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Part B, Looking Back at Part A

Posted by Frederick Wasti
Aug 10 2012

Well, I've now completed five weeks (one 28-day cycle and one week of the second 28-day cycle) of Part B of my Dana-Farber clinical trial, and it seems as if I've settled into a routine. However, the Part B routine certainly seems different from that of Part A:

1. While Part A was 4 months long (actually, each "month", of course, is really a 28-day cycle), Part B will be six months long. (I will not complete Part B until mid-December.)

2. Most weeks in Part A involved only one trip to D-F (although the first week of each cycle did require three trips). In contrast, every week in Part B involves three trips to D-F.

3. In Part A, every day at D-F was a long day - lengthy infusions (especially for Ofatumumab, which alone takes about four hours to be infused) were the norm for every day we were at D-F. In Part B, only one day of each 28-day cycle (the first day) is long (because it does include an infusion of Ofatumumab), while all the other days are considerably shorter (since the principal drug used in Part B, Alemtuzumab, is given by subcutaneous injection).

4. In Part A, my blood was tested each and every day I was at D-F. In Part B, that was also true for the first cycle, but, for the remaining five cycles, my blood needs to be tested ordinarily only on the first day of each week.

In Part B, the day at D-F may start with my blood being drawn for testing (but this now is the protocol for Mondays only), and it then might take an hour to perhaps an hour and a half to get back the results so that my doctor can approve administering my medications for that week. Then (or first, if it's not a Monday), I receive as a pre-medication some Tylenol and Benadryl, and a little while has to pass (while my body absorbs the pre-meds) before I am given the injection of Alemtuzumab, which is given subcutaneously (just below the skin - i.e., not into a muscle nor into a vein) in an upper arm. Finally, I have to wait an additional hour, to make certain that there is no allergic reaction to the Alemtuzumab, and then we can head home. (Compared to Part A, which always seemed to involve either long days or very long days at D-F, most "days" in Part B are mere mornings.)

Only one day of each 28-day cycle in Part B involves a lengthy stay at D-F, and that's the first day of each cycle. On such a day, my blood is tested, then (when my doctor has seen the results) I am approved for doses of Alemtuzumab and Ofatumumab. Before either is given, however, I have to be given Tylenol, Benadryl, and an infusion of a little Methylprednisolone, as pre-meds. Therefore, the first Monday of each cycle is indeed still somewhat involved.

There is not just a difference in routine between Part A and Part B, however. Simplifying a bit, Part A used frequent doses of Ofatumumab and periodic high doses of Methylprednisolone to greatly reduce the lymphocytes in my blood and lymphatic system (i.e., my spleen and lymph nodes), and to more modestly improve my bone marrow. Part B, which uses frequent doses of Alemtuzumab and occasional doses of Ofatumumab, represents a shift in focus, since it concentrates mostly on the marrow, secondarily (but still significantly) impacting the blood and lymphatic system.

Looking at my total white cells since the start of my clinical trial...

...it is clear that Part A successfully lowered the total leukocytes in my blood from almost 60,000 (per cubic deciliter) to roughly 5,000 or so (which is actually in the "low normal" range). This is only part of the story, however, since it only shows what happened in my blood. What it does not show (at least directly) is that the situation in my lymphatic system also improved dramatically, and that the situation in my bone marrow improved significantly:

1. CT scans taken before and after Part A showed that my spleen shrank from an enlarged state (full of leukemic lymphocytes and their supporting cells) to normal size, and that nearly all of my enlarged lymph nodes (also full of leukemic lymphocytes and supporting cells) similarly shrank to normal size.

2. Bone marrow biopsies taken before and after Part A showed that my bone marrow leukemia involvement had improved as well. While approximately 35% of my marrow was involved in cranking out lymphocytes before Part A began, only about 5% to 10% of my marrow was doing so at the end of Part A.

3. Furthermore, lymphocytes showing the 17p deletion made up about 83% (10 out of 12) of the bone marrow cells tested before Part A began, while only about 25% (only 5 out of 20) of the cells tested consisted of 17p-deleted cells at the end of Part A.

In addition, during Part A, the proportion of lymphocytes and neutrophils in the blood changed dramatically: At the start of Part A, lymphocytes made up well over 80% of my leukocytes, while the percentage of neutrophils measured only in the low single numbers (far too few). Toward the end of Part A, however, lymphocytes generally made up less than 40% of my leukocytes, and neutrophils had increased to generally over 50% of my leukocytes.

But, while Part A did greatly change the proportion of lymphocytes and neutrophils in my blood, Part B has already brought about immediate and dramatic changes of its own: Looking at the proportion of lymphocytes (the red curve) and neutrophils (the blue curve) since the beginning of Part A...

...it can be seen that Part A did more or less reverse their proportions, but that Part B immediately turned Part A's reversal into an extreme - just as soon as Part B started, the neutrophils shot up into the 90% range and kept on climbing, while the lymphocytes plummeted to close to zero and have remained there since.

It is difficult to judge simply from the above graph whether it was an increase in neutrophils or a decrease in lymphocytes, or both, that brought about such a proportional change, but we can judge this quite easily by looking at how the absolute numbers of neutrophils and lymphocytes have changed over time.

First, here's how my neutrophils have changed during the clinical trial...

...and here's how my lymphocytes have changed...

Despite the fact that the neutrophil graph is pretty "wiggly", it can be seen that the neutrophils have been on an overall modest but beneficial increase during my treatment, both in Part A and in Part B. On the other hand, it can be seen from the lymphocyte graph that my lymphocytes have dropped from almost 50 (per cubic deciliter) to low single digits in Part A, and that they dropped even further (close to zero, it almost seems in the graph) during Part B. (Near the end of Part A, the actual lymphocytes numbers were generally about 2,000, plus or minus, but, once Part B began, the lymphocytes have been reduced further, to only a few dozen or so on average.)

The main points from the above data, in regards to a comparison of Part A and Part B, are that neutrophils have been able to slowly bounce back (to normal levels) during both Part A and Part B, while lymphocytes have been decimated during the same time, greatly so in Part A, but even more so in Part B.

Finally, as I pointed out further above in this post, CT scan and bone marrow biopsy results from Part A show significant positive changes to my lymph nodes, spleen, and bone marrow. However, we will have to wait for future bone marrow biopsies to see just how Part B has affected my marrow, which, don't forget, is supposed to be where Part B is targeted. Please stay tuned...

Categories: Leukemia