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

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

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

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

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

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

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

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.