Liver numbers have gone down on CAL-101

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.

An update

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.

An update

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.