Failing CAL-101/GS-1101?

I saw Dr. Coutre at Stanford Clinic yesterday, and was dismayed to find out my lymphocyte count has gone up to 20,000.  This is the highest it's been since I started on CAL-101, and may very well be a sign that I am failing the drug.  I think everyone knew this isn't a cure, but I also think that we all hoped I would get a number of years of remission from the drug.  A year and a half doesn't seem that long, in retrospect.

We will follow up with a WBC next month as part of my IVIg.  If there is continued increase in the lymphocyte count, then it is likely I will be pulled from the trial.  That would be a big disappointment, of course, since there is not much out there I would qualify for.  The Bruton's tyrosine kinase inhibitor unfortunately is completely filled, so there would be no room for me.  The other option would be conventional chemotherapy which does not work anymore on me.

So I may be going from a stable situation in which I feel well and am able to live a pretty much normal life to one where CLL is once again front and center.  I know I have done better than many (but not all) and I shouldn't complain, but this indeed is a real blow.

I'll try to stay on the positive side, at least for another month.

I suppose I will go back on the prayer list from my church.  Prayers do help, in my opinion.  I think they were a God-send when I was so sick in the hospital.

In, and out, of the hospital

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!

Surprising Results

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.

Things pretty much the same

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.

Alan Sullivan

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?

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

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.

Hangin' in there

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!

So how am I doing?

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

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.

Platelet Numbers Increasing

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.

Might a Major Development in CLL Treatment Be in Sight?

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

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

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.

When should I start treatment?

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

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.

"Simply Doomed to Achieve Complete Remission"

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.

Is your Health Care Practitioner Reading Your Blog?

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!!!

Cholesterol and CLL-How's it Going?

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.

Feeding the Beast

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.