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Home for the Holidays (well, sort of...)

Posted by Frederick Wasti
Dec 31 2012

Well, I developed pneumonia and ended up in Brigham and Women's Hospital (BWH) in Boston (on Sunday, 12/23), and I spent about a week there before I was discharged (yesterday, 12/30). It is ~great~ to be home.

As for "Home for the Holidays", well, it was a one-out-of-two situation - I did indeed spend Christmas away from home, but, early last week, one of the BWH doctors stated that he was hopeful I'd be home before New Year's, and here I am, at home, on the morning of New Year's Eve, and that's a good thing, right?. (<smile>)

If I were asked whether my Holidays, therefore, were a glass-half-full or a glass-half-empty, I would answer that my glass was actually quite full. Not only did I have visitors in the hospital for Christmas (so, it isn't as if I had been alone), I also had the chance to win another epic battle against millions of the microbes that each and every day try to bring down each and every one of us. And, I'm home in time for New Year's. So, when all is said and done, what's not to like? (<smile>)

I will have more to say about a few of the more important (to me, anyway) aspects of my stay in Boston later, but I just wanted to post this today.

And I'd like to wish everyone a Happy (and Healthy) New Year !!!

Categories: Leukemia

Campath (#1)

Posted by Frederick Wasti
Dec 13 2012

I would like to devote this post to Campath, the monoclonal antibody that I first started taking during Part B of my clinical trial. If the name seems new to you, it probably is because I have usually referred to it throughout Part B, and now into Part C, using its generic name of Alemtuzumab. Now, that will likely sound more familiar to you - <smile>. (I actually have used the brand name of Campath a few times, but usually only just parenthetically.)

I should point out that it seems as if I always have to be familiar with at least two names for every drug -- there is generally a trade name (or two) and there is also a generic name for each drug, and often both names are quite commonly used. For example, especially in Part A, I received high doses of the steroid Methylprednisolone (with occasional lower doses in Parts B and C), and at D-F it is sometimes called just that (which is its generic name), or maybe "Methylpred" for short,...

...but sometimes it might also be called Solu-Medrol, or Su-Medrol, which are two of several trade names for it...

 

Similarly, the first clinical trial monoclonal antibody I received is most often referred to generically as Ofatumumab, but it might also be referred to at D-F simply with the nickname of "Ofa", or as Arzerra, which is its trade name.

Well, at D-F, Alemtuzumab is most often referred to as Campath (which is certainly easier and quicker to say). However, when a syringe full of Campath arrives at my infusion chair for injection into me, the label will say "Alemtuzumab" on it (and it will not say "Campath"), and my infusion nurse and a second infusion nurse (and at D-F ~two~ nurses are always required to check such a drug before it can be administered) will both check it for its identity and its quantity (and my identity, too, but fortunately not my quantity - <grin>) using the name of "Alemtuzumab" - they will read "Alemtuzumab" on the syringe label, they will read "Alemtuzumab" on the paperwork that they both have to sign, and they will say "Alemtuzumab" out loud when confirming to each other just what I am about to receive. Still, at most other times, the D-F personnel will use the "easier" name of Campath.

Campath has a history that goes "way back" to 1979, when it was first synthesized by Herman Waldmann while working in the Pathology Department of Cambridge University in the UK. (At this point, you may have just figured out why Campath is called "Campath" - it was a product of CAMbridge University's PATHology Department - <smile>.) Now, you might be thinking that 1979 is not exactly "way back" in history at all, but, in the history of the development of monoclonal antibodies, it really is -- in 1979, experimental work with developing MABs (as monoclonal antibodies are often called for short) was indeed still in its infancy.

What Campath does that makes it useful for treating CLL patients (especially those of us with a 17p deletion in their CLL cells) is that it kills leukemic (and, unfortunately, also normal) B-lymphocytes (but is not dependent on having unmutated #17 chromosomes to do so, unlike most other anti-CLL agents). Campath attaches itself to the CD52 protein antigens on the surface of lymphocytes, and, when it does so, this ends up starting a process that destroys such cells. (If you're a bit vague on the significance of the CD molecules on the surface of blood cells, you might check out my previous blog entry on "How Monoclonal Antibodies Work" from 9/2/2012.)

You may remember from earlier blog entries that Ofatumumab and its more frequently used competitor, Rituximab (trade name Rituxan), kill B-lymphocytes similarly (although not identically), but they attach themselves to CD-20 molecules, instead of CD-52 molecules. But, since CD-20 molecules are found only on B-lymphocytes, and since CD-52 molecules are found on both B-lymphocytes and T-lymphocytes, Ofatumumab and Rituximab will kill only B-lymphocytes, which are involved in CLL, but Campath will kill both B-lymphocytes and T-lymphocytes, even though T-lymphocytes are not involved in CLL at all, so it turns out that Campath does cause greater "collateral damage". However, Campath does a remarkable job of killing B-lymphocytes in the bone marrow, which is something most other anti-CLL MABs are not quite as good at - the CD-20 MABs tend to work well in the bloodstream and to some extent in the lymph nodes and spleen, but not quite as well in the marrow, which is where Campath really shines.

Just for an example of the power of Campath at destroying lymphocytes, let's take a quick look at how the absolute number of lymphocytes in my blood have declined during my clinical trial:

Notice that, during Part A, my lymphocytes dropped gradually from almost 50,000 per cubic microliter down to about 2,000 per microliter, but, immediately after Part B started, just two days later, they had dropped from 2,000 to only about 40 lonely lymphocytes per microliter. Because of the scale of the graph, this difference may not be totally apparent, but, let's take a look at how the percentage of my white cells that were lymphocytes varied during the trial:

Here, even if I hadn't labeled the "Start of Part B" (which is when I first began receiving Campath), I'll bet you could probably guess as to where it is on the graph. In just two days, my lymphocytes plummeted dramatically, from about 35% of my total white blood cells to only about 1% of my white cells, and the percentage has remained in the vicinity of 1% ever since. Such is the power of Campath.

Interestingly, though, it was the fact that Campath destroys T-lymphocytes (in addition to B-lymphocytes) that caused it to be first tried as an aid during bone marrow transplants in 1982. It was known, even at that time, that transplants too often failed due to the recipient's T-lymphocytes' proclivity to attacking the donor's cells, so Campath was tested in a very small number of cases to see if its depletion of T-lymphocytes would help prevent rejection, but the results of these experiments were mixed.

However, starting in 1985, Campath was also tried on very small numbers of CLL and Non-Hodgkins Lymphoma (NHL) patients and, although the results were also mixed, they did appear more promising than the results from the transplant experiments (and more so for CLL than for NHL). Shortly after the CLL experiments had started, Campath was also tried with some success on several different auto-immune diseases that involved T-lymphocytes, and with some success, although one of the disappointments was that patients with Rheumatoid Arthritis (RA, an auto-immune disease, quite unlike the more common osteoarthritis that I have) did not respond very well overall.

In the early 1990's, there were some interesting experiments run on a number of persons having Multiple Sclerosis (MS) that did provide some encouraging results, and even some of the failures provided researchers with new insights into just what may cause MS to progress. However, I will have more to say about the use of Campath in treating MS and CLL in the next blog entry - so please stay tuned...

Categories: Leukemia

W&W Once Again (#2)

Posted by Frederick Wasti
Dec 11 2012

Well, yesterday was a treatment day at Dana-Farber. The schedule was pretty typical for how most of the Part C days should be (and, in fact, it would be typical for how many of the Part B days had been as well), where I have blood drawn for testing, and later (after the blood test results are back) I have an injection of Alemtuzumab and an examination by Michele Walsh, my D-F nurse practitioner. (On the other hand, once a month in Part B, and once every two months in Part C, the treatment day is longer and more involved because of a long Ofatumumab infusion and addition pre-meds.) I did feel somewhat "treated" later on at home yesterday, but I felt pretty good by the evening. "A piece of cake"...

My main focus for yesterday, though, was on seeing my blood test results, which would be the first results showing any changes (if any) that might be occurring as a result of the reduced (i.e., stretched out) Part C schedule of being treated only once every other week. My concern, of course, is that the counts might have shifted somewhat, specifically showing more lymphocytes perhaps.

Well, the ~good~ news is that the blood test results were once again rather "boring" (<smile>). For the 100 white cells counted this time, 99 were neutrophils and (still) only one was a lymphocyte (and the 100 did not include any monocyte this particular time). After doing all of the advanced math necessarily involved, I can now say that I have 99% neutrophils and 1% lymphocytes.

So, the results from yesterday were basically the same as they have been for a number of months (since shortly after Part B began) - typically only about 1% lymphocytes, with the rest being all or almost all neutrophils, with an occasional monocyte showing up (or, on rare occasions, perhaps even an eosinophil). So, there is no significant change in my differential white cell count from my peripheral blood, but, of course, I don't know yet what could possibly be changing in the bone marrow and/or in the lymph nodes and spleen (but hopefully no changes are happening in those places as well).

Of course, it is worth remembering that these percentages are still quite unbalanced. Ordinarily, neutrophils are supposed to make up 49% to 79% of the white blood cells (and not as much as 98% or 99%), and lymphocytes are supposed to make up as much as 11% to 38% of the white cells (and certainly not just 1% or so). Of course, these numbers (and I took the normal range numbers from a D-F lab results printout) show the relative proportion of the white blood cells and not the actual numbers. The absolute number of neutrophils is now pretty close to normal (perhaps "high normal") -- it is the scarcity of lymphocytes that makes the percentages so lopsided.

However, today I would also like to take a look at my red blood cells and my platelets for a change. With leukemia, it is the white cells that, not surprisingly, get the most attention, but red cells and platelets can be negatively impacted by leukemic cells crowding out other cells in the marrow, and/or they can be negatively impacted by the treatment regimen used to reduce those leukemic cells (but also causing "collateral damage").

For my red blood cells, there really does not seem to have been too much of an impact because of CLL or because of treatment. Looking at my red cell counts during the trial (and I have added upper and lower normal limit lines for the "official" D-F range of 4.2 to 5.6 millions of cells per microliter),...

...it can be seen that my red cells have been a bit on the low side during treatment (and, in fact, dipped a bit more during the summer, probably while the Alemtuzumab was busy "beating up" my marrow), but, if we look at my red cell counts historically (from as far back as I have records),...

...it is clear that I have always (or, at least for a long time) had "low normal" red cell counts (although, admittedly, the CLL and/or the treatment for it, may have lowered the counts a bit more). However, I don't really think too much about the red cell counts - i.e., they're basically OK, or, at least, "good 'nuf".

On the other hand, the platelet counts have been more of a concern throughout the trial. In truth, they are too low, as a graph of my platelet count during treatment will show:

However, while they are low (and below the normal range most of the time over the last few months), my platelet counts are not quite at a dangerous level, where I would have to be treated for a too-low platelet count and/or have to suspend my CLL treatment for a while to allow them to recover somewhat. (Michele Walsh, when we were discussing my platelet counts yesterday, mentioned that Alemtuzumab is rough on platelets, and, in fact, some patients have had to suspend treatment for a while simply because of that, but that my platelet counts have been "high" enough that doing so has not been necessary in my case).

Actually, looking at historical data, my platelet counts, like the red cell counts, have always (or, at least for some time now) been at a "low normal" level:

Hopefully, in Part C, having treatments much less frequently, perhaps my red cells and my platelets can improve somewhat. What I need is just enough treatment to keep my CLL in check, without too negatively impacting red cell and platelet production in the bone marrow. Too much treatment would hurt the production of many types of cells in the marrow, but, if the CLL were to return, that would also hurt such production, as the leukemic lymphocytes crowded out other cells there, so it's a balancing act, I guess.

I'll be watching and waiting...

Categories: Leukemia

W&W Once Again (#1)

Posted by Frederick Wasti
Dec 09 2012

When people are diagnosed with CLL for the first time, it is unusual for them to need or receive immediate treatment, and, in general, CLL patients upon diagnosis generally begin a period of months or even years (depending on how fast their disease progresses) of "watchful waiting" (or "watching and waiting") (or perhaps "watching and worrying") before they finally start treatment. (Statistically, it has been shown that prompt treatment for CLL is not helpful, and, due to the side-effects of the treatment, it may do more harm than good in the long run, so the first "treatment" for nearly all CLL patients is "no treatment".) In my case, I was in W&W status from September of 2010 until March of 2012 - about a year and a half - before I started treatment at Dana-Farber.

Now, however, I seem to find myself back in W&W status once again. Oh, it's different, in that I am still being treated once every other week, but the big question on my mind at the moment is what will happen to the state of my CLL during the Part C "maintenance" period. Will it stay very low, or will it start coming back, and, if so, will it grow slowly, or will it grow rapidly? So, in other words, I'm back to "watching and waiting" once again...

At the moment, in Part C, my blood is to be tested every other week (on those days that I go to D-F for treatment), and I will be looking forward to seeing each new set of test results with increased anxiety. (And, I assume that I will still have occasional periodic bone marrow biopsies and CT scans, too.) In between, though, it's W&W time. So, while watching, and while waiting, I would just like to take a look at my blood counts as they are right now (well, from almost two weeks ago, the last time my blood was tested), to see where I stand, at least for my white blood cell counts, after being graduated from Part B to Part C. And then, tomorrow, I will be back at D-F once again, for treatment and for some more blood testing.

So, on to the graphs...

If one were to look at just my total white cell counts, it is clear that I had far too many white blood cells before treatment began, but, since the summer, my leukocytes have been basically within the "normal" range -- I have added a couple of green lines to show the approximate proper lower and upper "limits" of white cells (which are "officially" given as 3.8 and 9.2, in thousands of cells per microliter, on my D-F lab printouts), and you can observe that I have been within or at least close to the "proper" range for quite a few months now.

Looking back even further, using data from the last decade or so, it is clear that my leukocytes have been too numerous for some time now, even though it was not all that many years ago that I did have normal white cell numbers...

Of course, the total leukocyte count is only part of the story. Since the various types of leukemia involve only certain types of white cells, we have to take a look at what ~differential~ white blood cell counts show. In my case, with Chronic Lymphocytic Leukemia, it should be obvious that it is the state of my ~lymphocytes~ that is important, right?

Taking a look at the absolute number of lymphocytes since my clinical trial began (with added lines for the "official" lower and upper limits for the normal range of 0.5 to 2.6 thousands of cells per microliter),...

...it is clear that I was significantly above the normal range when treatment began, but then rapidly declined during Part A, and then basically "bottomed out" at the beginning of Part B. Going back further, to the time of diagnosis,...

...it is evident that my lymphocytes had already "out of whack" for quite a while (but, note that they are "out of whack" again, now by being abnormally low).

I do want to take a look at the neutrophils also, since they had been negatively impacted by the lymphocytes running amok. In the following graph of the absolute number of neutrophils (with added normal limit lines for 2.0 and 6.4 thousands of cells per microliter) during my clinical trial,...

...it can be seen that the neutrophils have gradually increased during the trial (and may even be slightly higher than normal right now), but it is also worth taking a look at the neutrophil count since I was diagnosed...

...because it illustrates one of the reasons that treatment was started (i.e., one of the reasons why my original W&W period had to end) - my neutrophils had become so crowded out of the bone marrow by rampaging lymphocyte production that they had starting dropping too much to ignore any longer. Both absolute neutrophil graphs do show the effectiveness of my treatment, however -- once the lymphocytes were brought under control in my marrow, neutrophil production did improve significantly.

OK, just one final graph for today's entry. This is one that's a bit more complicated in that it's a double graph, but it's one that I've used several times before, so, if you're a regular reader of this blog, you're already familiar with it. However, I did complicate it a bit with additional normal range limit lines, so it'll take a bit more concentration on your part to see what I am trying to show today. Ready? Well, OK, here goes...

Unlike all the previous graphs for today's post, which showed actual numbers of cells (in thousands per microliter), this one is showing proportionate percentages of two types of cells, lymphocytes (in red) and neutrophils (in blue). However, I have added limit lines for the normal percentages of these two types of cells (using the same color scheme), and that does make it a bit cluttered looking. However, besides showing the fact that my lymphocytes and neutrophils have reversed places as my #1 and #2 most common white cell types, as a result of treatment, it also shows that, while my white cells were unbalanced at the start of treatment, they did actually fall within the normal ranges for each towards the end of Part A, but then, immediately at the start of Part B, they became totally unbalanced in the opposite direction.

So, I am in much better shape than I was in at the time treatment began. There is a certain amount of "normalcy" in some of the graphs now, and in some of the numbers behind them. But, there are some serious abnormalities, too, the most obvious one being that my lymphocytes (both good and leukemic) have been kept artificially very low in number (and, as a result, I still take daily antibacterial, antiviral, and antifungal medications to help my suppressed immune system keep me as infection-free as possible).

Well, tomorrow will bring a new set of numbers, and I'll be watching, and waiting, to see just what might be going on... W&W...

 

Categories: Leukemia