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You are Here

Posted by Frederick Wasti
Apr 02 2013

I saw the above cartoon recently, and I did have a chuckle (or maybe two) over it, and I then thought that it might end up being an illustration in this blog. However, the more I thought about it, the more I realized that the cartoon was actually partially incorrect. While the past is indeed "the way things were", "Here" is ~not~ "the way they may be" - that is what the future represents. "Here" is what is fleetingly suspended ~between~ "the way things were" and "the way they may be". Part of the perplexed look on the face of the man in the cartoon may be due to the fact that he does not ~yet~ know "the way [things] may be". So, I decided to edit the cartoon a bit:

First, I had to "re-aim" the arrow so that it points ~between~ "the way things were" and "the way they may [yet] be". Then, I had to edit the "maybe", since "maybe" is not grammatically the same thing as "may be" (which is surely what the cartoonist must have actually intended). Finally, I added a dot to the ellipsis, since an ellipsis usually is shown as ~three~ (or more) dots in a row. (What can I say? "Once a teacher, always a teacher", I guess, which is ~not~ to suggest that I myself don't also make mistakes eminently worthy of correction - <grin>.) Anyhow, here's ~my~ version of "You are Here":

Anyway, getting to a more serious consideration of the past, of "Here", and of the future: As I've pointed out before, I do participate in a couple of CLL mail lists. (Well, the term "participate" is perhaps a bit overstated, since, while I do read what seem to be the relevant posts by others on the lists, I post to the lists myself only occasionally - I'd say that I'm not a big fan for "social media".) Recently on one of the lists there was a discussion of strategies for "where we go from here", prompted by a post by a "Susan" regarding her decision in 2003 to have a stem cell transplant. Since the discussion was indeed relevant for me, and since I did actually participate in it somewhat, I thought I'd share my part in the discussion here on the blog. [Please note that the excerpts below have been edited a bit for (I hope) clarity, and that the names of the other participants quoted have been changed.]

[Quote from "Robert":]

"I was diagnosed with CLL in March of 2012, with 17p deletion. Began FCR chemo in January, and am completing my third session, with as few as one to as many as three more to go. I’m otherwise in good health, 58 years old, and am now facing the decision to either go straight to an allogeneic stem cell transplant once in remission, or to wait for relapse before a transplant. I’m fortunate to have a large number of preliminary matches in the National Marrow Donor Program database. I’ve been advised by two CLL specialists to go straight to a transplant, given my age, health, and diagnosis. My own hematologist and transplant team are more wary of advocating one choice or the other, given the benefits and risks of both. I realize I’ll probably have to face the risks at some point, but my wife and I are weighing if I should wait and possibly have as much as a year or two of remission first? This is the dilemma. Right now I’m leaning towards going straight to transplant. I thought I'd post here before I decide, and possibly learn how others might have approached this."

[My response:]

Hello, Robert (and hello to the others reading this thread).

I am also 17p del (and also IGVH UNmutated, which is also not a good sign), so I was reluctant to try the FCR so-called "Gold Standard" because I was afraid that my results would be similar to what Susan had previously described for her situation. Of course, in 2003, there were not as many options available as there are now.

[Note: "Susan", also 17p del, had previously described how she had relapsed in 2010 after a seemingly successful 2003 transplant, although she was (obviously) still alive and fighting.]

I was first diagnosed in 2010, at 63 years of age, and I told my local hematologist/oncologist that I was not the least bit "excited" about trying FCR for 17p del. Instead I opted to go to Boston to the Dana-Farber for a clinical trial specifically for 17p del, and started that (after about 1 1/2 years of W&W) almost exactly a year ago.

Part A used Ofatumumab and HDMP (high dose Methylprednisolone), Part B used Ofa and Campath, as does Part C ("maintenance"), although ~much~ less intensively/frequently than in Part B. I did reach a so-called "Complete Remission" (CR) (undetectable disease [ < 0.01% CLL / WBC ] in my marrow) back in November, and I am still doing very well on Part C "maintenance", which I may remain on for up to two years in the trial, or I could elect to have a transplant at any time.

I did meet with D-F stem cell transplant team members way back in Part A, and I told them at that time that I was not yet convinced that an SCT was the best direction for me to proceed towards. I stated that I hoped that some of the new meds "coming down the pike" (Ibrutinib, etc.) looked very promising, and, IF so (and that's a big "IF"), they seemed preferable to an SCT.

The D-F SCT doc told me that such meds were as of yet unproven in the long term (and he was correct, especially since he stated this last spring). He also claimed that a SCT was my best chance for survival - he stated (rather bluntly), "With 17p del, and without an SCT, you'll be dead in two years." Sobering, yes, but I was still not convinced that an SCT was the best choice for me.

Despite my expressions of doubt about an SCT, the SCT team did complete a donor search on my behalf more recently, and informed me that there is a 10/10 match available for me at the moment. However, I still want to avoid an SCT, if at all possible (although, with my current CR status, I could still give the "go-ahead" at any time if I so desired).

If this were just a few years ago, an SCT would probably have been my reluctant choice. On the other hand, if this were a few years from now into the future, AND IF some of the various new experimental weapons against CLL do eventually pan out, I would dismiss an SCT in favor of using one of them without much questioning. However, right now, as I "watch and wait" (so to speak), and as long as I can remain in (or at least close to) CR status, I am putting my faith in the new drugs now in clinical trials.

Well, that's my point of view (subject to change, of course), and I am hopeful for the future...

I wish you well, and I wish you wisdom in making your own decision.

Carry on then...


[Quote from "Joan":]

"Dear Fred was wondering what percentage of 17p you have. My boyfriend is also unmutated, was 13q14.3. about 85% but now 17p13.1 4.5% showed up and also 6q21. Currently he is having FR but was wondering if he should be having F at all? He got these results from fluorescence in situ hybridization (FISH) testing back after we started the FR. Is the 17 more serious at a higher percentage how long does it take to increase? thanks Joan"

[My response:]

Hello, Joan.

My numbers show a bit of a "roller coaster ride", in that some of the tests are of peripheral blood while others are of bone marrow aspirates and/or cores, and some tests were FISH tests, while some of the others were from karyotyping, and some were from MRD (minimal residual disease) testing. Then, more than one lab was involved in all of these tests. Furthermore, there's a lot of granularity in the karyotyping results due to the small number of cells actually examined. So, there's a bit of "apples versus oranges" involved in comparing the following numbers:

7/22/2010 (time of diagnosis) - FISH testing of peripheral blood showed 68.5% of my cells with 17p del, while karyotyping showed "only" 25% (5 out of 20 metaphase cells examined) had 17p del.

9/8/2010 - FISH testing of peripheral blood showed 48% 17p del.

3/14/2012 - Karyotyping of bone marrow tissue showed 82.5% (10 out of 12 metaphase cells examined) with 17p del.

The results above are all pre-treatment - the clinical trial that I briefly described in my last post began on 3/21/2012 (and the above 3/14/2012 test was performed just one week before treatment began).

7/6/2012 - Karyotyping of bone marrow tissue showed 25% (5 out of 20 metaphase cells examined) with 17p del, while MRD testing showed 6% CLL cells (which, in my case, are likely all 17p del monoclonal cells).

8/13/2012 - MRD testing of peripheral blood showed < 0.1% CLL cells (below the sensitivity level of the probe, at 0.1%), so that would mean < 0.1% 17p del cells, too.

9/28/2012 - Karyotyping of bone marrow tissue showed 10% (1 out of 10 metaphase cells examined) having 17p del, while FISH testing showed "2.5%" 17p del (which is "into the noise" of the FISH probe's sensitivity of 5%, and may not be significant), and MRD testing showed 0.02 % CLL cells (therefore no more than 0.02% 17p del cells).

11/9/2012 - FISH testing of bone marrow tissue showed "less than 3%" with 17p del, but karyotyping was not performed, because "no metaphases could be analyzed from this specimen" (which I assume was indirectly a good sign, showing less active cell division in my bone marrow), and MRD testing showed < 0.01% CLL cells (the probe's sensitivity level is 0.01%) (so that < 0.01% of cells would be 17p del).

Well, the above are what you asked for, but, as I said, it's a bit of a "roller coaster ride". The good points to note are that, while the general trend was upward before starting treatment, the general trend has instead been downhill during the trial, and the last part of the "ride" did end up way down ("close to the ground", so to speak).

I will say that part of my aversion to FCR has been that the F and C (neither usually being very effective on 17p del cells) might not do very much good for me, and they, instead, could do more harm than good by bringing about an increase in 17p del cells through clonal evolution (as has apparently did happen in the case of Joan's boyfriend). Instead, I chose to be treated with Ofatumumab (not unlike the R of FCR) along with high steroid doses, followed by more Ofa and some Campath, all to chase the 17p del CLL cells out of my lymph nodes (HDMP) to make them easier to kill in the bloodstream (Ofa), and then to also attack them in the marrow (Campath), without using any intentionally mutation-causing agents (such as F or C) to do so. Anyhow, that's my (perhaps oversimplified) strategy statement.

As for your specific questions, "Is the 17 more serious at a higher percentage[?] how long does it take to increase?", I can't say for certain, but I would say that the first answer has to be "yes", while the second answer is likely (with 17p del) to be "all too soon", and so I do think that avoiding treatments that make it easy for 17p del cells to actually increase makes for a good overall strategy.

Carry on then...


[End of quotes]

Yesterday happened to be a "Dana-Farber Day" for us, involving the "usual" blood tests, pre-meds, and Campath injection. The only part of yesterday's "festivities" that was not "usual" was a meeting with Dr. Fisher before we left D-F. "Things" (blood test results and my overall physical condition) seem to be going along quite well, so the meeting was mostly pretty routine. (Routine is good.)

As for the blood counts specifically, well, there ~still~ are no significant changes to be seen - my counts are all still just about where they were when I was "graduated" from Part B to Part C back in November, even though I am now being treated on a "leisurely" once-every-other-week basis. So, I do have to say that the stability of my blood counts continue to amaze me - there is no evidence that anything is changing in a negative direction. (I know, of course, that I still have zillions of nasty CLL cells inside me, but the evidence does not even suggest that they are yet making any sort of a comeback yet.) Remarkable. :-)

OK, I did spare you blog readers from having to look at any graphs in my last post, but I won't do so this time. The graphs below do not show any significant recent changes, but I did take the time to put some vertical lines on each of them, to show the beginning and end of each clinical trial part, A, B, and C (although, of course, I maybe should have left out the right-hand line for Part C, since it could still go on for another year-and-a-half).

The total white cell count...

...continues to stay within the normal range. It can be seen from the above graph that Part A reduced the white cell count so much that I already had a normal total number of leukocytes by the time Part B started, and I have stayed basically in the normal range throughout Parts B and C (even though changes in the relative proportion of the individual leukocyte types were indeed still taking place, as the following graphs will illustrate).

The most significant difference in blood counts that has occurred during the trial is in the relative proportion of lymphocytes (red curve) and neutrophils (blue curve), ...

...where it can be seen that the percentages of each have significantly changed during Parts A and B (most dramatically at the start of Part B), and that they continue to be (intentionally) quite abnormally skewed throughout Part C.

The main reason for the changes in the above two graphs is due to very large changes in the absolute number of lymphocytes, ...

...which have been the intended targets of the drugs I've been given throughout the trial. In the above graph it may appear as if the lymphocytes have been reduced to zero. However, a graph with an expanded scale for the vertical axis, ...

...shows that they are not really quite zero after all, but that they are still relatively quite close to zero nonetheless.

There has been a small but important overall increase in the absolute number of neutrophils as well, ...

... and so, while the biggest change in individual white cell numbers has involved the lymphocytes, the neutrophils have also contributed a little toward the rather dramatic proportional difference.

Interestingly, the monocytes...

...have seemed to be "innocent bystanders" in the battle going on in my body between the anti-leukemia drugs I've been taking and the now decimated population of lymphocytes. It is still a bit surprising to me that the number of monocytes did drop somewhat in Part A, since, to my knowledge, I didn't think that either Ofatumumab or Methylprednisolone would interfere with monocytes. On the other hand, it is not surprising to see that Part B reduced my monocytes to very low numbers, since Campath/Alemtuzumab does kill cells with CD44 proteins on their surface, and, among the white cells, it is the monocytes and lymphocytes that exhibit such CD44 surface molecules. So, it is gratifying to see that, in Part C, with its greatly reduced frequency of Campath injections, the monocytes have been able to bounce back a bit.

So, everything appears to be doing what the clinical trial was designed for. Everything is certainly not normal, and I am certainly not "cured", and I've had to trade my immune system away to get to this point, but I am still alive in the "Here and Now", after the huge physiological changes that have occurred over the past year or so, and I am optimistic for the future, even as uncertain as it may be.

I am Here.

Categories: Leukemia