple of years ago, I got a huge shock when I went in for some routine blood work in the big, fancy CLL center, and noticed my nurse was acting kind of funny. She mentioned something that I had posted on-line in one of the CLL lists. I had complained about something, and she was defensive about it. I realized that she, or someone else, had been reading my posts about my clinical trial!

For some dumb reason, I thought the only people who would read CLL group messages would be other patients. To be honest, I thought that oncologists and nurses were way too busy to even think about searching on the terms of a trial to see what patients in that trial were saying.

I've known for a long time that financial creeps troll the patient groups, looking for any information they can use to make financial decisions. Although less than honorable, I guess it's something that wouldn't surprise me too much.

But to have my health care practitioner looking for posts on a clinical trial floored me.

I am much more careful now. If I have anything at all even remotely critical to say, I say something like, 'a famous CLL doctor', or a nurse at one of the top CLL centers.' I'll use it every time I didn't want a particular doctor to read what I said about him.

After all, there is no reason at all to get your doctor or nurse mad at you.

The web is a huge party line. (Older folks are at least a bit familiar with the concept of the telephone party line. We used to have one. It was cool, but inconvenient at times.) Be careful what you say!!!

Alternating EGCG and Curcumin - An Update

2009-05-12T20:15:00.000-07:00

I decided to experiment a bit on myself, based upon a paper published recently that showed that EGCG and curcumin can have synergy, but only after CLL cells were washed, and the EGCG was given prior to the administration of the curcumin.

Hmmm. Easier to experiment with this than cancer vaccines or ofatumumab (Humax-20). Since I don't have a lab with a newly-minted PhD., I am restricted to trying out substances that are easily available. There are a few out there, and that's why I keep perusing the medical literature, looking for any little angle that might help slow the runaway train that is my CLL.

Well, I alternated the two drugs, changing them every 24 hours. I didn't 'wash' my cells, but I did remain hydrated, which doesn't wash cells but is important to all of us, anyway.

The results have been less than spectacular. My counts are pretty low after my four cycles of FCR, ending early because of persistent neutropenia. (The famous doctor at MD Anderson who said he could give me three years with FCR was off by about 2.8 years...)

My main gauge of success/failure of any treatment is, number one, the WBC count, and two, the size of my massive abdominal nodes. Since my counts are fairly low, I really only have my abdominal node size to go by. I sort of can tell whether things are shrinking or not by how tight my pants are.

I used to be a not-very-svelte 36 inch waist size (there was a time when a 32 waist was loose on me; I think that was the Nixon administration though). After I developed the 11q deletion after my HDMP+Rituximab (high dose steroids with high dose rituximab), my waistline started to morph out of control. After the 36 inch pants became too tight, I opted for the 38, then the 40, and then the 42. So in one year, I gained six inches in waist size without gaining an ounce of over-all weight.

Bummer!!!

Sad to say, even after about three weeks of the EGCG-curcumin-EGCG shuffle, my pants weren't a bit looser. So, I deem the effort a failure.

However, I did feel pretty good during the time, no night sweats, no hot flashes, no increase in fatigue, and my counts didn't suffer.

Why didn't I see better results? Two reasons, I think. First, I have very advanced, stage IV CLL. I've been fighting poor-prognosis CLL for over 10 years now, and I've developed, I'm sure, lots of bad chromosomal changes and increase chemo-resistance.

The second reason, probably much less important, but important nevertheless, is the abysmal bioavailability of both EGCG and curcumin. It's one thing to dump a teaspoon of pretty curcumin in a witch's brew of CLL cells; it's another to achieve an equivalent level of curcumin in one's bloodstream.

The usual trick is to take curcumin with bioperine. One must be careful not to overdo this compound. Too much apparently isn't good for you. The other thing is to dissolve the yellow, highly-stainable curcumin into warm or hot coconut milk. The high fat content of the coconut milk definitely does dissolve this spice. I also add a little bit of alcohol to help dissolve the product, usually amaretto. The latter adds a nice flavor to the concoction. Margaret swears by the C3 complex that comes from Sabinsa corporation. A number of companies use that product to make their offerings that are available retail.

The EGCG I usually use is Teavigo. This is available from a variety of suppliers; I purchase mine from The Vitamin Shoppe, which has a reasonable price for the product, and sometimes offers free shipping for a certain dollar amount of purchased product. I add another EGCG extract with a different formulation just to cover all my bases.

Both are supposedly best taken on an empty stomach. I will tell you that the EGCG is very rough on my stomach, so I do eat something perhaps fifteen minutes after swallowing the pills. It will make me throw up if I wait any longer.

My 'guru' on curcumin is Margaret, who posts on her own Multiple Myeloma blog. She's an older hand at the curcumin business, and has really benefited by using the spice. Her blog, 'Margaret's Corner', is one of the blogs listed on the right side of this blog post. She is a wealth of information on curcumin, including a section on how to get rid of curcumin stains, which I will attest gives anything you touch after you've pulled apart the capsules a very bright, vivid yellow, which will not wash out.

I was taking to wearing an old, ratty robe while making the curcumin mess. My wife gave this robe a pretty pink color after washing the formally white terry cloth with some red shirts. Now this pink robe has several splotches of screamingly yellow curcumin stains on it, that defy all attempts to remove them.

I suppose my entire digestive tract from top to bottom is now fluorescent yellow in color. I wonder if that would show up on an MRI?

Cutting healthcare costs

2009-05-12T19:59:00.000-07:00

My antenna go up when I hear this phrase. It reminds me of the 'NICE' organization in the UK. This is the group that 'evaluates' drugs to see if they are 'cost effective'. Obviously, when health care is just another budget item, competing with schools, defense, and welfare expenditures, there is great pressure to hold down costs.

The track record of NICE when it comes to cancer drugs is poor. UK residents just don't have the panoply of therapies available in other countries, including the United States.

Everyone is in favor of cost-effectiveness, right? Well, if you are, remember that CLL patients are a very small lobbying group, and drugs such as Rituxan and Campath are very expensive.

If you are concerned about the treatments you will be getting in the future, pay very close attention to the details. It's one thing to say you are going to cut health care costs; it's another when the savings comes from denying care to you.

I'm reserving judgment until more is known about the president's plan. I will be seeing if health care will be changed for the worse.

(In my opinion, the best thing would be to increase spending and make a serious move to start curing cancers. Imagine how much more money cancer patients would be saving the health care system, and paying into the entire economy, if they could be free from the illness and pain of cancer!)

Kanzius Cancer Machine is Effective Against CLL Cells

2009-05-10T18:59:00.000-07:00

Former broadcast engineer and radio station owner John Kanzius devoted his final years to the development of a 'cancer-killing machine.' Mr. Kanzius' technical background in radio, along with an accidental exposure to radio waves that heated up the coins in his pocket, wondered if the power of the radio waves could be harnessed to kill cancer cells. He says that he was motivated to do something to help cancer patients fight their cancers, after getting off on a pediatric cancer floor in a visit to MD Anderson, and witnessing first hand the suffering that cancer inflicts on young patients.

He was visiting the renowned cancer facility in order to undergo treatments for his own cancer, chronic lymphocytic leukemia (CLL). Although originally believing the cancer-killing properties of radio waves would be limited to solid tumors, Mr. Kanzius couldn't help but wonder if it could help cure his own cancer. Unfortunately, he passed away in February, 2009, as preliminary testing of his invention was underway. He always knew that it was a long-shot, but he reserved hope that he might benefit from the machine he created.

Meanwhile, research on the Kanzius invention continues. Doctors at MD Anderson, who were initially intrigued by the possibilities of marrying radio waves and nanoparticles, have made progress. The latest news released on May 8, 2009, demonstrates that the Kanzius machine can indeed kill CLL cells.
Reported by David Bruce and published on GoErie.com, the external radiofrequency generator can kill CLL cells while not significantly damaging normal cells, an important finding.

This finding was ascertained in December, 2008, using the cancerous cells of 19 CLL patients. However, the results are only a tantalizing hint at the possibilities of the machine. Dr. Steven Curly of MD Anderson, who has been spearheading the research effort, said that the CLL killing was probably due to the heating of the cells, which are tagged with gold nanoparticles, attached to a monoclonal antibody that attaches to CLL cells.

So, another step forward. According to the article, the percentage of CLL cells killed was not enumerated, so I can't tell how effective the treatment was, nor can I tell from the article how long the duration of the RF field exposure was, what antibody was used (I'm assuming a rituximab-like MoAB), or any other parameter that would be vital to know.

I've read elsewhere that theis RF generator can heat cells up to 600 degrees or so, plenty warm to kill them. Of course, non-CLL B lymphocytes express the CD20 marker, so it would seem that the machine could potentially kill every cell that carried sufficient gold nanoparticles.

Ideally, this would work as a 'super-rituximab' that, as long as a cell expressed the CD20 marker in sufficient quantities, it could be killed by the machine.

For the full news article, go to http://www.goerie.com/apps/pbcs.dll/article?AID=/20090508/NEWS02/305089932/-1/NEWS02

For more information about the Kanzius Cancer Machine, go to http://www.kanziuscancerresearch.com/

Cholesterol and CLL-How's it Going?

2009-05-01T20:22:00.000-07:00

My one reader will remember that I've decided to postpone killing CLL cells by dying. One thing to do this is to deny the cells the means with which to grow. Cholesterol levels are dysregulated by CLL, possibly because the rapid growth of the clone (that is, the CLL cells) require cholesterol to form the cells themselves. That is one theory, at least.

Believing that reducing cholesterol in my diet and reducing it further by adding a bit of fiber to my diet probably won't hurt me, I embarked about a month ago on a fiber-added diet. I must report that the results of my little experiment is inconclusive at best.

One of the 'problems' is that, at the present time, my WBC is quite low, below even the normal range due to my recent bad experience with FCR (fludarabine, cyclophosphamide, and rituximab) for my CLL. So I can't report a huge drop in the WBC numbers. I can look at the ratio of neutrophils to lymphocytes (the two largest components of the white blood count). It has bounced around, but still shows too many lymphocytes. The ratio has not changed for the better.

So, I am not bouyed by these results. I will continue to add a teaspoon a day to my diet, because I probably don't get enough fiber as it is, and adding a bit won't hurt. Didn't seem to help, don't think will hurt.

I'm thinking on embarking on a different CLL journey in the near future; alternating EGCG with curcumin. A recent paper shows that the combination seems to work better than either does alone.

More later.

Patgient Dies after Using Allopurinol with Treanda

2009-04-29T23:09:00.000-07:00

This is a surprise to me; hope word gets out quickly!

http://www.bizjournals.com/philadelphia/stories/2009/04/27/daily20.html

Tuesday, April 28, 2009, 2:34pm EDT

Following patient death, Cephalon warns of using Treanda with allopurinol

Philadelphia Business Journal - by John George Staff Writer

Cephalon is updating the prescribing information for its cancer treatment drug Treanda to include a warning about the use of the drug with allopurinol, according to documents filed with the Securities and Exchange Commission on Tuesday.

According to the filing, the Frazer, Pa., biopharmaceutical company identified two cases of Stevens Johnson syndrome in patients treated with Treanda and allopurinol — one of which was fatal.

Allopurinol is used to decrease levels of uric acid in certain cancer patients.

Stevens Johnson syndrome is a rare, and potentially deadly, skin disease.

Treanda was approved last year by the Food and Drug Administration as a treatment for chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

“Although the relationship between Treanda and Stevens Johnson Syndrome cannot be determined, there may be an increased risk of severe skin toxicity when Treanda and allopurinol are administered concomitantly,” Cephalon (NASDAQ: CEPH) stated in its filing, adding that allopurinal is known to cause the syndrome.

The updated prescribing information is expected to be implemented in early May, the company said.

Mexican Swine Flu Migrating, but seems mild

2009-04-28T23:44:00.000-07:00

The pandemic is 'past control' according to the WHO, but so far, it is proving to be remarkably mild in the developed world. Mexico has seen over 100 dead. To keep that in perspective, tens of thousands Americans die each year on average from the garden variety of the flu.

As a barometer, Google News has bumped the story from the headlines, from the sidebar, to related stories below the fold, so to speak.

I think everyone is mystified, but thankful, that the flu so far is very, very mild, except in the country in which it started.

Updates on Mexican Flu

2009-04-26T23:30:00.000-07:00

The potential for a pandemic continues, though governments have finally taken action. In Mexico, the government has taken positive steps to halt the spread of the disease, though actions come after the disease has been found in several other countries, particularly the United States.

Over 100 people are now dead in Mexico, the apparent epicenter of the flu. No one has reportedly died in the United States, and many of the victims appear to be in their teenage years. The disease has been characterized as 'mild' in the US, with all victims apparently on the mend, or at least not getting seriously ill. Whether that continues remains to be seen. It is possible that the Mexican flu has gotten a foothold in that country, and authorities have been slow to respond, while in the US with its superb medical system, doctors have been treating appropriately, and early. The general better health of Americans may also play a part, in my opinion. The disease has seemingly been appearing (so far) only in people who have recently returned from Mexico. These people are wealthy enough to travel, and probably in good health, since sick people generally don't wish to travel.

Chronically ill people in the United States need to be hypervigilant. This means avoiding crowds, staying away from coughing and/or sneezing people, and washing their hands frequently. I personally would suggest considering not going to work tomorrow and in the next few days or weeks, especially if the Mexican flu has been detected in your city. I also suggest avoiding or limiting contact with children or teenagers in school, since that is a perfect environment in which to foster the spread of this serious disease.

I still work, and live in Sacramento California where a possible case was just discovered in a student who recently came back from a trip to Mexico. His school has been closed as a precaution. I may still go into work, since I have an office with a door that can close. I purchased a wall-mounted germ sterilizer, which I hope will help kill any viruses that sneak in under the door. If the flu seems to be spreading in Sacramento, then I will stay home. I also will discuss with my supervisor my need for precaution, and explore the possibility of working from home, something my employer has refused vehemently to date. I do have plenty of sick leave and vacation, which I will not hesitate to use.

As the old television program advised, "People, let's be safe out there".

Sobbering Events - The Mexican Flu Gains a Foothold

2009-04-25T20:22:00.000-07:00

I'm watching in morbid fascination as the potential of a global pandemic, with resulting illness and death, spreads from the Third World to the First across a porous border.

As I write this, Mexican Flu cases have appeared in California, Texas, Kansas, and New York. So far, no deaths linked to the flu have been reported. It will likely not be long before we learn of the first death of an American to the Mexican Flu.

For CLL patients, and others with serious, life-threatening conditions, this comes as frightening news. The Mexican Flu is eerily similar to the Spanish Flu pandemic of 1918, killing healthy young adults (20-40) rather than the usual children and elderly populations.

The specter of bioterrorism has already been raised, but it doesn't take a terrorist attack to bring the potential of such a calamity to our world, already battered by a severe economic downturn. You'd think someone had it in for us. Maybe they do.

The misery of the Great Depression was worsened by a long drought resulting in the Dust Bowl. We now have a potential pandemic in the midst of another serious money panic. Do these things go together.

The President of Mexico has now exercised emergency powers. This comes as Mexico failed to respond with the first inklings that something out of the ordinary was going on. Only when the First World (The US and Canada) were able to analyze the genetics of the victims in Mexico did everyone realize there was a flu that seems to meet all of the requirements of a pandemic: human-to-human transmission, humans can become infected with it, and the populace has no immunity to it. In my opinion, these conditions have already been met.

I will be interested to see what happens to the stock markets of the world on Monday. If the news continues to get worse, a nascent recovery will die a quick and early death.

The government claims they are ready to stem a pandemic quickly. We'll see how this pans out.

Meanwhile, keep doing what you should have been doing all along; wash your hands frequently, avoid crowds, avoid sick people, cover your nose and mouth while sneezing or coughing.

A bit more on fasting before chemo

2009-04-19T09:01:00.000-07:00

I neglected to put a citation in on the post about fasting before chemo. I can't seem to find the reference at the Proceedings of the National Academy of Sciences website, though.

Here's a news blurb on the subject if you want to read a bit more on it. The technique may protect healthy cells more than kill cancerous ones.

http://health.usnews.com/usnews/health/healthday/080401/fasting-before-chemo-protects-healthy-cells.htm

The article quotes a researcher at the University of California, San Diego who cautions that not enough is known in the human population to predict if this technique would be effective. There are some cancers, he notes, that some cancers have already altered metabolic functions in normal tissue already, and fasting might not add anything to the current treatment regime.

Interesting to note, though. I wonder if any CLL researchers have an opinion on this now, or if they will take refuge in the all-purpose answer, "it's too soon to know yet."

For Americans Only

2009-04-14T22:49:00.000-07:00

It's a few hours before April 15, a date heavy with meaning for Americans. It's the day federal and state income taxes are due. Despite suffering from cancer, or going through chemotherapy, the IRS wants its money, and it wants it NOW!

I have somewhat of a complicated return, so I've in my third week of working to get this monster done. It's nip and tuck whether I can finish on time.

On the other hand, I've never failed to get at least the federal return in on time. I hope I stay healthy enough for one more day...

Should you fast before chemo?

2009-04-12T14:45:00.000-07:00

There is evidence that you might be doing yourself a favor it you do.

Me? I'm so addicted to food that when I fast, all I think about is food. I could fast one day. Two days? I've had to do it before a colonoscopy that I had late in the day one time. All I could think about was food.

I think it would be worth a try!

I'm through with FCR, so this advice comes a bit late for me.

When it's your life, this might be something to at least run by your onc doc.

Feeding the Beast

2009-04-07T22:36:00.000-07:00

If I dropped dead tomorrow, my cancer would be cured. Sounds kind of a stupid thing to say, but let's consider it a bit.

Once my heart stops beating, the CLL cells are going to soon be feeling the pinch. Nutrients are going to stop coming along, the blood flow bringing oxygen and taking away carbon dioxide simply won't be there. The protective vitamins such as vitamin C the cancer cells use to fend off death are going to be used up, and no longer serving a purpose. The CLL cells begin to die.

Obviously, this is a drastic (but 100% effective) CLL cure. Can we use this impractical information to our advantage? I think so.

We can perhaps slow the growth of the CLL clone by denying them the stuff of life. With our limited knowledge (we don't know, for example, what drives the CLL cells to merrily proliferate until it kills us, and it), we can't cure CLL by 'gentle means', but perhaps we can slow its growth.

And since CLL is an indolent (slow growing) cancer, with a potential lifespan of more than a few years, slowing the growth may mean months or even years more of good quality of life. This means, perhaps, more of us will be around when truly effective treatments are finally available.

I'm going to discuss one of those vital constituents as I see them, that the CLL cells require to madly and indiscriminately split and split and split. That's cholesterol.

Several papers have been published that point out that the standard cholesterol tests are not a valid indication of the cardiovascular health of the CLL patient (http://tinyurl.com/dha4hc). It seems that both high-density lipoprotein, HDL (the 'good' cholesterol) and low-density lipoprotein (LDL, the 'bad' cholesterol) is decreased in the CLL patient as the disease progresses.

Consider this paper in PubMed: http://tinyurl.com/dmegog. It asserts that cholesterol levels are reduced in progressive blood cancers including CLL, and that cholesterol levels rise when there is a response to chemotherpeutic intervention.

It's tempting, then, to conclude that the rapidly proliferating CLL cells 'sop up' large amounts of cholesterol to support their indiscriminate breeding. It may follow, then, that limiting the amount of cholesterol available for these cells to grow might slow the proliferation down.

I'm not aware of any studies that have tested this idea in CLL, but the idea has been floating around for some time. It's been known for years that high cholesterol is a risk factor in the development of cancers, but as far as lowering the levels as a means of slowing cancer's growth, much less is known.

There is one interesting paper, though, that concludes that the use of one type of statin drug (which is designed to reduce cholesterol levels), simvastatin, seemed to cause a slowing of the growth of the clone (http://tinyurl.com/cbzaac). Ironically, it was noted in the paper that some 40% of this very small sample of patients, went on to require treatment the following year. It is unclear from the abstract whether these four patients were the same ones who had noticable effects on their CLL clones. The apparent conclusion these researchers reached was that the use of statins may actually increase the need for treatment. The very small sample size makes reaching that conclusion difficult.

It seems reasonable to consider moderating the amount of cholesterol coming through the diet. The body is perfectly capable of manufacturing enough of the substance to meet the needs of the brain and body without necessarily consuming it.

This means going on a low cholesterol diet, exactly the same as one would adopt if one was concerned about heart disease. Low saturated fats, avoiding all sources of cholesterol in the diet, lean proteins, use of good fats in lieu of 'bad' fats, and so on. There are plenty of these diets and advice elsewhere on the web.

Another way of lowering cholesterol is to eat a higher-fiber diet. This includes both soluble and insoluble fiber. By increasing the bulk of the stool, the amount of bile acids excreated is increased. And since we know that these substances contain cholesterol, this effort can decrease cholesterol further.

We can't go too far, because a certain amount of cholesterol is necessary in the body, so I'd talk it over with your doc, and track your over-all cholesterol level.

Maybe it would have a slight, but real, effect.

Waiting for BMB Results

2009-04-04T05:10:00.000-07:00

I had another bone marrow biopsy last Wednesday, March 25. I can't count how many I've had, perhaps nine? For some reason, they've gotten increasingly painful. When I had one at MD Anderson, they told me I needed some sort of pain-killer, so that's what I asked for this time at UC San Diego. I got a prescription the day before from Dr. Kipps. It worked pretty well, I had percocet. They told me to take it when I got to the clinic, but I worked out that the maximum pain-killing aspect of the drug was at about one hour. That will be useful information if I ever have a BMB again.

I don't have results. Dr. Kipps has held off with any thoughts of other treatment until we get the results. I would have thought I would have heard about the results by now; perhaps he just doesn't want to give bad news?

I've had somewhat of a hard time dealing with my failure on FCR. My blood numbers are OK, a little low, but OK. However, the percentage of the white blood count that are lymphocytes are going up, and the percentage that are neutrophils are going down, obviously a poor sign.

He mentioned getting a Neulasta shot on Wednesday, but I forgot about it and the physician's assistant also apparently forgot about it. I have a call into Sheila Hoff, but have not heard back from her. I would I guess (now) get the shot in Sacramento, since it would be ludicrous to fly back down there for a shot.

I wish I had remembered, not that they shouldn't have arranged it themselves. Failure all around.

Cruelty to Animals - Snail Bait

2009-03-22T14:02:00.000-07:00

Sorry to depart from the usual topic, but I just witnessed one of the most horrible things I've ever seen.

We have our dog in the vet, recovering from a splenectomy (yes dogs get them as well).

There was a beautiful, young, chocolate-colored dog in another pen. He was restless when I first walked by him, but despite being on anti-seizure medicine, he was getting more and more restless. As I was visiting my dog, and could more clearly see him, I noticed he was basically having full, constant, convulsions. His eyes were staring straight ahead, and his limbs where flailing around as if his whole body was in relentless, terrible motion. It was one of the most horrific things I've had to witness.

I overheard the vet techs talking that they had given the maximum dose of the anti-convulsive drug that they could. He was getting worse and worse, they said. The dog could not swallow even a drop of water.

I asked the vet tech standing nearby what had happened. She said that the dog had eaten snail bait.

I've since found out that snail bait contains metaldehyde, a toxin that is poisonous to animals, wildlife, and children(!). It is flavored with molassas to be attractive to snails. You can imagine what a young puppy would do when there was tasty 'meals' spread around the back yard.

Why this product is permitted to be sold is beyond me. Obviously, the poor dog's owners cared about their animal, because they took him to the emergency vet. Yet they apparently didn't read the small warning label on the back that warned against putting the product where dogs and small children could find and eat it (yes, children have died from eating this crap).

There are other snail control products available that don't contain metaldehyde. And there are of course other control methods that don't subject animals to a slow, painful death.

Seeing that poor animal suffer such a heart-breaking event was enough to be seared in my mind as long as I live. If others could see that dog, I wouldn't believe that metaldehyde wouldn't be banned immediately for at least residential use.

PLEASE PLEASE PLEASE don't use this product where pets, wild animals, and even children could encounter it. This is not a painless death. It is torturing an animal to death.

Stable, so far

2009-03-19T10:13:00.000-07:00

Two plus months from my last FCR cycle, my marrow is damaged, but I am doing OK in spite of that. I've managed to avoid infections (knock on wood) and am working and carrying on a relatively normal existence.

I still have low platelets, low WBC, am neutropenic, but as of the results of the last blood test I've seen shows, the hemaglobin has come back and is now in the 12.5 range, which is a lot better than the 7.9 range I was in last fall.

I see Dr. Kipps later this month. I'll have a BMB and get his usual thorough exam. I know I have not had a molecular remission, nor a complete remission, since I still have enlarged nodes. We will see what kind of partial remission I'm in.

One unfortunate note is that we are dealing with a sick dog. He has been diagnosed with hemangiosarcoma, which is a cancer of the blood vessel cells. He has a massive spleen that could rupture with fatal results at any time. We've been offered surgery with the hope he may live another few months, but since he is 16, has an undetermined secondary mass in his stomach, we probably won't put our old guy through that.

Spring has come early again to Sacramento, with the fruit trees blossoming with all vigor.

Vitamin Might Help Boost Neutrophil Counts

2009-03-07T11:23:00.000-08:00

Anybody seen this one? This is an interesting idea. I tried reading the abstract of the paper itself and I must say I would not have drawn this conclusion, but I didn't read the full paper, so...

Niacinamide is a form of vitamin B3, and is generally found to be safe even in relatively high doses. Caution is called for, though. It's a good idea to check with the doc regarding the use of this or any other supplement. Also, the increase in counts is temporary (darn!). It may help us be safer from infections, though.

I hope there are more studies in this area. Neutropenia is a serious problem that (obviously) can kill.

The doses cited in the paper work out to between 750-1500 mg for a 165 pound man. The RDA is only 16 mg, so this qualifies as more medicine than supplementation. Also, niacin, the other common form of vitamin B3, has been linked to the growth of new blood vessels in the tumor. Tumors can't grow past a certain point without vascular support. This is true even in CLL, since lymph nodes need new blood vessels to grow, and increase microvascularization in the marrow has been linke to CLL progression.

Any comments?

**************
Vitamin B3 Fuels Neutrophil Production 2/23/2009

As the first line of defense against invading microbes, neutrophils
are the “foot soldiers” of the innate immune system. Upon release
from the bone marrow, neutrophils circulate in the blood for only a
few hours before homing to peripheral tissues where they survive at
most for 2 or 3 days. To keep up with the heavy demand for these
short-lived cells, a normal healthy adult produces approximately 10 to the 11th power
neutrophils each day and up to 10 times that number in the setting of
acute infection.

Cancer patients undergoing chemotherapy often experience disruptions
in neutrophil homeostasis, which places them at increased risk for
infection. The ability to boost neutrophil production with
recombinant granulocyte colony stimulating factor (G-CSF) has
revolutionized care for patients with chemotherapy-induced febrile (fever)
neutropenia. However, the molecular mechanism by which G-CSF induces
myeloid differentiation remains poorly understood.

A team of researchers at Hannover Medical School in Germany recently
reported a major breakthrough in neutrophil development that may have
important clinical implications. Upon binding to its receptor on the
surface of myeloid progenitor cells, G-CSF turns on an enzyme that
converts intracellular vitamin B3 (nicotinamide) into an activate
metabolite (nicotinamide monocleotide). The researchers found that
this is the rate-limiting step in a signal transduction pathway that
triggers granulopoiesis.

Addition of vitamin B3 or its precursor induced granulocyte
differentiation of cultured hematopoietic stem cells. Administration
of high doses (10-20mg/kg/day) of vitamin B3 to six healthy
individuals resulted in significant increases in neutrophil count over
a 7 day period and a return to physiological cell counts when vitamin
B3 was withdrawn.

These findings identify a new role for vitamin B3 in granulopoiesis
and beg for clinical trials to evaluate the use of vitamin B3 either
alone or in combination with G-CSF for the treatment of neutropenia.

Source

Skokowa J, Lan D, Thakur BK, et al. NAMPT is essential for the
G-CSF-induced myeloid differentiation via a NAD+-sirtuin-1-dependent
pathway. Nat Med. 2009;15(2):151-158.

It's Official...I'm off FCR

2009-02-26T00:15:00.000-08:00

I met with the local onc doc at UC Davis, and she told me there was no point in continuing to wait while my marrow struggled to make neutrophils. They have just not recovered from the fourth cycle in January.

She said she would schedule an MRI to check the abdomen. However, I know the nodes never were significantly reduced by the FCR, though I did have a response even there. Just not enough.

My response in the blood/marrow was good, I guess, though I have been mired in neutropenia land for almost two months.

Knock on wood and prayers...I have not been sick with an infection, though every tiny cut gets infected and it takes forever to resolve them. I have been dealing with gastric problems for years, and that has not improved either.

I also with have a bone marrow biopsy next month with Kipps. I will see how terrible my marrow is.

After a nice eight-year really non-eventful life with intermediate risk CLL, my cancer has not been kind to me at all.

On the positive side, the number of trials for CLL continues to increase, and there are a number of theories out there that sound really promising. I just don't know if I'll be around to get to try any of them...

Going on from here

2009-02-20T10:06:00.000-08:00

Since my counts haven't recovered, we've stopped pretending that I'm going to get my fifth and sixth cycle of FCR. It has been rather stupid the way the infusion center has been handling it; I've gone in three straight weeks, been hooked up to the IV line, and then they draw blood, find out my counts are too low, then they apologize all over the past and are sad my counts are horribly low, etc., then I change plans and go into work. I should have gone in the day before, had a blood draw, then they could have called me

I go to the infusion center prepared with a giant bottle of Gatorade (2 liter), partially frozen to stay cool all day, a few of my 'Issac Asimov's Science Fiction Magazine', which I have been buying in bulk from e-bay. It's a lot cheaper than to buy the latest versions, so I save money. It's also interesting to read a magazine from the 1980s, when Reagan was still president, Islamic terror attacks weren't a problem, gas was $1.25 a gallon, when Asimov was alive, when I didn't have cancer....

The stories are timeless, though. There are some topical references of course (computers weren't as ubiquitious in the 80s, there was no internet, 'green' meant what you ate for dinner, and so on). But by and large, the stories remain quite readable and enjoyable. Asimov's is one of the primary place for future award-winning stories and authors to appear. Some are clunkers, of course, but many are enjoyable and a few outstanding.

It makes the time go by quickly and pleasantly. Sometimes my wife sneaks a treat into my backpack. This time, it was M&Ms. Thanks, Sweetie!

Getting back to the CLL... I see the local onc doc (who I guess is a hematologist, but who sees, obviously, few CLL patients) on Monday. We will discuss what to do from here. My guess is...nothing. I suppose we will track my counts for the next months, pray I don't get sick, and just soldier on until the inevitable happens.

My counts are truly terrible. My neutrophils were only 0.5 on February 2, 0.9 on the 9th, and back down to 0.6 on Wednesday the 20th. My platelets have never recovered either, but truth be told, my platelets haven't broken 100 since about 2006, when I had the high-dose methylprednisolone plus rituximab. (I was looking at some old test results I've kept, and my platelets shot up to something like 876 for one test, before settling back down to the low 100s, and then declining from there. Currently, they are in the low 70s. Everyone else besides the onc doc freaks at those numbers.

Oddly, my hemaglobin has remained decent. Below normal (what else is new) but decent. As I remember they are about 12.5 or so. Certainly no difficulties at this point in time with that.

My abdominal nodes are still there. I don't think they've changed one bit during the FCR. My other nodes have largely disappeared, which is nice. I HATE having nodes. I hate it. It's an ever-present reminder of my disease. I acquired the 11q deletion after the HDMP+R trial I as on in mid-2006. Not a pleasant thing to have. The abdominal nodes can be quite painful at times.

I have been tired, but that's something we CLLers always face. I have been trying to do a bit more exercise, since that is important for over-all health and can't hurt as I try to get my marrow to recover.

I see the CLL expert in San Diego in late March. I was supposed to have finished the six cycles by then, but obviously that's not going to happen. I want to ask about maintenance therapy. Many papers have suggested that rituximab, Campath, or Revlimid can be used to help prolong complete and partial remission. Sometimes, maintenance can even push a partial remission into a complete one. I'm not a candidate for Campath with my 'massive' abdominal nodes, and Rituxan would probably be nixed for that as well. Revlimid may be a possiblity, and since they've lowered the dose to 1/10 what they started out with, side effects have declined and tolerability has improved. This is my preference as of now.

I also am scheduled for a bone marrow biopsy in San Diego. I will pray that it comes out improved, or at least not gotten worse. It's going to be a stressful time, not only psychologically, but physically since the biopsies have gotten more and more painful as time has gone on. I hope I can get some pain medication this time!

FCR Ain't a Happening Trip Right Now

2009-02-15T17:31:00.000-08:00

I'm out of the FCR treatment now because of low counts. This is a problem for many, since fludarabine can damage the marrow. Many people don't get beyond the fourth cycle, the local onc doc says.

As memory recalls a year ago, one famous CLL doc at MD Anderson told me when I got a second opinion, 'younger' patients such as myself (now 58) don't have as rough of a time as older patients do, and I should have no problem completing the full six cycles.

I have had two different courses of therapy before, so that might account for the difficulties I'm having now.

I am going back yet again next week to see if my counts have recovered enough to have the next two cycles, but to be honest, I'm losing interest in FCR.

The problems with fludarabine are legion, and eventually they will sell the drug to clean out wheel bearings only. It's way too hard on the marrow, it is so immunosuppressive that they have to irradiate the blood they give you, for fear that the few stem cells you'd ordinarily (or potentially) get in a transfusion would start re-populating your bone marrow, giving you a bad case of mis-matched transfusion leading to all sorts of problems. That's why, though, it is a good drug to give prior to a stem cell transplant.

The various docs who have opined that FCR could cure CLL are, of course, wrong. When one looks at a survival chart, there is no plateau, no levelling off of the death spiral for CLL patients.

We must look elsewhere for potentially curative regimes. FCR ain't it

2009-01-17T18:22:00.000-08:00

I did not get in to the lumiliximab trial after all. They have enrolled only one person at UC Davis. I developed a cold or upper respiratory infection and I was booted out of the trial.

However, my CLL has gone into overdrive, with a projected doubling time of only three months. Therefore, I was offered standard FCR or rituximab plus revlimid. I was really hoping for a second enrollment in the ISF 35/Memgen trial at UC San Diego under Dr. Castro, but there has been a long delay. It is just now enrolling.

(The thing they are most excited about are the 17p del CLL patients. The results so far have been promising, and the theory that a few cycles of Memgen followed by FCR might result in decent remissions for this hard-to-treat population.)

So I'm disappointed that I didn't get into a trial, but I'm more disappointed that I did not have the option of going on the ISF-35, multiple injection trial.

FCR+L Trial

2008-09-19T20:22:00.000-07:00

A lot has happened since my last post. I've been trying to get into the FCR+L trial since May, and I finally am supposed to start on Sunday, September 22, 2008. (There is a wrinkle; I've just developed a cough, so I need to have that checked out before I start the trial).

I was notified on Thursday that I have been randomized to be in the arm of the trial that includes the lumiliximab. Lumiliximab is a CD-23 antibody. It works in a fashion like rituximab, but the CD-23 marker isn't as good of a target.

The difference is that the CD-20 marker is a transmembrane protein; it pokes part of itself outside of the lymphocyte, and keeps the 'tail end' inside of the cell, in the cytoplasm I would assume. The way these markers work is they are the 'eyes and ears' of the cell, sensory organs if you will. The marker detects a signal outside of the cell in the microenvironment, and then signals inside of the cell.

Being a transmembrane molecule, the CD-2o marker is a robust one, hanging on the the cell (in large numbers, in the thousands), resisting falling off and becoming useless. The CD-23 marker, unlike the CD-20, is much more easily dislodged from the cell, and a detectable fraction of the markers are found in the microenvironment. This makes the CD-23 marker less effective at killing CLL cells.

The hope the company who is pushing this MoAB through clinical trials is that it will enhance standard therapies. Small studies have suggested that this is true; the complete remission rate with FCR+L is higher than plain old FCR.

I am scheduled to start the study this coming week at the University of California, Davis Medical Center. Although I've gotten all of my treatment so far from UC San Diego, I opted for UCD this time because the trial protocol they offered me allowed either MRIs or CT scans. Anyone who knows me knows that I dislike CT scans because of the amount of radiation, which raises the risk of secondary malignancies, a complication CLL patients are already at higher risk for.

The secondary reason is that I live in Sacramento, and this will mean not having to fly down to San Diego for follow-up visits and all six cycles, assuming I would get that far.

As far as my general health goes, I am fading, but not at a fast clip. My biggest problem is my anemia. I am in the 8.8 range at last test, and this is not normal. Even the government will pay for Epogen if the hemo rate is below 10.0, which I am.

My other numbers are terrible, but sort of holding steady. WBC at the 200,000 range, platelets (always a problem for me) at about 75, and the red blood counts, as I've mentioned, a continuing problem.

My latest test should be on my fax machine when I get home tonight, so I should know if I need a transfusion in the next day or two.

My biggest problem right now is this cough I can't get rid of. Dr. Hamblin believes I should wait before I start the trial, and I am inclined to agree with him.

I think I got this latest infection (I've been remarkably infection-free even with terrible numbers, until this year, and I've had three infections since January) from using a neti pot. This is a device that allows you to pour salt water from one nostril into the other, draining stuff and supposedly keeping you clean. However, I made the mistake of just using tap water, which is not sterile. I usually boil the water, but just forgot.

This cough has now settled into my chest. Well will see what happens.

Still Waiting

2008-08-16T10:48:00.000-07:00

I'm waiting for approval of my MRI imaging studies before I can enter the FCR+lumiliximab trial at UC Davis. The trial coordinator is Dr. Tuscano, who was nice enough to speak before the Sacramento CLL patient's group in 2006. He has been working on his own antibody, but I've not heard whether anything will come of it. It looks to be a less than rousing success, but the delays may be due to funding or other administrative problem.

So I'm in a holding pattern, in more ways than one.

One development is that I'm going down to UCSD to see either Dr. Kipps or Dr. Castro. We will see what is happening with my run-away CLL. I am less than happy with the skyrocketing counts that are not, so far, really apparent except in my large abdominal nodes. I don't feel any changes, still working full time and in the evenings seven days a week. Haven't been back in the mountains since I'm now anemic and I don't want to give myself a heart attack by hiking. Energy level has been dropping, but I'm sleeping fairly normally.

Lumiliximab is a CD23 antibody. CD23 is not expected to be a slam-bang MoAB like rituximab for the simple reason it doesn't seem to has as much killing power.

The most recent study and the reason I think Dr. Kipps has recommended this study to me is that the complete remission rate is almost 50% in previously treated patients, which is a very good result. Overall response rate is 95%.

There are two arms to the study, and you don't know what you are getting into before you sign up. You do know once the treatment is underway, so I will get at least one FCR course if I am accepted into the trial. I have more negatives (low platelets, etc.) than I did before trial number one and two. The more things wrong you have with you, the less likely they will choose you to be in their sample. They do want a success, and some folks have been accused of 'cherry-picking' patients that they think will do well for a particular trial.

It's such a game; a game with deadly consequences for the patient, at least.

2008-08-06T07:08:00.000-07:00

I saw an oncologist at UC Davis regarding the FCR+Lumiliximab trial (a word she cannot pronounce accurately). This is the same trial which was offered (recommended?) to me by Dr. Kipps. However, Dr. Hamblin calls this trial just a 'marketing scheme,' a phrase that I don't understand. I'll have to write him and ask him to explain.

I don't want to use fludarabine, of course, since it is linked to significant T cell suppression, secondary malignancies, premature death and a whole host of other problems. Once you are refractory to fludarabine (and you will become refractory), then they are no real options left for you; make sure your affairs are in order!

I was more interested in the lumiliximab trial (which is a randomized phase II trial, somewhat rare) as offered by UCD over that of UCSD, since the trial at UCD offers the option of MRIs instead of CT scans. Funny that the same company would have different protocols for different institutions. I did e-mail the company complaining that MRIs would be just as effective as CT scans at tracking the disease. The company MD who replied to me said it would be up to the trial administrator. However, the written protocol is different for the two institutions.

I'll keep this blog posted as to what happens.

CLL Rampaging Out of Control!

2008-07-31T17:01:00.000-07:00

Since my last post, all hell has broken loose, and my CLL is out of control.

My last blood test on June 19 had my WBC declining by 20k or so. I expected at least only a modest rise, if any, based on how I felt.

Wrong!

My numbers have gone sky-high, from about 30k to over 176k, in one month. I guess this qualifies as doubling in less than six months.

Thank goodness for blood tests, because I wouldn't have known I was going downhill so fast without them.

We've decided to treat as soon as possible, with something. We've decided that I should get a blood retest this week. I've been putting it off because, well, ignorance is bliss??? Isn't it???

With all the new knowledge and the prospects of better treatments in the next few years, why is this going so quickly downhill for me? That's just the way it is.

If CLL has taught me anything, it has taught me that we are all dying, some of us have it thrust in our faces every day, others only know it as an abstract thing. I used to confront this like the rest of the world, as a distant possibility; not now.

----------------------------------

We don't know if it's Richter's transformation, rapidly progressing CLL, a new cancer, or something else.

My only 'B' symptoms is that I'm tiring a bit earlier than I was a few weeks/months ago.

I'm not buying extra supplies that I might need 'someday'. That's a waste of money.

Vacation from CLL

2008-07-23T17:54:00.000-07:00

I last saw Dr. Kipps on June 19, 2008. I cancelled the July 3 appointment with Dr. Castro because it relates to the ISG-35 internode injection trial which I failed in late May. (I went from 30k to 60k in three weeks. Bummer.)

I've had several major issues with my wife. She has asthma and the hot and smoky weather in Sacramento (we always have very hot Julys, but not smoky ones) has affected her in a major way. I've shifted my focus from my CLL to her asthma.

So, the last week, I've been feeling so good I decided to cancel the July 24 appointment with Dr. Castro (also on the failed clinical trial. I thought blood work here in Sacramento would give them a picture of what is going on with me, without having to fly down to San Diego, and spending the full day down there. I hate that!

I decided I would take a slight vacation from my CLL, in a way. I thought I would take the last week and one-half, and just not think about my CLL or any other medical problems.

I got a blood draw on Monday. I'm hoping the WBC is still low, and all of the other numbers continue to be stable.

I went for a hike on Sunday and did extremely well, felt fine, and thought about doing a long hike in September or so, if I can get in appropriate condition. I was worried about anemia as I had a night of blood pounding in my ear (see Dave's blog; he found it was associated with autoimmune hemolytic anemia), but I did fine and felt wonderful. I don't think I have significant anemia, if I have any at all.

It is nice to not have to think about CLL for a week and a half.

Takin' a break

2008-07-16T20:16:00.000-07:00

I'm obviously informal since I am using an apostrophe instead of a 'g' in taking!

The weather has vastly improved. Last week was what Sacramento is famous for, hot weather! And it was hot, hot, hot! We topped out at 109 or 110, depending on where in the Sacramento region you are.

I bought a window air conditioner for the laundry room, for our semi-feral cat Mrs. Chippy. It was so terribly hot in the garage (the laundry room is the breezeway, sort of, between the garage and the house. It worked great! For $62, it was a bargain and it lowered the temperature into the 80s, a big relief from the 110 degrees it was probably in the garage. I'm going to keep the A/C there until summer is over in two months, and then put it away until next year.

On the topic: I've decided to take a break from CLL. I know that sounds odd, but I've had treatment in September, October and November 2006, and then again in May, '08. I had a partial remission from the HDMP+HDR (high dose rituximab), but relapsed quickly. I have terrible markers and no one, including me, was expecting me to last 10 years with this form of CLL. (It will be 10 years on October 1.)

My last blood numbers on June 19 showed a nice drop from my rapidly escalating WBC, and I feel pretty good, so, why not? I did see the local oncologist at UC Davis regarding the lumiliximab (randomized to 1/2 of the participants) trial. They remarked that they thought it was odd I'd be undergoing treatment when my performance level is '0' (zero, the lower number the better), working full-time, etc. So I took that as sort of a sign, maybe from God, to ignore the disease for a month. I'll have my next blood test on July 19, which is coming up fast. We will decide what to do then.

In the meantime, I am chugging away. My wife, who has severe asthma, is having trouble with our high temperatures and smoky conditions. Visibilities have been on the order of a mile or so. Terrible. You can see the smoke in the air, the sun 'sets' about 4 pm, and there is actually ash falling nearby. It has been a horrible year.

Note the sad loss of P.C., Chaya's husband, Tony Snow and others from cancer. This disease seems to take the best and the brightest, doesn't it? I don't have survivor's guilt, because I will most likely die from CLL unless something else gets me first, and it could happen in a hour, a day, or a week from now.

So, a short break from researching CLL, reading CLL blogs, thinking about the physiological nature of the disease, etc., is in order for me, and, I might add, richly deserved, at least in my opinion!

The Ups and Downs of Gene Therapy

2008-06-28T11:21:00.000-07:00

I saw Dr. Kipps on June 19, 2008. I had an excellent week the week of June 7th. I had lots of energy and got a lot done. Not quite as good this past week, but not bad.

My WBC has unexpectedly taken a turn down, which of course is good. I don't have the exact numbers, but they were up around 60,000, and have now dropped down to the 30,000 range. This is a pretty good drop. Dr. Kipps says that isn't unexpected after the gene therapy, and even after the counts have gone up the past three weeks.

To re-cap, I had the ISF35, inter-nodal injection on May 5th. I was very sick, but recovered fairly well after a couple of days, though I waited until May 12 to go back to work to be on the safe side. My counts dropped very nicely the next two weeks, but started heading upwards the third week, so I was off the trial (though there were no other treatments scheduled anyway, since this was a one-shot deal). The next appointment in early June saw my counts go up even higher. So, we started talking about FCR or FCR+lumiliximab (CD23 antibody). However, by June 19th, the counts dropped. So, there may have been a somewhat delayed action of my immune system? No one knows.

I found out that there is a FCR+L trial in Sacramento at UC Davis, through Dr. Tuscano. It would certainly be much nicer not to have to travel to San Diego and spend the money on flights and hotel rooms, instead staying here in SacTown. I did have an appointment with UC Davis on Monday, June 23 to check into the trial. I'm not sure exactly what to do right now.

I'm thinking of having another CBC (complete blood count) to see where my WBC are now. I must say that my nodes in my abdomen aren't shrinking, and this is an area of proliferation. I suppose a bone marrow biopsy would be a good idea to see what is going on as well. The danger is waiting too long for treatment; the danger is also treating if another treatment is still working, and doing something that isn't necessary right now.

However, Drs. Kipps, Castro and Weirda all think FCR or FCR+L are probably a good idea right now.

And then there is the problem with the huge radiation dose from multiple CT scans; of the neck, thorax, and abdomen. It is about 500 times the background radiation. Of course, with my probably limited lifespan, it may be that I just won't have time for a new cancer to begin. However, it still is of concern to me, if for no other reason than an MRI would be just as good.

So, we are in limbo now.

On a personal note, I noticed one of our dogs had a cyst-like lump on his side that was bleeding. This was on Thursday. We arranged for surgery yesterday, Friday. Sparky is out of surgery and doing well this Saturday. If he holds, we will bring him home tonight. Poor guy is an older gentleman of about 15. He is a funny dog who loves to be with the family.

A hot day in Sacramento, and I'm cranky

2008-06-18T23:11:00.000-07:00

I get cranky and out-of-sorts when it gets above 100. The A/C is out at work (they swear it is working (sigh) but I've attached a thin piece of paper to the vent, and this paper moves like crazy when air is coming out. The paper is dead, not moving. There is no A/C) so I've been hot all day. I got a lot of work done today, but once I got to the shop this evening, working out in the garage, it's been terrible.

I go to San Diego to see Kipps tomorrow. He's been out of town doing the presentation and hob-knobbing bit again, so he is doubling up on clinic days. I'm sure he is tired from his trip and seeing so many patients. His patient load is growing more and more, I think.

For the first time, I'm worried about my treatment. I've failed two treatments so far, and the FCR plus lumiliximab just seems dangerous to me. This is real chemo with nasty drugs that cause mutations in normal and CLL cells.

I don't have anything to base this on, but I'm usually accurate in my prognostic dreams and feelings. I'm not happy about feeling worried. But I suppose I have to do something for my growing CLL problem, and they don't have anything good to offer me. We are down to the second and third tier drugs that have major side effects.

And, Dr. Castro two weeks ago said I should be thinking of moving to a transplant. Dr. Weirda just about promised me three years of remission with FCR, but obviously UCSD doesn't think I'll last that long.

Worrisome. But we all die sometime. I'm having that lesson drummed into me like there is no tomorrow (bad choice of words?).

What Will Be My Next Step?

2008-05-29T09:30:00.000-07:00

We are weighing the merits of my next treatment. I've failed two so far, meaning my CLL cells are quite resistant to treatment.

My plan at the beginning was to use less toxic treatments with the idea that this would preserve my immune system as long as possible, and save the more powerful treatments for when I needed them. The downside to this approach is that mild treatments won't give a long remission, and meanwhile the clone is more and more unstable, leading to a complex karyotype, meaning a mixture of more and more chromosomal abnormalities, i.e. 6q del, 11q del and perhaps a mixture of even more abnormalitites.

This can make treatment more difficult.

The positive news is that I have not had any more real problems, I continue to work, I've not come down with any additional infections, and I've gotten permission at work to move to a more isolated part of the building, where I will come into contact with fewer sick people. This is one strategy I am attempting to prolong a healthy life.

I have an appointment June 6th to consider my next move. Dr. Kipps says he does not want me to get into an emergency situation with my growing abdominal nodes, perhaps requiring intervention here in Sacramento.

An update

2008-05-26T11:48:00.000-07:00

I've been getting slightly worse as time goes on :(

I finally succeeded in getting into the Ad-ISF35 gene therapy trial offered through UC San Diego. Dr. Castro is the principal investigator.

I had a rough time of it during the aftermath of the injection process. I had significant chills and vomited three times during the night and the next morning. I would recommend not eating lunch and dinner the day of the injection. According to staff, you will be sick.

My results were good for about a week! Two weeks after the trial, I noticed all of my nodes were down about 1/2, and my terrible abdominal nodes seemed to be smaller, to the point I was actually thinking of going back down a couple of waist sizes.

Unfortunately, that was not to last. At this point, three weeks after my trials and tribulations, my nodes have returned to pre-treatment levels, and I've grown a new, large node at the mid-line of my abdomen. This is proving to be very painful and troublesome. I am worried at this point about abdominal obstruction. I've been taking medication to make sure I don't get constipated.

At this point, I'm not sure what I will be doing. I am a bit worried about Richter's transformation. It is more common in patients with 11q del (me), large abdominal nodes (me) and increases with length of time with CLL (me).

I am trying a heating pad morning and evening to try to 'soften' the lymph nodes. Maybe it is helping as I don't feel quite as bad today.

What is the Incidence of Richter's?

2007-12-14T14:49:00.000-08:00

Traditional estimates of Richter's transformation range from 1% to 8%. The CLL clone can transform into an acute lymphoma, similar to a diffuse B cell lymphoma. Hodgkin's disease can also arise in CLL patients. Transformation occurs almost exclusively in the unmutated patient.

The DBCL or Hodgkin's can also arise 'de novo', which means it just pops up, and it's unrelated to the CLL cell. In other words, it doesn't transform from the CLL cells, but is a new cancer (secondary malignancy) altogether.

The latest I've read suggest that the incidence can be viewed as an increasing probability as the disease progresses over time. The rate estimated is about one percent per year in unmutated patients. That means if one lives for 10 years with CLL, there is a 10 % change the clone will transform into Richter's.

All of the amazing news coming in CLL is wonderful, but there is little progress in treating Richter's. I'm going to concentrate my charitable giving on Richter's, as the options are poor, and I'm at risk.

'Here Be Dragons'

2007-12-08T20:31:00.000-08:00

The 2007 ASH (American Society of Hematology) meeting is currently underway in Atlanta, Georgia. I am all to well aware of this since my researcher-doctor-CLL expert is in the Peach State, I suppose delivering what few items he has learned this year to the rank-and-file hematologist.

CLL remains a terrible mystery and so little is known about the disease.

If there were a map of the CLL terrain, much would be labeled, 'Here Be dragons'.

My RDC (see above) has told me, as I get sicker and sicker, that 'We have to do a better job'. Well, yeah. Since I am most likely doomed by CLL, ya think?

I told him not to be too hard on himself, since there is much blame to spread around, and, well, you know, lifting the curtain on God's mysteries is not easy work.