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Excellent, But...

Posted by Frederick Wasti
Jun 06 2012

It was "just" a normal Ofatumumab day at the Dana-Farber Cancer Institute today - an intravenous line, blood drawing, waiting for blood tests, a couple of acetaminophens, a Benadryl, and 1000 mg of Ofatumumab. <Ho-hum...>

The only slowdown today (and it really was slight) was the manual changing of my Benadryl dose from the 50 mg that is the "normal" Benadryl dose for the clinical trial to "my" 25 mg dose (to keep me from turning into a total zombie). It seems as if the flow of electronic paperwork at D-F just doesn't want to accept 25 mg for my Benadryl dosage, because it seems as if everyone concerned, from doctor to patient, has to be involved in making this change each time. (To be clear, the infusion nurses always do know about the change, but they do have to have a doctor OK the change each time - at least until such time that the D-F medical records software will cooperate.)

One thing that was nice today was that neither the Benadryl nor the Ofatumumab seemed to have affected me as strongly as they have on other recent Wednesdays. That is to say, I was not as groggy and didn't feel as weak as "expected". It was not a huge difference, but it was gratifying.

Blood test results also had some excellent news. The total white cell count continued on its downward course:

Having a total lymphocyte count of 6.9 (in thousands of cells per microliter) is not only within the normal range, it is actually below the middle of the normal range (which is approximately 5 to 10). In fact, looking at my historical total lymphocyte counts...

...it can be seen that my latest WBC count is as low as it has been since before 2005. This is primarily due to the clinical trial decimating my lymphocytes, which have been mostly leukemic lymphocytes,...

...but, unfortunately, the non-leukemic lymphocytes, and other white cells as well, have been affected, too.

The process of internalizing all of the above produces a mixture of emotions: There is exhilaration over seeing white cells now within the normal range, but there is also the increasingly obvious realization that the majority of those lymphocytes are still cancerous cells, and they will, when given the chance (when the clinical trial is eventually over) start growing back again.

I have known all along that the drugs I am receiving (even if they are "state of the art") are far from perfect. After all, Ofatumumab does target ~only~ B-lymphocytes, but it targets ~all~ B-lymphocytes, whether healthy or leukemic. Methylprednisolone is even less specific, since it affects white cells in general, and not just lymphocytes. And, during Part B, I will be receiving injections of Alemtuzumab, which targets both B-lymphocytes (including my leukemic B-lymphocytes, but the normal B-lymphocytes, too) as well as the less common but also very important T-lymphocytes (which are not leukemic at all).

None of these drugs is specific enough to target only leukemia cells alone. None.

So, the nagging feeling that my treatment is "succeeding" (in that my white cells have dropped well into the normal range), but is also ~not~ succeeding (in that I still have zillions of CLL cells in my body) is coming more to the forefront. The only way to reduce my leukemic cells further is to reduce my white cells (especially my lymphocytes) further, but obviously it would be impractical to attempt to destroy all of the leukemic cells this way.

[I should point out here that I am in this clinical trial, specifically designed for us 17p-deleted CLL people, simply because all of the above is likely true - the alternative approaches, such as the so-called "gold standard" treatment of "FCR" (Fludarabine, Cyclophosphamide, and Rituximab), would not be able to kill off my 17p-deleted CLL cells very well, and such therapies would more easily destroy normal lymphocytes than they could destroy 17p-deleted leukemic lymphocytes, resulting in a proportionate ~increase~ in CLL cells (even as the total number of lymphocytes declined during treatment).]

There is the possibility (and it is my hope that this is a ~strong~ possibility) that, once most of my lymphocytes have been flushed out of their comfy, cozy, safe hiding places in the lymph nodes and spleen (and my lymph nodes and spleen ~have~ shrunk significantly or perhaps even dramatically so far in Part A), my body will do a better job at recognizing the leukemic B-lymphocytes as being "wrong", i.e., as being "foreign" (as in "far from normal"), and that it might start attacking them more vigorously than before, back when they were in hiding. <fingers_crossed>

So, just what is the endgame?

I know I'm getting a bit afield here, but here is my view of the future, where, from this point in time, I can realistically envision two possible favorable scenarios:

1. I may have the "opportunity" of submitting to a stem cell transplant (SCT) (a.k.a. bone marrow transplant). In fact, an SCT is listed in this clinical trial's protocol as a possible option to replace Part C (which is a lower-level maintenance mode of treatment, but which is limited to 26 cycles, ending a little over two years after Part B ends). The upside of an SCT is that it does currently present the only ~possibility~ of an actual cure (and only ~if~ the SCT is actually successful, and that's still a big "if") - that is to say, with an SCT, my lymphocytes (in fact, my whole immune system) ~could~ in fact be reduced to zero, only because they would be replaced with lymphocytes (and other components of the immune system) from a generous SCT donor. But there certainly are significant possible downsides to an SCT, which I won't go into here (but which I have alluded to previously, on April 15th), making an SCT not something I am looking to jump into as soon as possible (even as it remains something that I do have to keep my mind open to nonetheless).

2. There are exciting new drugs, very different from the current generation of drugs, that are now "in the pipeline". I won't be able to go into all their details here (although I ~will~ discuss them later on), but I will state here that there are several "kinase inhibitors" (term to be explained later) that are undergoing clinical trials right now that do show great promise at ~controlling~ CLL (not curing it, because that is only possible with a successful SCT), keeping CLL in check over a hopefully long period of time. Additional pieces of good news regarding these kinase inhibitors are that side effects (as compared to "traditional" chemotherapy) seem to be more tolerable for most CLL trial patients, and that the drugs can be administered as daily oral pills. And for me, one additional characteristic of the new kinase inhibitors that is ~very~ important is that most of them seem to be "blind" to 17p deletion - that is to say that most of them cause CLL cells to undergo apoptosis from signals sent along biochemical pathways that do not rely on the presence of the 17p protein (which is not found in most of my CLL cells due to the missing TP53 gene that is absent from my damaged 17th chromosomes) - in other words, most of the new kinase inhibitors could keep my CLL under control as a chronic but low-level disease for a hopefully long period of time. However, it does take years of testing before any of these new drugs will be available commercially.

So, in my mind (and heart), I am most hoping for rapid progress with kinase inhibitor research and development, for release as soon as possible. And, I may even be able to get accepted into clinical trials using them before that time comes to pass. I just have to live long enough to be able to do so. Or, I might have to grit my teeth and start to look more seriously at an SCT instead. Or, maybe there'll be a miracle... (Uh-huh...) In the meantime, ~my~ job right now is to try to achieve the best remission possible from this clinical trial - that would make all possible good scenarios better.

Well, I ~did~ say I was going to be "getting a bit afield here"... <grin>

Categories: Leukemia