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Porridge

Posted by Frederick Wasti
Nov 30 2012

This week (on Monday) I started Part C of my clinical trial. The most obvious transition has been in scheduling -- unlike Part B, where we had to go to Dana-Farber in Boston three days each week, for each and every week of the past five months, we now have to go to D-F only once every two weeks. The difference between those two schedules is huge.

In Part C, I am supposedly now in a "maintenance" mode (or, at least, that is the hope). I am still receiving the same two monoclonal antibodies, at the same dosages, that I was given during Part B, but I am just receiving them much less often.

In Part C, I will be given Alemtuzumab each time I "visit" D-F, which means I will receive it (by injection) only once every two weeks, which contrasts sharply with Part B, where I was given Alemtuzumab three times per week, every week. Similarly, in Part C, I will be given Ofatumumab (by infusion) only once every two months, which contrasts with Part B, where I was given Ofatumumab once each month. (This further contrasts with Part A, where I received Ofatumumab once every week.)

Basically, Part A used Ofatumumab and high-dose Methylprednisolone to chase CLL B-lymphocytes (and, unfortunately, healthy B-lymphocytes, too) out of the lymph nodes and spleen, where they are harder to kill, and into the blood stream, where they can be more effectively attacked. The strategy in Part B was to concentrate on killing B-lymphocytes "at the source", in the bone marrow (with, unfortunately, even greater "collateral damage", since Alemtuzumab kills not only healthy and leukemic B-lymphocytes, it also kills T-lymphocytes as well).

The idea behind the "reduced" intensity maintenance protocol in Part C is this: Now that my CLL has been greatly reduced, to such a low level that it is difficult to find evidence of it, I will continue to use the same antibodies against it, and at the same dosages, but I will do so much less frequently.

I've been "beaten up" every week since last March with a fairly intense series of chemicals being "poured" into my body, but the chemicals ~have~ done their job, reducing my CLL to a very low level. To continue to beat me up further at this point would not make any sense: First, I don't think my body would be happy with taking much more of the level of medication it has been getting in either Part A or Part B. And, second, since my CLL has now been reduced to an almost undetectable level, it would also be difficult to demonstrate that continuing intense treatment was even doing any good at all.

Officially, Part B was supposed to last for six months. However, for me it lasted "only" five months. The good news is that my CLL was reduced to an almost undetectable level about a month early, and so the decision for me to be graduated to Part C likely involved the thinking that it would be difficult to justify continuing an "extra" month of abuse when it could not even be shown that it was actually doing anything productive.

However, simply stopping treatment altogether would not be a good strategy, either. Although the level of my CLL is indeed very low right now, it is ~not~ zero -- there is no simple "cure" for CLL. There are still zillions of leukemic B-lymphocytes in my body, ready to grow back in number if/when they are given the chance, and they might do so more rapidly than anyone would want -- because of the 17p deletion in my CLL cells, they have lost the normal ability to undergo apoptosis (i.e., "natural cell death"), which is to say that they just don't know how to die on their own.

In a way, Part C's protocol reminds me a bit of "Goldilocks and the Three Bears" -- Goldilocks didn't want to eat porridge that was too hot or too cold - she ate up only the bowl of porridge that was "just right" (probably while sitting on the chair that was neither too hard nor too soft but "just right", etc.). Well, hopefully Part C will be "just right" for me right now -- I will be receiving the same (obviously effective) monoclonal antibodies that clobbered my CLL in Parts A and B, but much less often, hopefully still frequently enough to keep my CLL in check, but also seldom enough to allow my body to heal and return to the vicinity of normalcy.

So, that's the plan for now -- just grin and "bear" it... (<grin>)

Categories: Leukemia

Transitions (#2)

Posted by Frederick Wasti
Nov 19 2012

During my "usual Part B Alemtuzumab Monday" at Dana-Farber today, Diane and I received the verbal news that I am likely to be graduated from Part B to Part C, effective next Monday, 11/26/2012, and I would do so one month early (i.e., in "only" five months instead of the full six months of Part B). The official OK would still have to come from Dr. Jennifer Brown, the principal investigator for the clinical trial in which I am a participant, and she would have to look at the data from my latest bone marrow biopsy to see if I made the grade. Well, this afternoon, after returning from Boston, I received an email from Karen Francoeur, my protocol nurse, that said:

"You are officially graduated from Part B to C as of Monday! Congrats!! We are working on a follow-up appt with Dr. Ho for you as well. Have a very Happy Thanksgiving!!"

1. So, Dr. Brown ~did~ give me the official OK. :-)

2. Dr. Vincent Ho would be my stem cell transplant doctor, if I did elect to transition from Part C to a stem cell transplant (a.k.a. a bone marrow transplant), and Diane and I are to meet with him once again to further discuss the possibility of such a transplant.

3. It will be a Happy Thanksgiving indeed. Never again (with the possible exception of a 100% successful stem cell transplant) would my CLL ever be at as low a level as it is right now. [Part C, which is a "maintenance" protocol, and which can last as long as about two years (actually twenty-six 4-week cycles), is intended to try to keep my CLL as low as it is right now.]

I will have more to say about this important transition soon, in upcoming posts, but I did want to get this news out as soon as possible.

 

Categories: Leukemia

Transitions (#1)

Posted by Frederick Wasti
Nov 11 2012

It seems as if I am going through some transitions as of late. Now change can be good, but it's not always so - however, I guess that at least most of the transitions described in this post are positive. So, let's take a look at some these changes, starting with some of the better ones:

At the half-way point in Part B (specifically 9/28/2012), I had another scheduled "staging day". (A staging day is a day at Dana-Farber where I have a CT scan of my entire torso and a bone marrow biopsy extracted from a hip bone, both of which provide a lot of detail on what's going on in my body, certainly more than just what blood tests can do.)

The good news from the CT scan is that my lymph nodes are mostly pretty normal (the radiologist refers to "normal" things as "unremarkable" - <grin>). The spleen measured a bit more than normal in size, but, when I asked Dr. Fisher about that, he checked with the radiologist who read this CT scan, who said:

"Depending on how we measure, the spleen is 13-16 cm(cranio caudal or anterior posterior) in size and is unchanged on all the 3 studies. It is one of the spleens which is difficult to measure consistently by different radiologists, because of the lobular margins."

So, I guess my varying CT scan spleen sizes may be due more to the fact that the radiologists are ~estimating~ my spleen rather than precisely measuring it. (?) In any event, Dr. Fisher feels that my spleen, while a little larger than normal, may be "normal" for me - after all, I'm a bit larger than average, right?

As for the bone marrow biopsy results, they are also good, at least better than in my previous two biopsies (from 3/14/2012 and 7/6/2012).

In the first biopsy, 62% of the cells counted were lymphocytes, while, in the second biopsy, the proportion of lymphocytes was reduced to 12% (but "focally higher", which I am assuming means that there were some clusters of lymphocytes here and there). In the third biopsy, there were only "scattered" lymphocytes, making up 12% of the cells counted.

The above results are "basic" pieces of information that can be obtained from a bone marrow biopsy fairly easily. However, a more sophisticated test involves what is known as "karyotyping", where the pathologist tries to find at least a few cells undergoing cell division (a.k.a. "mitosis") that happen to be at the "metaphase" stage, where the chromosomes can be seen most clearly. (There are four stages in mitosis - prophase, metaphase, anaphase, and telophase - and there is also an interphase, which is the stage between cell divisions.)

So, as for the proportion of 17p-deleted lymphocyte cells (and, in my case, it is the 17p-deleted cells that are the leukemic ones - the non-deleted cells would be normal lymphocytes), this has also improved over time. In the first biopsy, fully 83% (10 out of 12 cells karyotyped) were 17p-deleted. In the second biopsy, only 25% (5 out of 20 cells) were 17-p deleted. And, in the third biopsy, only 10% (1 of 10 cells) were 17p-deleted. (Of course, these are really only rough approximations of the actual percentages present in the marrow, based upon a very small number of cells actually karyotyped, but the trend surely does seem to be going in the right direction.)

Now, theoretically, I would have yet another staging day at the official end of Part B, which would be in December, shortly before Christmas. However, as it turns out, I actually had a staging day just this past Friday (11/9/2012), to see if I qualify to be graduated from Part B to Part C. I don't have any results from Friday's CT scan or bone marrow biopsy yet, however - I should hear about the CT scan results probably tomorrow (Monday, 11/12/2012), while the various biopsy results will become available in installments over the next couple of weeks or so. Hopefully all of Friday's test results will show continued improvements.

What we all are hoping is that I will be able to achieve "MRD status". The term MRD (for "minimal residual disease") is usually used to describe the state at which a disease such as leukemia has been reduced to a level at which it doesn't appear in "normal" testing (such as in simple blood tests), and is present at such a low level that only very sensitive tests can detect it. (Inasmuch as there is no actual chemotherapy ~cure~ for CLL, the goal of treatment - realistically - is to reduce the disease as much as is possible, to hopefully provide as long a remission as possible.)

After Part B (whether I finish Part B within weeks, or shortly before Christmas) will come Part C, which is officially for "maintenance" according to my clinical trial protocol. I can stay on Part C (which is similar to Part B, except that it is stretched out over time, where I would have to appear at D-F for treatment only once every other week) for twenty six 28-day cycles (i.e., basically for two years), or I could instead start Part C with the intent to transition to a stem cell transplant (a decision I'm not looking forward to). Much still to think about...

There is some good news to report on my rashes. I previously described a couple of rashes that I had developed beginning a few weeks ago. One of them, a seborrheic dermatitis rash on my face did respond pretty well to treatment (two topically applied creams, one an antifungal - Econazole - and the other a steroid - Desonide), although it did take quite a few days of smearing goop on my face, ears, and neck, before the seb-derm finally seemed to go away.

I have also previously described a separate hives-like body rash that I had developed on my torso and limbs. Although it was treated at first as a possible fungus infection, it was soon decided that it might actually be an allergic reaction to one of the drugs I have been taking. If the rash were found to be due to one of the Part B monoclonal antibodies (either Ofatumumab, which I had also taken earlier during Part A, or, more likely, Alemtuzumab, which I have been taking only during Part B), I would then have to stop Part B, since a "grade 3" rash (as it was judged), if due to one of the study drugs, would be reason for terminating the trial - or at least Part B - according to the protocol. [I honestly am unclear whether, at that point, the clinical trial would have been over for me, if it were due to either of the Part B study drugs (which happen to also be used in Part C), or whether I could continue with Part C anyway (since the frequency at which I would be receiving the drugs would be so much lower in Part C, as compared to Part B).]

However, Dr. Fisher thought that Bactrim (the antibacterial drug I've been taking every day since the start of the trial, which is a combination of two antibacterials, Sulfamethoxazole and Trimethoprim) might be the culprit. (He said that it is entirely possible for some people to tolerate Bactrim for quite a while, before eventually and unfortunately reacting to it negatively.) So, Bactrim was deleted from my arsenal of weapons, and I then received the steroid Prednisone for sixteen days in a row, and the good news is that the rash seems to basically be gone (it is still a little visible, in that you can see a subdued, faint "hint" of it, but I am hoping that this too will soon go away).

Of course, removing Bactrim from my meds means that I then have to change to taking a different antibacterial agent. The principal alternative is a drug named Mepron (that's the trade name - the generic name is Atovaquone), which I am now taking instead of Bactrim, and which hopefully won't also bring about a nasty rash such as Bactrim seemed to. However, unlike Bactrim, which involved taking one easy pill per day, Mepron is most effective when taken as an emulsion:

So, instead of taking one pill a day, I now have to take four teaspoons (two in the morning, two in the evening) of what might pass for bright yellow finger paint. Mepron is a very viscous liquid (much like, say, Pepto-Bismol) that the manufacturer says has a citrus taste. Well, no, not really:

OK, OK, it's not the worst thing I've ever had to taste, but it's not exactly delightful, either. I now get to remind myself twice a day that it's really too bad that I developed an allergic reaction to Bactrim...

One possible positive effect of stopping the Bactrim may be a lessening of the arthritis in my fingers that had seemed to have accelerated quite a bit over the past few months. While the original thought was that the worsening of the arthritis might have been caused by one of the monoclonal antibody drugs, it may actually have been due to a reaction to Bactrim instead. In any event, it does seem as if the intensity of the arthritis has subsided somewhat as of late, although it is possible that the Prednisone taper, which I finished a week ago, may have had a lot to do with this. Well, we'll just have to see what happens, but I am hopeful (though not certain) that the arthritis in my fingers may actually be improving...

Another transition - and definitively a good one - that occurred just one week ago was when I injected myself for the very last time with the anticoagulant Fondaparinux (trade name Arixtra). You may recall that I had to start poking myself with this "blood thinner" once each day over the past six months due to my developing a pulmonary embolism (a blood clot in my right lung, probably a side effect either of CLL itself or of the treatment for it), which was discovered in a CT scan back in early May. The good news was that the embolism had been dissolved away by the time I had the next CT scan a couple of months later. The bad news was that I still had to continue the Fondaparinux injections for another four months "just to be sure" - <grin>. However, my six-month Fondaparinux sentence did come to an end just one week ago - Yay!

A couple of weeks ago, my blood tests showed a significant drop in the platelet count. Although, way back at the start of the trial, my platelet count was at about 80 (in thousands per microliter), the count rose pretty rapidly to where it was generally well above 100, averaging typically about 130 or even 140. However, a couple of weeks ago, it did drop down into the low 80's:

Now, this was not just a one-day blood test result (which simply could have been an error) - this was the result from each of two separate days that week:

However, the good news is that the platelet count did bounce back to about 125 or so last week - we'll see how it looks tomorrow, with my usual Monday blood test results. And, I should have some CT scan results tomorrow, too, I hope.

Finally, one negative transition that is taking place as of late that I will mention here is that the seb-derm rash on my face has gradually been returning again. (This is not overly surprising, since much of my immune system is currently on vacation somewhere.) So, I have had to resume my twice-daily Econazole and Desonide treatment once again. Hmmm...

Well, I would say that there have indeed been a lot of transitions lately, and there may (will?) be more to come - please do stay tuned...

Categories: Leukemia