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Nearing the End of Part A

Posted by Frederick Wasti
Jun 28 2012

Yesterday (Wednesday, June 27th) was just another, pretty routine "regular Ofatumumab day" at Dana-Farber. I seem to be able to handle the Ofatumumab pretty well now, all things considered - the side effects seem to be slightly less each time, and I felt not very "beaten up" at all on the way home. So, I guess "routine" was the word for the day.

Yesterday's blood test results also seem to be a bit "routine", too, in a way. At least, they do not seem overly different from the last couple of weeks, and my previous "Bottoming Out ?" feeling seems to still be valid. Admittedly, the ~details~ of what is going on in the blood, in the lymph nodes and spleen, and - maybe especially - in the bone marrow, are all still unknown to me, and those details could be ~very~ important, but the "big picture" numbers seem to be rather stable (if that's the word for it).

Here is how the total white cell count since diagnosis looks:


It does seem that, over the last few weeks, the total leukocyte number has been hovering around 10, 000 per microliter. That is not bad news, of course - hovering around the upper limit of the normal range is a whole lot better than approaching almost 60,000 per microliter, as I was doing just a few months ago. (And, it's also a good thing that the point of starting treatment is so easy to spot on the graph.)

Looking at the percent of lymphocytes since diagnosis...

...does show that the lymphocytes are down into a normal range, keeping in mind that lymphocytes normally make up approximately 30% of the total white cells. However, I still don't know what proportion of my lymphocytes are leukemic cells.

The neutrophil percentage, which had declined since diagnosis, and which seems to have been approaching "bottoming out" before treatment started...

...now looks quite good, considering that neutrophils are supposed to make up approximately 60% of the total white cells. In other words, the neutrophil news is all favorable. And, unlike my lymphocytes (where no one at the moment knows how many are normal and how many are leukemic, and how effective they might be at detecting foreign bodies in my tissues), presumably all of my neutrophils are normal, and ready to do ~their~ job of fighting off bacterial invaders.

Part A will be ending soon. I have one more (hopefully routine) "regular Ofatumumab day" coming up next week (although it will be on Tuesday, since Wednesday will be the Fourth of July). And, on Friday I am scheduled to be back at Dana-Farber for a full day - blood tests, a CT scan, a bone marrow biopsy (BMB), and a meeting with Dr. Fisher. The CT scan results may be available to Dr. Fisher in time for us to discuss them, but the BMB results will not be fully back for a couple of weeks (although some of the results may be available sometime the following week).

Hopefully the CT scan will show that my lymph nodes and spleen, which had all seemed to have improved during the first half of Part A, will continue to be in good shape (and I honestly do expect that to be the case). The state of my bone marrow, on the other hand, is more in the realm of the unknown. It remains to be seen just how much improvement there has been over the past few weeks, and the BMB results will help clear this up. Time will tell...

Then, Part B will finally begin the following week. For Part B, I will still be receiving Ofatumumab, but only on the first day of the each of the six 28-day cycles (instead of once each week, as in Part A). The big change in Part B will be that I am to start receiving another monoclonal antibody, Alemtuzumab, given by injection, three times each and every week of each cycle for six months. I'll have more to say about this new drug pretty soon.

Categories: Leukemia

Bottoming Out ???

Posted by Frederick Wasti
Jun 21 2012

Yesterday (Wednesday, June 20th) was a "regular Ofatumumab day" for us at Dana-Farber. Things went pretty routinely, and I didn't feel too bad after the treatment yesterday afternoon and evening, and I feel quite well today. Most of the obvious effects of last week's HDMP assault seem to be past - I'm feeling ~much~ better than I felt, say, on Monday or Tuesday.

The blood tests from yesterday were mostly fairly good news. The first item I tend to look at when viewing test results is the total white cell count - it's nice to see it going down, and not so nice to see it going up - and, on yesterday, well, it did go up a bit:

However, there were some other numbers to look at, too. While the percent of lymphocytes seems to be dropping not all that much as of late...

...at least the percent of neutrophils does seem to be slowly increasing:

It seems to me as if the lymphocyte decline has now sort of "bottomed out" - that is, it does seem as if Part A has basically killed off about as many lymphocytes as it's going to be able to (and, although it is possible that it is mostly leukemic lymphocytes that are dying, and not normal lymphocytes, the opposite could also be occurring).

The above two graphs show the ~percent~ of lymphocytes and neutrophils - the next two show the ~absolute~ numbers - first, the lymphocytes...

...and then the neutrophils...

It can be seen from the above that the actual number of lymphocytes seems a bit "stubborn" about dropping much further. However, the actual number of neutrophils seems to be on a modest rise. So, I guess my "takeaway" from all the above data is that:

1. The total number of white blood cells did increase this past week.

2. However, that increase is mostly due to a beneficial increase in neutrophils.

3. Meanwhile, it seems as if the lymphocyte count (while now much, much lower than it was before treatment started) no longer seems to be changing all that much.

I have two more Wednesdays of Ofatumumab infusions to "look forward to". Then, basically that would be the end of Part A of the clinical trial. I will then have a CT scan of my innards and a bone marrow biopsy taken from my hip, both in order to show the state of my disease. Hopefully the scan will show even more shrinkage of lymph nodes (and maybe shrinkage of my pulmonary embolism, too), and the biopsy will show decreased lymphocyte involvement in my marrow. We'll see...

Then I will start Part B...

Categories: Leukemia

Methylprednisolone and Me, a Love/Hate Relationship (#2)

Posted by Frederick Wasti
Jun 19 2012

Since I have not added a post here in a few days, I have been trying for the past couple of days to update the blog with another entry, but I am still in the throes of last week's high-dose Methylprednisolone, and, besides feeling physically quite weak, I am having trouble putting any sort of logical thoughts together "on paper" (so to speak). So, about the best I can do right now is to say so, and to apologize (I am sorry). I will have more to say once again soon...

Categories: Leukemia

Final Week of Methylprednisolone (#2)

Posted by Frederick Wasti
Jun 15 2012

Just a quick update to my "Final Week of Methylprednisolone (#1)" entry from two days ago. I'm typing this while sitting in the infusion chair, but I won't upload this entry to the blog until we get back home (due to security concerns with the public-access network I'm on here at Dana-Farber - I don't mind surfing the 'net here, but I really shouldn't send password login info over a non-encrypted public network).

To help commemorate my last "installment" of HDMP today, my super infusion nurse, Melissa Houston, took the picture below with her camera phone and emailed it to me so that I could use it in this blog. (Thanks, Melissa.) (<smile>)

Good-bye, HDMP !!!

However, in a sense, the subject line of "Final Week of Methylprednisolone" is somewhat incorrect. It ~is~ true that this should be the last week that I receive HDMP - a total of 7,200 milligrams of Methylprednisolone over three days - that's over 7 ~grams~ of Methylprednisolone, totally overwhelming the mere 20 milligrams or so of Hydrocortisone that my adrenals would make in a normal day. Over seven grams of a very powerful steroid (about 5 to 7.5 times more potent than Hydrocortisone) is indeed ~HDMP~. (However, technically, the HDMP would actually be overwhelming the pituitary gland in my head, which senses corticosteroid levels in the blood to control the release - or, in this case, the non-release - of Hydrocortisone from the adrenal glands.)

However, when I was typing up that "Final Week of Methylprednisolone" entry (and, in my defense, I was already under the influence of some of the HDMP effects at the time on Wednesday evening - <grin>), I had forgotten that I would still occasionally receive "LDMP" (i.e., "low-dose Methylprednisolone" - that's "only" 50 milligrams) as "preconditioning" on those days that I would still be receiving infusions of Ofatumumab. However, there's a long way from 50 milligrams to 2,410 milligrams (which is what I received on each of the three D-F days this week).

Next week we will be at D-F just on Wednesday, for Ofatumumab (after some "LDMP preconditioning")...

Categories: Leukemia

Final Week of Methylprednisolone (#1)

Posted by Frederick Wasti
Jun 13 2012

Today was the first of three days of my final week of Methylprednisolone at Dana-Farber. You may recall that the four 28-day cycles of Part A of the clinical trial involved receiving Ofatumumab every Wednesday, and HDMP (high-dose Methylprednisolone) for three days (Wednesday, Thursday, and Friday) of each first week of each 28-day cycle. Well, today, tomorrow, and Friday are the three days of Cycle 4 of Part A, so these are the last three days for Methylprednisolone (or maybe four, or seven, or seventeen - the effects of Methylprednisolone last for many, many days after the infusions stop...).

[Looking ahead to the six 28-day cycles of Part B, I will no longer be receiving Methylprednisolone at all, and instead will be receiving less frequent (once per cycle) infusions of Ofatumumab, but quite frequent (three times per week) subcutaneous injections of Alemtuzumab).]

Today was not just a normal "first day of the cycle", however. The first inkling that it might be different occurred last night, when we received a phone call from D-F Scheduling, to learn that our 7:30 start was to be changed to 9:00. (No reason was given, and no reason was asked for.) Today we found out that D-F had run out of Ofatumumab, but would obtain some this morning for me. The D-F Pharmacy Department said "by 10:00". My nurse practitioner (who gave me a physical exam first thing this morning) said "maybe by 11:00". Melissa Houston, my superb infusion nurse, said, "well, maybe by 12:00". Well, some Ofatumumab did arrive from Mass General Hospital a bit after 12:00, but then we had to wait a little longer because the D-F Pharmacy Department had to prepare my dose of it. So, I guess today's infusions probably started some time after 12:30.

Obviously, with such a late start, everything got backed up quite a bit, since I had to take an infusion of HDMP (after the acetaminophen and Benadryl pills), and then an infusion of Ofatumumab (and the latter infusion, just by itself, takes about four hours). The bottom line is that we didn't get away from D-F today until about 6:30.

However, since the day was longer than usual, but did not cost us any more, I guess "we got ~more~ for our money" this time - <grin>.

As for the blood test results, the total white cell count, and both the absolute counts and relative proportions of both lymphocytes and neutrophils, were all about the same as last week. (Actually, they were very slightly worse, but the differences seem insignificant - "nothin' ta worry 'bout".):

However, I've also been watching the platelet counts over the last few months, too, since platelets are important for proper clotting of blood, and are often impacted by CLL:

The good news shown here is that, while it does seem as if the platelet count does certainly fluctuate a lot from test to test, the overall trend, while downhill before starting treatment, has now been heading uphill ever since. A platelet count of less than, say, 100, is not only important because it can result in poor clotting ability, but is also an indicator that rampant CLL growth may be crowding out platelet production in the bone marrow. So, the above platelet trend is indeed gratifying.

[Of course, despite any previous possible loss in clotting ability, I did have just "one clot too many" during this time period, resulting in my "surprise" pulmonary embolism, for which I am still "merrily" injecting myself with Fondaparinux each morning - <grin>.]

Well, we're off to D-F for tomorrow and Friday mornings, for the final two days of HDMP. YAY !!!

Categories: Leukemia

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