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Side Effects (#2)

Posted by Frederick Wasti
Apr 28 2012

In my previous post on side effects (#1) I stated, "when all is said and done, I am convinced that it is the Methylprednisone that gives me the strongest little medley of side effects of any of the weapons in my anti-CLL arsenal, and I'll cover the 'joys' of high dose Methylprednisone in my next entry". Well, here is that next entry - <g>.

In Part A of the clinical trial, I am given Methylprednisone every day I am at Dana-Farber. I receive high doses (2,350 mg) of it ("high dose Methylprednisone" = "HDMP") on the three days of the first week of each 28-day cycle, but I am also given relatively small doses (50 mg) of it on each of the other Wednesdays, as one of the pre-medications to prepare me for the Ofatumumab. I don't really think I am bothered much by the 50 mg doses - it's the large 2,350 mg doses, given each Wednesday, Thursday, and Friday of the first week of each cycle, that seem to cause the most profound side effects of any of my medications.

I have to admit that I am willing to blame HDMP for all of the effects listed below. However, while some of these must clearly be due to HDMP, it is possible that some of them might be unrelated. Logically, I think (<g>), I tend to assume that any side effects I experience during the week or so that begins with being given three large doses of Methylprednisone, but which I do not also experience during other weeks, can be blamed on HDMP. However, it is also possible that there is more going on inside me than can be so easily explained.

In comparison to the effects listed in my last blog entry, there is one aspect about the effects the large doses of Methylprednisone that is quite different. Unlike the other meds, whose effects generally start fading away once the medication has been administered (or shortly thereafter), the multiple effects from HDMP seem to come and go in a sequence over a time period that starts with the three days of infusion and then continues, with some of the effects not appearing until several days later. (And, this is especially true regarding the most recent "Methylprednisone week", where some of the effects seemed more pronounced than the first time around.)

The first side effect that I notice each time I am given HDMP is a metallic taste in my mouth (much like that of copper), which persists while the infusion is going on and then for a short while afterwards. This, of course, is a minor effect, just a mere nuisance.

However, as the infusion progresses, I start to notice what I call "foggy vision" developing, which persists all that day into the evening, and may even be slightly evident the next morning. This "foggy vision" is not caused by objects around me appearing out of focus - the effect seems mostly due to a lack of overall contrast, with all colors appearing very unsaturated. The "foggy vision" is sometimes almost comical to experience, because of the conflict between my eyes (which "show" there is fog all around me) and my conscious mind (which knows this to actually be an illusion). (Of course, it probably is part of the brain - and not actually my eyes - that is being fooled by the HDMP.)

Another visual effect that occurs with the HDMP is what I call "busy vision". This is not obvious if my eyes are open and receiving "normal" visual stimuli, but becomes more evident if I close my eyes. This "busy vision" sometimes displays apparent star fields of random blinking points of light, where each "star" lights up for a couple of seconds or so and then disappears. It's an interesting effect, I suppose, but any interest in it is short-lived - <g>. Sometimes this "blinking stars" effect is replaced with a matrix of shifting colored lines, but this seems to be less frequently "enjoyed". In any event, with my eyes open in daylight or in normal room light, external visual stimuli seem to swamp the "busy vision" effects.

But, at night, when I'm hoping to go to sleep, the "busy vision" can be all too obvious to be easily able to do so. With the lights off, it doesn't really matter if my eyes are open or closed - without any external visual stimuli to overwhelm the "busy vision", it is a constant distraction that can make getting to sleep a bit of a challenge (aided, no doubt, by the fact that the HDMP has also by this time made me a bit more "wired" than usual, as well).

Although it probably starts on the first infusion day of "HDMP week", something that becomes more obvious on the following several days is what more than one nurse at D-F has called "steroid glow". That is to say that my skin becomes flushed in appearance, almost as if I had a mild sunburn - a nice ruddy glow. Cute - <g>.

Generally, by the weekend, I seem to become fairly "jittery" (that's about the best word I have for it). On the three infusion days this effect starts to appear, but it seems to peak on the days right after the infusion days. I suspect that this may be more of a nuisance to Diane than it is to me, but it did seem to be more intense on this past weekend (as compared to the beginning of the clinical trial), where the "jitteriness" at times caused me to feel more frantic (almost panicky) than I really cared for.

One of the D-F nurses, back in my first "HDMP week", while describing some of the HDMP side effects, predicted that "You'll crash on Tuesday". Well, Monday and Tuesday do seem to end up being "down days", as I assume the HDMP is "working its way out of my system". Any "jitteriness" from the weekend is replaced with a dose of sadness, lethargy, and depression. Not nice. 'Nuf said.

Also starting on Monday or Tuesday, and continuing for another couple of days or so, are "hot flashes". With these, without warning, all of a sudden I find myself feeling overly hot and sweating a bit. This is almost overwhelmingly uncomfortable, but - fortunately - each "hot spell" does not seem to last very long.

More troubling is the weakness that I seem to develop at about the same time as I'm getting the "hot flashes". I am already frustrated with how fatigued I had become due to leukemia, and, for most of the time after the trial was underway, I have felt a bit less fatigued (and therefore more encouraged) than before the trial started. So, to have to go through a couple of days of feeling pretty feeble is discouraging (especially when I don't know for sure, as I am going through it, that it will indeed be only temporary).

As can be seen from the above, high dose Methylprednisone is "not for the faint of heart" - <g>. However, all of the above is tolerable or at least bearable, at least so far for this "lab rat" (<g>) - just as long as I believe (and I do) that the HDMP (and Ofatumumab, etc.) will do more damage to my CLL lymphocytes than to the rest of me - in other words, the ~main~ effects are far more important than are these mere side effects. :-)


Categories: Leukemia

Side Effects (#1)

Posted by Frederick Wasti
Apr 26 2012

During Part A of my clinical trial at Dana-Farber I guess I take some rather potent medications (and I will take another, potentially more potent one - Alemtuzumab - in Part B, too).

The good news is that, technically, none of these meds fully qualify as a "chemotherapy" drug. (I'll talk about the differences between what is and what is not a chemotherapy drug in another post sometime soon.) Because of the fact that none of these is actually a "chemo" drug, the long term side effects are (on paper, at least) kept to a minimum.

However, there certainly are a number of side effects that I am experiencing as the trial proceeds, and I would like to mention some of them here.

I first want to make clear, though, that none of the side effects are debilitating or intolerable. (And I'm not a "no pain, no gain" kind of guy anyway.) Therapy for leukemia is not expected to be the proverbial "walk in the park", and my opinion so far is that it isn't. However, so far, I have to believe that the medications that I am absorbing are doing a lot more harm to my aberrant lymphocytes than they are doing to the rest of me.

One reason for bringing up this little catalog of side effects now is that I have found some of the "annoyances" becoming more pronounced lately. Specifically, having just gone through three days of high-dose Methylprednisone last week (as I also did during the first week of the trial back in March), I have found that the side effects seemed more significant than that first time around.

Going back to the early days of the trial, the most pronounced side effect I encountered was the intense groggy stupor that an intravenous 50 mg dose of Benadryl can bring about. I am administered Benadryl each Wednesday, as a "pre-medication" before I am given my dose of Ofatumumab. The good news now is that I no longer am given 50 mg of the Benadryl - after the first couple of times, where I seemed to tolerate the Ofatumumab pretty well, the dose of Benadryl has been mercifully cut back to 25 mg, and I am no longer left feeling like a 400 pound walking-dead zombie after the Benadryl infusion progresses, but something more like a 300 pound Rip van Winkle. I guess that's progress (?). However, I do have to say that the Benadryl grogginess this past Wednesday did seem more pronounced than usual.

As for the Ofatumumab, I do have to say that its side effects are possibly the least of any of the medications I have been receiving (except possibly for the innocuous two Tylenol pills I am given as another Wednesday pre-medication). It does take a few hours to infuse the Ofatumumab into my bloodstream, and I gradually start to get a stronger and stronger "heavy head" as the infusion progresses, but it never even morphs into an headache. Nonetheless, by the time the Ofatumumab infusion has finished, I am left with a pronounced "washed out" feeling, but it's not overwhelming by any means, and it's generally gone by the next morning anyway. So, I am left hoping that Ofatumumab is treating my leukemia cells more rudely than it is treating the rest of me.

But, when all is said and done, I am convinced that it is the Methylprednisone that gives me the strongest little medley of side effects of any of the weapons in my anti-CLL arsenal, and I'll cover the "joys" of high dose Methylprednisone in my next entry.

Categories: Leukemia

Uh-Oh - Plateau

Posted by Frederick Wasti
Apr 25 2012

A week ago I said, "For the blood test results after the fourth week of testing, there was a bit of a disappointment, in that the white cell counts (including the differential lymphocyte count) did indeed go down once again, but not by all that very much this time, making for a shallower slope for the curves on the total white cell graph and the lymphocyte graph - still in the right direction, but not so determinedly so. (Maybe I'd been "spoiled" so far.) Bummer..."

Unfortunately, the optimism that we had felt then - that three more rounds of Methylprednisone last week might have "jump started" a renewed decline in white cells - has not been realized.

First, let's take a look at the total leukocyte count since the clinical trial started:

As can be seen, the last three Wednesday blood tests do not show a continuing downward progression.

If we look at the last three Wednesday results in a different context, in a graph of the total leukocytes from the time of diagnosis, it looks like this:

If you look quickly, it maybe all looks like good news. However, if you zero in on the most recent three results (in the circle), what is going on in my blood is that my total white cells are simply no longer continuing to go down.

Let's look at the lymphocytes specifically this time - here is what has been happening to the lymphocytes from the time of diagnosis:

Not surprisingly, since the lymphocytes had become my most abundant type of leukocyte, and since it is the lymphocytes that the treatment is supposed to be bringing down, this graph looks a lot like the second graph, that of the total leukocytes since diagnosis.

We did speak separately today with nurse Kathleen McDermott and nurse practitioner Michele Walsh about this seeming lack of continued progress. Both expressed the same disappointment, but we all realize that this is "a work in progress". The counts ~may~ start to come down again as we continue the clinical trial Part A protocol (or they may not). It is possible that dramatic changes will start taking place again during Part B (which involves Ofatumumab once again, but without high doses of Methylprednisone alongside it, and with the addition of Alemtuzumab to the arsenal).

It is also quite possible that substantive events are going on right now, even if they do not seem to be showing up in blood test results. Lymphocytes are found in three main areas of the body - the bone marrow, the blood stream, and the lymphatic system (i.e., the lymph nodes and spleen). Blood counts can only show what is going on in the blood, and are quite oblivious to possible changes in the lymph nodes and marrow.

I am scheduled to have a CT scan on May 4th, so we may be able to learn of some positive changes to my lymph nodes and spleen at that time. (There were only two lymph nodes that I could personally detect previously, both below my right ear, just behind the angle of my jaw, and those "shrank to nothing" on the first day of treatment, but I/we have no idea as to what has happened since then to the rest of my internal lymph nodes and my spleen, which were previously known to be enlarged) - that's why, of course, this CT scan is to be made.

There is also some evidence of positive changes in my bone marrow, both from my improving platelet counts and from the bone marrow biopsy ("BMB") I had back on March 14th, and I will likely have another BMB in a few weeks, at the end of Part A. So, we may have further good news regarding the bone marrow still forthcoming.

I guess all of this is to say that, while it is disappointing that the blood tests have stopped showing dramatic improvements, it still is possible that good things are continuing to take place. The fact that all is not as predicted is at least partially because all of it cannot be predicted - a clinical trial is, after all, an experiment, right?

Categories: Leukemia

17p, TP53, and Me (#3)

Posted by Frederick Wasti
Apr 23 2012

[Please note that, if you haven't already made your way through my previous two posts on "17p, TP53, and Me", below, I would ask you to try doing so before proceeding with this continuation - Thanks a lot.]

Well, whether or not you were able to follow along with my attempts to connect p53 deletion to TP53 malfunctioning, to uncontrolled growth, and to difficulty with therapy, you may be able to appreciate this third "17p, TP53, and Me" installment.

During the latter half of the Twentieth Century, medical methods of treating CLL often met with some success. Many CLL patients seemed to show a naturally slow leukemic growth rate anyway (in other words, their leukemia was indeed more chronic than acute). Many other patients did receive benefit from some of the earlier forms of chemotherapy that were used with them. However, there were always a few CLL patients who displayed rapid progression and who also failed to show much response to the standard treatments that were often successful for many other patients. We now know that these differences in outcomes are due primarily to the molecular basis of individual differences between CLL patients. (Please note that 17p deletion is not the only genetic defect that impacts CLL, but, as will be pointed out below, it is the most damaging genetic effect to own.)

As was stated just this year, "Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, with some patients displaying an indolent clinical course with a similar survival to that of normal individuals, whereas others display a poor outcome with a median survival between 1 and 5 years". So, I would like to devote this blog entry to a smattering of quotations from recent scientific literature relating the effect of genetics on disease progression and treatment success. (Yes, there are a few new technical words included here and there, but I don't think it's worth trying to explain each and every one of them - the overall gestalt of the quotes below will convey the general situation adequately, I do believe.)

[2007] "Independent prognostic factors associated with rapid disease progression and short survival times include 17p- (approximately 67% to 75% 2-year survival). [...] 17p- predicts for treatment failure with alkylating agents, as well as fludarabine, and short survival times. [...] Genes potentially involved in the pathogenesis of CLL have been identified in a subset of cases with 17p13- (p53). For example, p53-pathway based therapies, such as fludarabine, appear ineffective in patients with p53 genetic abnormalities associated with resistance to treatment. In addition, 17p- correlates with mutated p53 along with poor response rates and short duration of response to the standard therapeutic options, including alkylating agents, rituximab, and fludarabine, and with short survival duration in patients with CLL."

[2008] "Patients with advanced CLL and 17p deletion have a very poor prognosis even after intensive chemotherapy."

[2008] "The 17p13.1 deletion that causes loss of the p53-encoding TP53 gene is the most powerful predictor of a poor response to conventional therapy and shortened survival in patients with chronic lymphocytic leukemia (CLL)."

[2009] "About 10 percent of people with CLL have deletions in the short arm of chromosome 17 (del 17p). The critical gene in this region that is typically deleted is TP53. People who have CLL with del 17p tend to have higher-risk disease and usually do not respond as well to standard initial therapy."

[2009] "Deletion of 17p in chronic lymphocytic leukemia (CLL) is associated with resistance to conventional therapy and a poor clinical outcome."

[2010] "Although the deletion of 17p is associated with poor outcome in different malignancies (e.g., acute myeloid leukemia, myeloma, and CLL), its impact on outcome is particularly striking in CLL."

[2011] "Deletion 17p is found in ~7% of CLL patients [...] and confers the highest risk. While the deletion frequently encompasses most of short arm of chromosome 17, the minimally deleted region always involves 17p13, the locus of the TP53 gene encoding the tumor suppressor p53. In addition, the majority of CLL patients with monoallelic deletions of 17p have point mutations in the remaining TP53 allele, thus completely inactivating a critical component of the DNA damage response pathway. It is well-established that CLL patients with p53 inactivation respond poorly to conventional fludarabine or alkylating agent-based regimens, possibly because both agents require p53-dependent pathways to induce cell death. Patients who do not respond to fludarabine have a median overall survival of ~10 months."

[2011] "Mutations of TP53 were found in 7.6% of patients. There was no significant correlation between TP53 mutations and age, stage, IGHV gene mutations, CD38 and ZAP-70 expression, or any other chromosomal abnormality other than 17p deletion, in which concordance was high (96%). TP53 mutations were significantly associated with poorer overall response rates (27% v 83%) and shorter progression-free survival (PFS) and overall survival (OS); 5-year PFS: 5% v 17%; 5-year OS: 20% v 59%)."

[2012] And my favorite description of all: "The 17p deletion is the mother of all poor prognostic factors for CLL."

Well, all of the above does indeed sound a bit bleak, but there is hope, too. Now that CLL scientists are aware of the significance of a number of distinctive molecular genetic situations affecting CLL, efforts have been made to work on different modes of therapy to work around them, and that brings me to my current situation: Instead of undergoing the so-called "gold standard" treatment known as "FCR" (named for a cocktail of Fludarabine, Cyclophosphamide, and Rituximab, which does work quite well for some non-17p patients), I am participating in a clinical trail at the Dana-Farber Cancer Institute in Boston that is specifically aimed at trying to aid 17p-deleted patients such as myself, using therapies that do not depend on affecting the TP53 gene in order to slow down the growth of leukemic cells.

And this is all very exciting stuff !!! (<g>)

Categories: Leukemia

17p, TP53, and Me (#2)

Posted by Frederick Wasti
Apr 22 2012

[Please note that, if you haven't slogged your way through my earlier post entitled "17p, TP53, and Me (#1)", below, you really should tackle that before starting with this continuation - Thanks.]

In my last post, "17p, TP53, and Me (#1)", I tried to introduce the concept that chromosome 17 can suffer from a deletion. I pointed out that such a deletion is deleterious for any CLL patient, as it tends to cause a more rapid disease progression as well as tending to increase the difficulty of therapy using standard treatments. What I would like to try to do in this entry is to explain a bit about why this is so.

As I have mentioned previously, most body cells are supposed to have a finite life span, and they ordinarily are supposed to die (or be killed) when their normal life span is up. This natural programmed process of cell death is known by the term "apoptosis" ("ay-pop-TOE-sis"). Apoptosis is generally caused by either some sort of a cellular stimulus or by the lack of some sort of a cellular suppressor.

(Yes, I know this is starting to sound a bit technical, but please hang in there just a bit more - please remember that you do ~not~ need to understand every detail to "get the big picture".)

Now let me try to get to the significance of the "TP53" (sometimes just called "p53") in the subject line. In this case the "P" or "p" is not being used to refer to the short "p" end of a chromosome (as it was in "17p"), but is instead standing for the word "protein". Remember that genes control the production of proteins, and so genes are sometimes named for the proteins they control. In this particular case, "TP" stands for "tumor protein", and TP53 has been found to be a very important protein that regulates apoptosis - to encourage cells to reproduce when cell growth is desirable, but to also act as a "brake" on cell growth when excess growth would only lead to cancer. In other words, the TP53 gene is a special tumor-regulating or cancer-regulating gene, ordinarily capable of bringing on apoptosis in a cell whose time is right to die.

As it turns out, improper functioning of the TP53 gene is a significant factor in approximately one-half of human cancers. When the TP53 gene fails to apply the brakes in a cell with defective DNA (i.e., a cell with a mutation that cannot be corrected), the mutated cell can start growing in number uncontrollably, and that is, of course, what cancer ultimately represents - uncontrollable reproduction of defective cells that have lost the ability to die naturally.

Now, to connect the TP53 gene back to my earlier description of chromosome 17p deletion, the fact is that, when a 17p deletion occurs, the TP53 gene is lost, since it is located near the end of the 17p chromosome. (It is also possible for the TP53 gene to be mutated without a 17p deletion, but the effect is still the same.) In CLL, the absence of functioning TP53 genes in lymphocytes (generally due to 17p deletions) leaves the lymphocytes with no way to die - they have no mechanism to undergo apoptosis.

Now the good news for over 90% of CLL patients is that, since their lymphocytes do have functioning TP53 genes, their cells do have, at least to some extent, the ability to undergo programmed death. Furthermore, standard drugs that can encourage the TP53 gene to suppress cell division can be effective in slowing cancer growth down.

But, the bad news for those of us CLL patients who have 17p chromosome deletions is that cancerous cell growth is naturally much more rapid (because there is no TP53 suppressor "brake" to counteract excessive growth), and standard therapies that work to trigger the TP53 gene into bringing about apoptosis (which do help in most CLL patients) become rather ineffective when used in those of us who lack functional TP53 genes.

Categories: Leukemia

17p, TP53, and Me (#1)

Posted by Frederick Wasti
Apr 21 2012

Well, so far in this blog I have been mostly able to avoid getting bogged down in such things as DNA, chromosomes, and genes, etc. However, it is now time to try to cover the relevance of some of these issues, and not just for any old abstract reason, but for the very concrete reason that genetics will have a great impact on my life with CLL - how I should most successfully be treated, how long may I survive, etc. - and these are indeed practical matters much closer to me than the realm of the abstract to be sure.

I do apologize for using a lot of terminology in these discussions (which will take more than one blog entry to complete). However, I do feel that it is possible to come to grips with enough of the following descriptions and explanations ~without~ having to understand it all fully. (Heck, I don't understand it fully myself - <g>.) So, I am asking you to please try to follow along with at least some of the main points in my explanations, ~without~ feeling any need to understand every last bit of minutiae. OK? (Thanks.)

First, let's take a quick look at a typical human "karyotype" - the pattern of chromosomes that is found (usually all tangled up, however) in nearly all of our body cells. (In a karyotype diagram, the chromosomes have been artificially manipulated to be neatly spread apart and organized into their homologous pairs, as shown below.)

As everyone is aware, nearly all of our cells contain chromosomes (23 pairs of them), and on these chromosomes are all the genes that control all of our heredity. The actual control of everything is handled through the genes determining how every protein (every enzyme and every structural protein in our bodies) is produced. Ordinarily this control is invisible to us as we live, but mistakes - "mutations" - do occur occasionally. Most mutations can be corrected and/or removed by remarkable cell machinery, especially early in life. However, the rate of mutations does tend to increase with age, and our abilities to neutralize their effects does simultaneously tend to decrease with age. Such is aging...

Most cells in our bodies are supposed to have finite life spans - that is to say that most cells are supposed to be born, to live a functional life, and then to die, to make room for newer, more productive cells to take their place. But, as we know with forms of cancer this does not properly happen. Cancer cells lose the ability to easily die, and we all know how serious that problem can become.

Chromosomes, which exist in pairs, can be thought of as being strings of genes. The genes also exist in pairs, with each gene being located on each matching member of a pair of chromosomes. Our 23 pairs of chromosomes are numbered by size, and the pair in question here is the 17th pair. (If you're on the ball here, you have probably just figured out where the "17" in this entry's subject line comes from - <g>.)

Under the right conditions, each chromosome has approximately the shape of an "X", with the connecting point of the "X" sometimes close to the middle for some of the chromosomes and sometimes close to the end in some of the other chromosomes (making a few of them almost seeming to be "Y" in shape). In the terminology of genetics, the short ends of the X shape are referred to as the "p" ends and the longer ends are the "q" ends. (And now you may be recognizing why the first three characters in the subject line are "17p" - <g>. As it turns out, a high percentage of my leukemic lymphocytes have a deletion on one or both of the short ends of my 17th chromosomes.) (This deletion is not found in 99.999% of the cells in my body, but is found only in my mutated leukemia cells.)

If we take a closer look (just for simplicity) at just one half of a 17th chromosome (the "p" short end to the left and the longer "q" end to the right, it would look like the following - the codes along the side are how scientists map locations on each chromosome). I have added a red arrow where the unfortunate 17p deletion occurs in a few of us CLL patients (the exact location is known as 17p13.1):

It turns out that having a 17p deletion (sometimes referred to as "17p-", where the minus indicates the missing deletion) is significant in some types of cancers, some more so than in others. In the case of my particular leukemia, chronic lymphocytic leukemia (CLL), it does make a large difference. A CLL patient who does not have this deletion has a much higher probability of the disease progressing quite slowly, as the name "chronic" would suggest. However, in contrast, those 5% or 10% or so of us that have CLL and also have a deleted 17p chromosome turn out to have a form of CLL that progresses much more rapidly (almost as if it were an acute form of leukemia) and also does not respond well to conventional chemotherapies used for most CLL patients.

I will try to get a little closer to the bad news about having the 17p deletion in my next entry. (In the meantime, please do try to bear with me here - it is ~not~ necessary to understand all of this to succeed at following my story, so please just try to be patient and you ~will~ absorb enough for this to be useful - trust me, please.)

Categories: Leukemia

Cycle 2 Day 3

Posted by Frederick Wasti
Apr 20 2012

Well, the "busy first week" of Cycle 2 (the first week of every cycle in Part A of the clinical trial is a "busy week", involving three days of infusions) is over. The noticeable after effects on Day 1, which involved several infusions, including full dose Ofatumumab, were a little stronger than expected (although still quite tolerable), while the noticeable effects from Days 2 and 3, which involve only full dose Methylprednisone each day, were/are pretty tame. As I write this, on Friday (Day 3) afternoon, I am feeling pretty good - the only effect that is pronounced is the "foggy" vision I have as I type (things are not out of focus, but I just notice a subdued color sense and overall lack of contrast, and I know that this is likely to be gone by tomorrow morning anyway).

I did have a visit from Dr. David Fisher this morning, to go over some questions I had, and I'll come back to most of that later. But, first I would like to go back to my cursory description of Wednesdays good and not so good results, bringing in some graphs to illustrate this time:

I did mention in the 3/18 blog entry that, "For the blood test results after the fourth week of testing, there was a bit of a disappointment, in that the white cell counts (including the differential lymphocyte count) did indeed go down once again, but not by all that very much this time, making for a shallower slope for the curves on the total white cell graph and the lymphocyte graph - still in the right direction, but not so determinedly so. (Maybe I'd been "spoiled" so far.) Bummer..." Well, let's take a look at some graphs:

First, here is a graph of the total leukocyte count since starting the clinical trial (and a couple of pre-trial visits) at D-F:

It can be seen from the above graph that my total white cell count did go down again in Wednesday's blood tests, but the rate of decline was considerably smaller than the decline from previous treatment weeks.

To put these data into more of a historical context , let's take a look at how the total white cell count has varied since the time of diagnosis:

It can be seen (if you look closely - <g>) in the above graph that the results from Wednesday's tests just barely made a slightly lower dot at the end of the curve.

I did discuss with Michele Walsh (Dr. Fisher's nurse practitioner) on Wednesday, and with Dr. Fisher himself this morning, as to their thoughts about the slowing of the total leukocyte count decline. Both separately suspected that, not having had the full dose of Methylprednisone since Week 1 of Cycle 1, the Ofatumumab, perhaps acting more or less alone by the time Week 4 of Cycle 1 came along, was not able to be as effective by itself. (I had known from my own research that CLL rarely responds to "single-agent therapy", and that it usually requires two or more agents acting together and acting synergistically to make a dent in the disease.)

Both Ms. Walsh and Dr. Fisher expressed the hope that, since I did receive three rounds of full dose Methylprednisone (along with a round of full dose Ofatumumab) this week, that next week's blood test results may show a renewed rate of decline. (We all do have to remember that this is an ~experimental~ clinical trial, and not all is known to occur according to plan.) (Of course, all may not go according to plan for every patient undergoing even so-called "proven" therapies - <g>.) I am optimistic that both Michele Walsh and Dr. Fisher are correct - it all makes sense to me.

Now let's take a more specific look at how the lymphocytes themselves have changed (both as a percentage of the total white cell count and as an absolute number of cells per microliter):

As with the total leukocyte graphs, it can be seen that the lymphocytes have also declined once again during Week 4 of Cycle 1, but that the rate of decline had leveled off quite a bit. However, the shared optimistic expectation by all concerned is that, after receiving three rounds of full dose Methylprednisone along with a round of Ofatumumab this week, the lymphocyte count will lead a downhill charge, taking the total lymphocyte count along for the downslope ride. :-)

Remember, though, that there was also good news from Wednesday's blood tests: I also pointed out in the 3/18 post that, "On the other hand, my platelet count continues to rise, and this indicates that my bone marrow is definitely still improving - i.e., it is still being cleared of excessive lymphocyte stem cells, and of their excess new and immature offspring. :-)" So, let's take a look at how the platelet graphs appear:


Notice in the above two graphs that the platelet counts had been in decline until treatment started, but had started improving once treatment began. This is significant in at least two respects:

1. Since platelets are necessary for proper clotting of blood, it should be evident that a declining platelet count is not good news. In fact, with CLL, having a platelet count drop much below 100 is often an indication that treatment should be begun and that the time of "Watchful Waiting" is over. (The normal platelet count should be a lot closer to 300 or so - that's about 300,000 per microliter or per cubic millimeter.)

2. Since platelets are manufactured in the bone marrow, a declining platelet number is evidence that the marrow is filling up with too many aberrant lymphocyte stem cells and their immature offspring, crowding out other healthy marrow cell processes. But, conversely, a rising platelet count is evidence that the clutter of excessive lymphocyte production is starting to be cleared away, and that is ~very~ good news indeed.

So, while Wednesday's blood test results were not quite as gratifying as were those from other recent Wednesday, there was still some good news to report, and we all have some guarded optimism regarding next week's blood test results. :-)

Diane and I did have a good discussion with Dr. Fisher this morning about the possibility/probability of undergoing a stem cell transplant procedure sometime soon, but I will leave a discussion of this until my next blog entry. (So as to not keep you in too much suspense until then, I will let you know here that Dr. Fisher - as well as Michele Walsh on Wednesday - said that there is no reason to go rushing headlong into a stem cell transplant just yet, even though I may want to consider one in my not too distant future.)

Categories: Leukemia

Cycle 2 Day 1

Posted by Frederick Wasti
Apr 18 2012

Hi there. For anyone checking in to see how I am doing after today's trip to Dana-Farber, well, I am doing "OK". Today was the first day I was given the full dose of Methylprednisone and the full dose of Ofatumumab together, and it was maybe just a little more than I bargained for - <g>.

Back on Day 1 of Cycle 1, I did also have the full dose of Methylprednisone along with the Ofatumumab, but it is only a 30% dose of Ofatumumab that we trial participants are given for that occasion, since it represents only the first day of the trial. Then, on all of the other days of the first 28-day cycle just past, I was given either a full dose of Methylprednisone or a full dose of Ofatumumab, but not both on the same day.

So, perhaps it was just due to the heavy dosage load today, but I felt a bit more "beaten up" by the time we left D-F than usual - nothing unbearable (and certainly nothing to be worth juggling dosages for), but I did have a very "heavy head" feeling, and my vision seemed somewhat "foggy" (not out of focus, but just subdued in color and with low contrast), and, overall, I felt as if I weighed about 400 pounds (more than a bit over my actual weight - <g>), and I felt as if I was moving through molasses (well, maybe more like 50-W diesel motor oil, but that may not mean so much to everyone, so "molasses" it is).

Then, for the blood test results after the fourth week of testing, there was also a bit of a disappointment, in that the white cell counts (including the differential lymphocyte count) did indeed go down once again, but not by all that very much this time, making for a shallower slope for the curves on the total white cell graph and the lymphocyte graph - still in the right direction, but not so determinedly so. (Maybe I'd been "spoiled" so far.) Bummer...

On the other hand, my platelet count continues to rise, and this indicates that my bone marrow is definitely still improving - i.e., it is still being cleared of excessive lymphocyte stem cells, and of their excess new and immature offspring. :-)

We still do have to go back to Dana-Farber on tomorrow and Friday this week - each day for a full dose of Methylprednisone, preceded by a half-dose of Benadryl (but with no Ofatumumab on either day). I'll have more to say about all of this in my next post, probably sometime after Friday's trip to D-F (i.e., probably later on Friday, in the afternoon or evening).

There will be graphs.

Please stay tuned...

Categories: Leukemia

A Trade or Two

Posted by Frederick Wasti
Apr 15 2012

A stem cell transplant (an "SCT") represents a trade - or, actually, I guess it may represent two trades, as follows:

In one sense, if I were to submit to an SCT procedure, I would be trading in my own immune system, in return for the immune system belonging to some unknown matched donor. The success of an SCT would require that my own immune system be disabled, in order that my body would not reject the donor's stem cells given to me. This would necessitate a few days of chemotherapy just before I would be given the transplanted cells. (Dana-Farber happens to generally use the drugs Fludarabine and Bisulfan for this, and, interestingly, each of the major SCT centers uses a somewhat different "cocktail" for the purpose).

Upon the introduction of the foreign donor cells to my body, a battle would then ensue - my own immune system cells would try to destroy what they would detect as "invaders", while the donor immune system cells would attack my own cells as being "foreign" to them. In an ironic twist, I would then likely be rooting for the donor blood cells to win and for my own blood cells to lose - if my own cells did succeed in destroying the donor cells, the transplant would end up failing (and that's why the Fludarabine and Bisulfan are used - to "stun" my immune system into not responding to the invaders, so that the invaders might not be rejected).

However, if my own immune system's cells remain passive after I am given the donor cells, the donor cells would hopefully succeed in destroying their competitors (i.e., my own blood cells, but, most importantly, my aberrant leukemia cells, too), and they would proceed to make my body their new home. So, I would have ended up trading in my own immune system for someone else's. Well, that represents trade number one.

Now, in order to explain the second trade, I will first have to try to explain a couple of new terms (well, they may or may not be new to you, but I can certainly say they are somewhat new to me):

First, there is something called the "Graft versus Leukemia" (or "GVL") effect to consider. This is the reason why stem cell transplants are performed on people having leukemia. Remember that the main problem in leukemia is that an increasingly larger and larger number of leukemic white blood cells (that started out as just one cell that mutated and then started reproducing uncontrollably) are "accepted" by the rest of the cells in the body (or, in the case of CLL, the aberrant lymphocytes can also "hide out" in safety in the spleen and the lymph nodes). That is to say that the leukemia victim's own body does not adequately defend itself against the cancerous blood cells within - the cancerous cells are (most of the time) able to avoid detection as being as dangerous as they are by the immune system.

However, as a result of a successful SCT, the donor cells "grafted" into a new body do not feel so "kindly" toward the leukemic white cells (or to any of the other white cells, either - that was trade number one, you may remember) - in fact, the donor cells will try to destroy all the leukemia cells, and this particular positive effect is where the name "Graft versus Leukemia effect" comes from. It should be obvious that ~this~ would represent the hopeful outcome from a successful SCT.

But, there is also something referred to as "Graft versus Host Disease" (or "GVHD") to consider as well. The same donor cells that would now be busily judging leukemia cells to be fully deserving of being destroyed will also tend to find the rest of the host's body cells to be at least somewhat foreign, too, and may cause problems if they try to reject their host (even though it is now their home, but they may seem not to "know" that). The resulting GVHD might be chronic in nature (resulting in such things as skin inflammation, gastrointestinal tract irritation, etc.), or it could even be acute.

The nature of the match between the host blood cells and the donor cells is important, but - perhaps surprisingly, until one thinks about it - the match must ~not~ be "too good":

It should be clear that, if the match were to be poor, the damage done by the host cells to the donor cells (even though the host cells have been "stunned") could result in rejection of the transplant. Or, the opposite could occur - the donor cells might wreak havoc on many of the cells in the host body (acute GVHD). Obviously the match should ideally be close enough that neither of these events occur.

However, the match between host and donor cells ~cannot~ be "too close", either. If one thinks about it, a "perfect match" (such as would occur if the transplant occurred between two genetically identical twins), would make the transplant ineffective. If the host's own immune system had been "tolerating" aberrant leukemia cells for some time already, then genetically identical donor cells would likely also be just as "tolerant" - in this event there would ~not~ be any Graft versus Leukemia effect at all, causing a seemingly successful transplant (i.e., one that was not rejected, and did not cause any GVHD to occur, either) to be essentially ~useless~, since no leukemic cells would end up being destroyed.

So, there has to be a balance - the match between donor cells and host cells must be close, but not too close - there has to be a compromise between GVHD and GVL. In other words, a successful SCT would take away leukemia, but it would also replace it with another disease - Graft versus Host Disease. And that is trade number two - the patient in a successful transplant trades in their leukemia for a hopefully more manageable disease, GVHD.

Sometimes life can indeed be a compromise... :-)

[Please note - I have not been talked into having a stem cell transplant yet - the above is just the result of having to think about it and research about it.]

Categories: Leukemia

Stem Cell Transplant ?

Posted by Frederick Wasti
Apr 14 2012

I am having a bit of difficulty composing this blog entry, so please bear with me...

After my infusions on Wednesday, Diane and I had a couple of meetings, one with Dr. Vincent Ho and one with Irene Heffernan (a nurse), both of the Dana-Farber stem cell transplant program, and then I also agreed to have a few vials of blood drawn for starting a preliminary transplant donor match search. (I have not yet agreed to initiate a formal donor match search, which is a lengthy, involved procedure, and which would require a formal commitment on my part before it would take place.)

The facts:

There is no fully successful chemical treatment for CLL - that is to say that there is no chemotherapy for CLL that could ever result in a cure. The only means to ever possibly achieve an actual cure is to undergo a successful stem cell transplant procedure. It is virtually impossible to kill off all of the aberrant lymphocytes in CLL, so that any ~apparent~ remission is always only temporary, as the relentless CLL cells ~always~ eventually return in number after chemotherapy. (Yes, I already knew this.)

The only possible ~true~ cure for CLL is to destroy a patient's own immune system, and to replace it with stem cells from a healthy well-matched donor, cells that would take over as the new immune system for the benefit of the adopting host. However, there are risks and trade offs involved in any stem cell transplant procedure, making the choice between chemical therapy and a stem cell transplant not a simple one to make at all. (I already knew all this as well.)

Dr. Ho did explain why a stem cell transplant can be advantageous, especially for CLL patients such as me (I have poor prognostic indicators, which predict rapid progression - that much I already knew), and that it might be best to soon transition from the clinical trial to a stem cell transplant procedure at such time as might be optimum. Although stem cell transplants are not generally recommended for early CLL treatment in most patients, someone with my prognostic indicators is unlikely to have as deep a remission with any follow up chemotherapy as with the first one, so transplants are indeed now being recommended as part of first-time treatment for people such as myself. (I had learned from my "regular" D-F doctor, David Fisher, of this shift in strategy only recently.)

Because of the time that it takes to carry out a search for a suitable donor, it is now advisable for me, according to Dr. Ho, to decide very soon to pursue a stem cell transplant procedure, if I am to have the highest chance of success with one, due to (hopefully) being in as deep a remission as possible at the time of transplantation, without waiting until the leukemia cells return in number later on. (This is a somewhat novel concept to me, one which I had thought of only obliquely before now.)

The bottom line is that Dr. Ho would recommend deciding within the next couple of weeks to have a stem cell transplant. I am stunned. It is not the idea of having a stem cell transplant that is most difficult to accept - it is the thought of having to decide for or against a transplant on such short notice that is so unsettling, at least it seems so at this moment.

So, I have been spending a lot of time over the last couple of days researching scientific literature online (trying to learn as much as I can about the ramifications of a transplant procedure), but I may also have been guilty of trying to put off writing this post, too, since I still really didn't know quite what to say or how to say it very well. Perhaps I could delete all of this and start over again, but I think I'd also end up feeling like deleting any second attempt as well. And so, maybe I should just let this go for now. (?)

I will have more to say about this in upcoming posts...

Categories: Leukemia

Week Four

Posted by Frederick Wasti
Apr 11 2012

Today (Wednesday, 4/11/12) was Week Four's long day at Dana-Farber for another round of Ofatumumab. All in all, the infusion of a small dose of Methylprednisone, followed by a bit of Benadryl, followed by a full dose of Ofatumumab, all went pretty routinely, which is, of course, all good news. But today's ~really~ good news was the blood test results, which I received mid-morning, from the blood drawn from me first thing this morning.

Once again, another week of treatment (and today's blood test results represent the blood counts after three weeks of treatment) caused my blood to continue the reversal of its (until recently) fairly steady upward progression. Let's take a look at how the total white cell count has changed over the past several weeks at D-F (starting shortly before my treatment commenced):

Looking at the above graph shows that my white blood cells have continued to decline in number, and have gone from being counted in the upper fifties (per microliter) down to the upper teens.

To put this change (which is certainly in the ~right~ direction) into some perspective, here is a graph of my white counts from the time of diagnosis until today:

Notice that, after "only" (<g>) three weeks of treatment, my white cell count is already lower than it was around the time of my first diagnosis of CLL.

To get an even "longer view" of how the decline fit's into "the big picture", notice in the following graph that, while the count is still not down to below 10,000 (as it was for a long time until CLL caused my white count to start to rise):

OK, just one more graph for today: The above three graphs show the change in total white cell quantity over different time periods, but the medications I am taking are not (or should not be) destroying other than lymphocytes (and you already know that is where the middle "L" in "CLL" comes from, right?), so let's take a look at the absolute lymphocyte count (not as a percentage of the total white cell population, but as an actual number of cells per microliter):

Not too shabby, eh ?!? :-)

However, the final events of today, which are still sinking into my brain, and which will cause a lot of thought and research over the next couple of weeks, were two separate meetings, with one of the doctors and with one of the nurses involved in the D-F bone marrow transplant program, and then having several vials of blood drawn to start a preliminary transplant donor match search. I will have much to say about this in (I am sure, more than a couple of) future posts...

Categories: Leukemia

Fred Cells 102

Posted by Frederick Wasti
Apr 07 2012

In my earlier "Blood Cells 101" entry (from 4/1/12), I tried to give a "Cliff's Notes" version of what blood cells are supposed to be like in normal blood. Then, in my "Fred Cells 101" entry (from 4/3/12), I tried to provide a description of what has been happening to my total white cell count over time. In this post I will try to describe what has been going on with some of my individual types of blood cells over time, at least from diagnosis to the start of treatment. (In later posts I'll take a look at what is happening to them after treatment has begun.)

First, let's take a look at the name of my type of leukemia - it's called "Chronic Lymphocytic Leukemia", or "CLL" for short. Starting at the end and working backwards, the term "Leukemia" (from the Greek words "leukos" for "white" and "haima" for "blood") indicates that CLL is a condition where white blood cells are in excess. The term "Lymphocytic" indicates that the specific culprits are lymphocytes. Finally, the term "Chronic" suggests that (at least for many affected people) the condition can be slow in growing or even indolent, in contrast to being "acute" (or rapidly progressing, as it actually can be in others).

So, since CLL is a cancerous disease involving the lymphocytes, let's take a look at my lymphocyte counts over time:

At first glance, it seems as if "not too much" has been happening to my lymphocytes - that is to say that the trend is indeed an upward trend, but, just from "eyeballing it", the rise doesn't seem to be "overly dramatic". However, please remember that the above graph, and each of the other graphs included in this particular entry, are from the time of diagnosis until the start of treatment (i.e., my "Watch and Wait" period), but the condition had already progressed quite a bit before it was "accidentally diagnosed" from an MRI scan of my arthritic left hip showing enlarged lymph nodes).

If you think back to (or look back at) my "Blood Cells 101" post, you should note that lymphocytes are supposed to be common in blood, but not overly common - that is, the portion of white blood cells that are lymphocytes is supposed to be about 30% or so. Therefore, at the time of my diagnosis, rather than having about one-third of my white cells being lymphocytes, I already had a much larger percentage of lymphocytes present.

One reason why the above graph does not seem to be "overly dramatic" is that, while the lymphocytes have indeed been increasing in number for some time, the total number of white cells - the total leukocytes - has also been increasing. Let's take a look at what the actual ~number~ of lymphocytes has been like (and not just their proportion) over the same period of time:

Perhaps this second graph better shows that, indeed, my lymphocytes have been increasing rather significantly over time. (The numbers on the vertical axis represent the actual number of lymphocytes, in thousands, per cubic millimeter or per microliter of blood.) Keeping in mind that the normal number of all leukocytes in blood is supposed to be about 5,000 to 10,000 per microliter, and that approximately 30% of that number range should normally be lymphocytes, it follows that the normal number of lymphocytes per microliter should be, say, about 2,000 to 3,000. Clearly, at the time of diagnosis, my absolute lymphocyte count was considerably higher than that, in the "teens" of thousands per microliter, and rising over the next year-and-a-half into the forties.

But, exactly what is the problem with this? Why is it so bad to have too many lymphocytes? (After all, don't lymphocytes do good things?) There are several problems with too many of any one type of blood cell, but let's just consider one right now: The excessively high rate of production often means that the bone marrow, responsible for creating all of the types of blood cells, can become so crowded with reproducing aberrant cells that the production of other cell types can slow down and could ultimately virtually stop. Therefore, the number of other cell types (the red cells, other white cells, and/or the platelets) can also start falling, even as the number of aberrant cells is rising so fast that the total white cell count is increasing.

Here is a graph of how my neutrophils have fared during the time in question here:

Not surprisingly, it can be seen that the neutrophil percentage has been dropping at the same time that the lymphocyte percentage has been rising. The absolute neutrophil count (in thousands of cells per microliter) can also be shown to have been falling:

However, it is not just the rate at which the neutrophils seem to have been dropping during this time period that is troubling. Back in "Blood Cells 101" it was pointed out that, in normal blood, neutrophils should be the most numerous leukocyte type (while lymphocytes should be the second most numerous) - there should be about twice as many neutrophils as lymphocytes. It is clear from the above graphs that this has been turned quite upside down - my lymphocytes have easily become the most numerous white cells in my blood, and the proportion of neutrophils has suffered significantly as a result.

Furthermore, it is not so much the proportion of neutrophils that is troubling - the absolute number of neutrophils that have survived my CLL has declined as well. Keeping in mind that neutrophils are supposed to be well over one-half of the white cells in number, there should be perhaps 4,000 or 5,000 in every microliter of blood, and not 1,000 or 2,000. Considering that neutrophils play a very important role in immunity (especially for protection against bacteria and fungi), it should be clear that a declining neutrophil count is ~not~ good news.

I'll take a look at how red blood cells and platelets have been faring in an upcoming entry - please stay tuned for "Fred Blood 103" - <g>.

Categories: Leukemia

Week Three

Posted by Frederick Wasti
Apr 05 2012

On Wednesday I went to Dana-Farber for another round of Ofatumumab. It does seem as if the pattern for ~most~ Wednesdays (i.e., each Wednesday that is ~not~ part of the first week of each 28-day cycle) will be approximately as follows:

1. An intravenous line will be established into a suitable vein on one of my hands or arms. (The term "established" is a euphemism for "poked" - <g>.) (The term "suitable" is a bit of a euphemism, too - I really do have crummy surface veins, and getting a line "established" can be a bit of a challenge sometimes - <g>.)

2. A couple of tubes of blood will be drawn immediately and sent to the lab for testing. (It seems that I will likely find out some of the blood test results later in the morning, which is very nice, especially if there are any "good numbers" to be gleaned from the lab results.)

3. I will be given two 500 mg Tylenol/Acetaminophen tablets (I don't know for what - considering what they are doing to me each time I visit there, I can't see how much good two Tylenol tabs could do - <g>) (OK, OK, I guess I have to assume that they're somehow useful for helping prepare me for the Ofatumumab - <g>).

4. I will be given a 50 mg intravenous dose of Methylprednisone, to help prepare me for the upcoming Ofatumumab. (This is quite a different dose from the much larger dose - 2,350 mg - of Methylprednisone that I receive on each of the three days of each first week of each 28-day cycle).

5. I will be given a 25 mg intravenous dose of Benadryl, to help prepare me for the upcoming Ofatumumab. (Previously, I was given 50 mg doses for this purpose, but, since I seem to be tolerating the Ofatumumab so well, the amount of groggy-inducing Benadryl has been mercifully cut back.)

6 And then - finally - I will be given my 1,000 mg dose of Ofatumumab (in 1,000 ml of saline solution). This represents the longest portion of the day at D-F, although the rate of infusion has been "upped" each time I've received it so far, so that this Wednesday did not take as long as last Wednesday as a result.

I mentioned that I do receive some "feedback" in the form of blood test results sometime each Wednesday morning from the blood drawn earlier that morning. (The results may not always be complete due to the time needed to obtain all the results - therefore, the differential results for each individual white blood cell type might be missing, although the total white cell count, the red count, and the platelet count will likely be provided.)

There is some good news: Simply looking at the total white cell count, a couple weeks of Methylprednisone and Ofatumumab have started to turn things around - please note the following graph:

I have emphasized the most recent tests done at D-F for the above graph. March 6th was the day I met with Dr. Fisher at D-F to discuss my treatment options (ultimately deciding for this clinical trial); March 14th was my "screening day", when I qualified for admission into the trial; March 21st was the first day of the trial itself (with the blood being taken for testing before I actually started the treatment); March 28th was during the second week of treatment (showing the results of one week of treatment); and April 4th was from the third week of treatment (showing results from two weeks of treatment).

It can be readily seen that, before treatment started, my white cell count was pretty consistently in the upper fifties (although likely rising slightly each time). However, after one week of treatment, the white count had dropped from the fifties into the upper thirties, and then it dropped even further, to the upper twenties, after a second week of treatment. What's ~not~ to like about that? (<g>)

Of course, there are other blood parameters to consider, too, but the above results do represent an immediate improvement in my blood, and receiving feedback such as this is indeed gratifying. The battle is still being fought (and, in fact, there is still a long road to travel yet), but the numbers are starting to move in the right direction. And so, I ask again, what's ~not~ to like? (<g>)

Categories: Leukemia

Fred Cells 101

Posted by Frederick Wasti
Apr 03 2012

In my preceding "Blood Cells 101" entry of 4/1/12, I tried to give a "thumbnail sketch" of basic information about blood cells. In this entry I will try to take a look at what has been going on with my total white blood cell numbers up to 3/21/12 (just before my first clinical trial treatment began). [I will do the same for the numbers of individual white cell types and related parameters in other posts, and I will also take a look at how these numbers will have changed (hopefully all for the better - <g>) as a result of treatment in other upcoming posts as well.]

In CLL, the type of leukemia I have, treatment is not generally started as soon as diagnosis has been made. (It has been shown statistically that early intervention does not lead to longer symptom-free survival or to longer life.) Instead, a period of "Watchful Waiting" or "Watch and Wait" (or maybe "Watch and Worry" - <g>) begins, where blood tests and checks for symptoms are made on a regular basis (in my case about every three months or so) to see just when it would be prudent to actually start treatment.

So, let's take a look at my total white blood cell counts since diagnosis in mid-July of 2010:

Time is on the horizontal axis and the total number of white blood cells in thousands of cells per cubic millimeter (or per microliter) is on the vertical axis. The little red diamonds represent the blood tests that I've had during this time period. The blue line is a smoothed curve connecting the "dots" (the little red diamonds), while the "less wiggly" black line is a trendline. (This graph and others that will follow have been generated using Microsoft Excel.)

It should be seen in the above graph that my total number of white cells remained fairly stable for almost a year (hovering in the twenties and thirties), but during the last half-year or so the number has definitely started increasing, reaching the fifties fairly recently.

If you waded through "Blood Cells 101", you might remember that the normal number of white cells per cubic millimeter of blood is supposed to be between about 5,000 and 10,000 or so. Obviously then, at diagnosis I was already well above that range. This is not unusual, however. Many people with leukemia find out first from an "accidental diagnosis", so to speak - that is to say that initial suspicion of leukemia might result from some other test or symptom instead. In my case, the first inkling I had of possible leukemia came from an MRI scan in June of 2010, where the radiologist who read my scan found "abnormal lymphadenopathy in the visualized portion of the left iliac chain", or, in other words, enlarged lymph nodes in part of my lower left abdomen. (The MRI, by the way, focused on my hip left joint, which ended up being replaced with an artificial hip joint in May of 2011.)

As a result of finding enlarged lymph nodes, my primary care physician, Dr. Thomas Browning, suspecting the possibility of leukemia, ordered blood tests performed, and referred me to Dr. Hannah Yamin, a hematologist/oncologist at the Cancer Center at Jordan Hospital in Plymouth. Dr. Yamin had additional blood tests performed, with the diagnosis of CLL being confirmed. [Bummer.]

But, what were my white blood cell counts previous to diagnosis? After all, presumably I once had normal white cell numbers, before the numbers had started to rise. So, I went back and found all of the blood test results I could lay my hands on, and generated the following graph:

It can be seen that my total white cell counts were fairly normal for a long time, and as recently as 2008, but probably started to rise during 2009. I don't have any white cell numbers from 2009, as shown by the sizable gap between the red diamonds (the "dots") and the fairly long straight line during that time period - I did have one blood test during February of 2009, but it was for metabolic parameters, lipids, and a PSA screening, not for blood cell counts. (However, even if I did have a cell count made during 2009, which likely would have shown a somewhat elevated white count, don't forget that it would ~not~ have resulted in earlier treatment - it probably would have resulted only in an earlier diagnosis and a longer "Watch and Worry" period.)

I should point out that having a white blood cell count above 10,000 is not, by definition, necessarily leukemia. Rather, leukocyte counts above 10,000 or so are referred to as "leukocytosis", and can result from a number of other factors besides leukemia, such as infection. (Similarly, counts below 5,000 are referred to as "leukopenia".) Nonetheless, there are a number of blood test results, and anatomical and physiological parameters, that can specifically point to leukemia, and to which type of leukemia is involved, and I will try to cover some of them in other future posts. Please stay tuned for "Fred Cells 102" - <g>.

Categories: Leukemia

Blood Cells 101

Posted by Frederick Wasti
Apr 01 2012

Blood Cells

For anyone interested in knowing something about blood cells (something of considerable interest to me, especially over the last year-and-a-half - <g>), here is Fred's "Reader's Digest" treatise on 'em. (Please note that the numbers I've provided below are only approximate values, just to try to keep things simple, and that they can and do vary somewhat from my stated "typical" values, even in a person with "normal" blood.)

[I have tried to keep this as brief as possible, limiting it to ten main points, and the last three are included here primarily for completeness, so, if you're looking for the easiest way out of this blog entry (<g>), please just try to pay attention to the first seven points.] [And there'll be no pop quiz, either...]

1. Blood is made up of a liquid component (plasma, about 55% of the blood volume) and a solid component (blood cells, or corpuscles, about 45% of the blood volume).

2. There are three main types of blood cells - red blood cells (or erythrocytes, filled with hemoglobin, for transporting oxygen and carbon dioxide), white blood cells (or leukocytes, which protect against infections and foreign substances), and platelets (or thrombocytes, which help in blood clotting).

3. Blood cells are generally manufactured in bone marrow tissue, with the rate of production of each usually properly regulated by the body to replace the cells that die (but the rate can increase or decrease as a response to various conditions).

4. Red blood cells normally make up over 99% of the cells in blood, and there normally are about 5,000,000 or so per cubic millimeter. White blood cells are of approximately the same general size range as the far more numerous red cells, but there are normally "only" about 5,000 to 10,000 per cubic millimeter, Platelets are much smaller than either red or white cells, and are intermediate in quantity, there being typically about 300,000 per cubic millimeter.

5. Since leukemia involves certain of the white cells running amok (although leukemia can indeed affect red cells and platelets), let's take a closer look at the five main types of white blood cells or leukocytes (which, by the way, are found not only in the blood, but can also be found in lymph and in body tissues).

6. Neutrophils normally make up about 60% of the white cells, and therefore are easily the most numerous leukocytes. Neutrophils engulf and destroy pathogens (especially bacteria and fungi) and debris.

7. Lymphocytes normally make up about 30% of the white cells, and therefore are generally the second most numerous leukocytes. Lymphocytes, common in both the blood and in lymph tissues (and, unlike all the other blood cells, manufactured not just in bone marrow but also in the lymph tissues), are themselves of several types, but, as an example of one type of lymphocyte, B-lymphocytes are involved with labeling (or "tagging") the surface of foreign invaders and foreign proteins with chemicals called antibodies. (Since lymphocytes are the type of aberrant white cell involved in my type of leukemia, I will certainly have more to say about them later.)

8. Monocytes normally make up about 6% of the white cells. Monocytes engulf and destroy pathogens and debris, especially in body tissues.

9. Eosinophils normally make up about 3% of the white cells. Eosinophils help destroy pathogens (such as larger parasites) and foreign debris that have been marked with antibodies by B-lymphocytes.

10. Basophils normally make up about 1% of the white cells, and therefore are generally the least numerous of the leukocytes. Basophils release histamine into damaged body tissues in order to stimulate inflammation.

I know that the above may be a lot to digest at once, but you can always come back to this and look at it again. Perhaps, though, better than that would be to check other online sources of information - a good source (including excellent pictures) is at http://www.funsci.com/fun3_en/blood/blood.htm

Categories: Leukemia