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And May Their Paths Never Cross Again

Posted by Frederick Wasti
May 30 2012

Today was "just another ol' Ofatumumab day at Dana-Farber". Things went pretty smoothly, except: Because of the Memorial Day weekend (and the larger than usual number of patients being serviced today), the wait to get an intravenous line started and to have my blood drawn was longer than usual, and therefore the time my blood test results came back, so that Dr. Fisher could check them and provide the orders for the day, was later than usual. So, we probably ended up spending an hour and a half longer at D-F than we did last week. Oh well...

The good news is that the blood test results showed even more improvement - that is to say my lymphocytes continued to decline, so that the proportion of lymphocytes compared to neutrophils could continue to improve. Let's go to the graphs:

Here is the latest graph showing my lymphocyte proportion of the total white cell count:

And here is the corresponding graph for the neutrophil proportion:

Last week's "mirror image" situation continues, with a milestone of sorts having been reached sometime during this past week. On the previous Wednesday, the lymphocytes had dropped to 48% while the neutrophils had risen to 45%. However, today, the lymphocytes have fallen to 35% and the neutrophils have risen to 56%. This milestone would have been reached at the exact moment, sometime during the past week, when the neutrophils actually surpassed the lymphocytes for the first time in several years. (Don't forget that, in normal blood, neutrophils ~should~ be approximately twice as numerous as lymphocytes, yet, in my blood, lymphocytes have been far more numerous for quite some time now, since well before diagnosis.)

Despite the mirror images that the above two graphs form, though, the changes in proportion over time have mostly been due to the large increase in ~lymphocytes~ over a number of years, followed by a recent rapid decline due to treatment.

Let's look at the absolute number of lymphocytes (in thousands of cells per microliter) since diagnosis:

Now let's compare the absolute number of neutrophils over the same time period:

The lymphocyte numbers can be seen to have changed quite dramatically, while, at first glance, the trends in the neutrophil count may seem a bit less obvious.

The lymphocytes had been on a fairly steady march upward from diagnosis to treatment, and then (quite fortunately) went into a rapid decline. In contrast, the neutrophils, several years ago (before CLL started to rear its ugly head), certainly must have been the most numerous of my white blood cell types, but, due to leukemic lymphocytes crowding them out, they did decline over time until treatment started (and, in fact, they had declined so much by this past February, that the low neutrophil count was a major factor pointing to the need for treatment).

Still, if one looks carefully at the absolute neutrophil graph, it does show that the neutrophils have indeed bounced back once treatment began, even if the graph appears to be a bit on the "jagged" side. However, as I see it, the neutrophils may simply be coming along just as fast as they can, considering that they may be doing so against some difficulty, also related to the treatment:

You see, the good news for the neutrophils is that the Ofatumumab has been attacking the competing lymphocytes, as has the Methylprednisolone. However, while Ofatumumab targets only lymphocytes, Methylprednisolone is not nearly as specific, and it destroys all sorts of white cells, including, of course, some of the neutrophils. So, the greatest change so far, at least in Part A of the clinical trial, has been in the population of lymphocytes, while the numerical change in the neutrophils, while gratifying, has been smaller (but still significant - I am at less risk now of ~bacterial~ infections than I was before treatment started).

OK, just one more graph - I did combine the percent data for both lymphocytes (red curve) and neutrophils (blue curve):

Here the "mirror images effect" can be seen pretty easily, but the best part of the graph is shown way over to the right, where it can be seen that the two curves, going in opposite directions, had actually crossed paths sometime this past week. (And, "May Their Paths Never Cross Again"...) (<smile>)

Categories: Leukemia

Methylprednisolone and Me, a Love/Hate Relationship (#1)

Posted by Frederick Wasti
May 28 2012

Yes, I did spell this entry's title correctly - "Methylprednis-OL-one", and not "Methylprednisone". Technically, these two names belong to two molecules very slightly different from each other, and it is Methylprednisolone that I'm being given at my Dana-Farber trial, even though, up to now, I've tended to use the slightly easier to say and slightly faster to type "Methylprednisone" in this blog. (In fact, I just Googled "methylprednisone site:leukos.us" and "methylprednisolone site:leukos.us", to learn that I've used the shorter name perhaps a dozen times, and the longer name just once, and the latter was just as part of a quotation.)

(And, speaking of the title, "Methylprednisolone and Me, a Love/Hate Relationship", yes, I do know that, grammatically, it should really be "Methylprednisolone and ~I~", but "Methylprednisolone and Me" is so much more alliterative - <grin>.) (And, yes, "Methylprednisone and Me" is easier to say than is "Methylprednisolone and Me", but I'm going to use the correct name from now on.)

Interestingly, one can use Google to prove that there is some popular confusion over whether Methylprednisone and Methylprednisolone are the same chemical or not. If you were to Google "Methylprednisone Methylprednisolone", you would get some search hits that state that "methylprednisone is a common misspelling of methylprednisolone" (and the Google results page would even ask you, "Did you mean: Methylprednisolone Methylprednisolone" (see the image above), as if you had spelled Methylprednisolone incorrectly, and as if you had ~really~ meant to type the exact same word ~twice~ in a row - <grin>).

However, your Google search would also produce hits that lead to scientific papers about "analysis of methylprednisolone and methylprednisone", and "bioavailability and nonlinear disposition of methylprednisolone and methylprednisone", and "interconversion of methylprednisolone and methylprednisone", all of which would suggest that the two words are not merely names for the same molecule, but are names for two different molecules (even if they are closely related, as the phrase "interconversion of methylprednisolone and methylprednisone" might suggest).

Also interestingly, even the clinical trial I am participating in, "Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL", uses "Methylprednisone" once, in the trial's title, but then uses "Methylprednisolone" within the trial's description about a dozen times.

However, they ~are~ indeed different molecules - Methylprednisone has a molecular formula of C22 H28 O5 while, for Methylprednisolone, it is C22 H30 O5.

But I digress...

Today I am going to use the proper name of "Methylprednisolone", and I will note that this should, at least partly, be out of respect, because that is the name of one of the drugs that is helping to save my life (or at least helping to extend it a bit).

Let me try to explain what Methylprednisolone is, and then why it should be helping me:

First, I would like to point out that, yes, Methylprednisolone is a steroid, but it is not one of "those" steroids. That is to say, the steroids I will be discussing here are known as glucocorticoids and mineralocorticoids, and have nothing to do with the anabolic steroids as used by some athletes.

The terms "glucocorticoid" and "mineralocorticoid" are used for several different steroid hormones naturally produced by the cortex (i.e., the outer layer) of the adrenal glands. In the picture below you can see where the adrenals are located (and also ~why~ they are so named - "adrenal" comes from the Latin words "ad", meaning "near", and "ren" meaning "kidney"):

There are two layers of glandular tissue in each adrenal gland - there is an inner medulla area and an outer cortex area. The medulla secretes Adrenaline (a.k.a. Epinephrine) and Noradrenaline (a.k.a. Norepinephrine). The cortex secretes a number of hormones, of which Aldosterone and Hydrocortisone (a.k.a. Cortisol) are a couple of examples.

[Please note that I am going to use a few images of structural formulas below. Please try to avoid getting bogged down in their details, but instead just please notice that their structures show an interesting similarity, but that they also show differences that are related to how they each differ in function.] [An apology (sort of): Having been a science person and science educator for most of my adult life, and, most specifically, having taught Human Anatomy and Physiology at both the high school and college levels for a couple of decades late last century, it is difficult for me to spend many hours now each week being pumped full of chemicals without me also thinking a lot about those chemicals.] [<grin>]

Aldosterone (above) is the principal mineralocorticoid hormone - it controls water and mineral balance in the body. (The term "mineralocorticoid" denotes that Aldosterone is a sterOID produced by the adrenal CORTex that affects MINERALs.)

Hydrocortisone (above) is one of several glucocorticoids secreted by the adrenal cortex, and is a hormone that has a variety of important functions throughout the body:

Metabolic functions of Hydrocortisone, which do affect ~every~ single individual cell in the body, include the buildup and breakdown of food molecules, including fats, sugars, and amino acids. Among other things, Hydrocortisone tends to counteract insulin - while insulin decreases the level of glucose in the blood and increases glucose within body cells, Hydrocortisone does the opposite. (The term "glucocorticoid" is used for hormones such as Hydrocortisone, which are sterOIDs produced by the adrenal CORTex that affect GLUCOse utilization.)

Important immunological functions of Hydrocortisone include regulating the number and functioning of certain white blood cells and the control of inflammation throughout the body. There are many (perhaps dozens of) other functions for Hydrocortisone, too many to mention here (and I'm betting that you're probably glad of that - <grin>).

And that brings me back to Methylprednisolone:

Methylprednisolone is a synthetic glucocorticoid that acts just like Hydrocortisone, except that it is more powerful and more long-lasting in its effects: Compared to Hydrocortisone, Methylprednisone is 5 to 7.5 times more potent, gram per gram. And then, while the half-life of Hydrocortisone (the length of time that one-half of the original dose is still active in the body) is 8 hours, the half-life of Methylprednisolone is between 18 and 40 hours.

So, in my clinical trial, I am being given HDMP (high-dose Methylprednisolone), or, as can be seen above, high doses of what might be called "Super-hydrocortisone". (And I also receive small doses of Methylprednisolone before receiving Ofatumumab.) Not surprisingly, Methylprednisolone has had (and is having) significant effects on my body, some of them good (of course - else why would I be taking it? - <grin>), and some not so good. I'll discuss these effects (both the intended benefits and the "collateral damage" side effects) soon...

[By the way, if you're at all curious about the structural relationships between the various cortical steroid molecules, there's an excellent graphic of this on Wikipedia at This Link.]

Categories: Leukemia

Mirror Images

Posted by Frederick Wasti
May 23 2012

Today was "just another typical Ofatumumab infusion day" at Dana-Farber. (Last week, Week 1 of Cycle 3, I had the "full Methylprednisone and Ofatumumab treatment".) Overall, things went relatively routinely.

The only time today when the situation was not as I was expecting (or hoping) was when I had my first look at the results from this morning's blood tests. I was hoping, of course, for a continued drop in the total white cell count, and that was the number I looked for first. However, I was immediately a bit disappointed to find that, rather than being below 10% (as it had been over the past two weeks), it had now gone up to 13.3%. (I did have a couple weeks of plateau a few weeks ago, but ~this~ was not just a plateau, but a distinct rise.) At that moment, telling myself that "well, the total white count can't keep marching to zero, and it maybe has to start leveling off sometime soon anyway" seemed to offer only a small consolation.

So here's the total lymphocyte graph, including data from just before the clinical trial started until today:

As you can see, there was a bit of an upturn over this past week, although admittedly it was not huge (even if somewhat unsettling).

However, after settling down and looking at some of the other numbers, I started to realize that there were some interestingly good numbers staring back at me. Please let me try to explain.

Perhaps you may remember wading through my "Blood Cells 101" entry (April 1st) and my "Fred Cells 101" and "Fred Cells 102" entries (April 3rd and 7th). (Or perhaps you were "lucky" enough to avoid them - <g>.) Well, you don't have to go looking back at them, because I'm going to provide you with the relevant numbers you need right here - <g>:

In normal blood, the percentage of the most common of the white blood cells, the neutrophils, is supposed to be about 60% or so, and the percentage of the next most common white cells, the lymphocytes, about 30% or so. However, back around the time of my CLL diagnosis, my neutrophil counts were down in the 10% to 15% range, and my mostly leukemic lymphocytes (which were responsible for crowding out the neutrophils) had counts up in the 70% to 80% range. The situation was, at that time, worse than upside down. Well, let's take a look at how the neutrophil and lymphocyte counts have changed since.

First, here's a graph of the lymphocyte percentage since the time of diagnosis:

And here is a graph of the neutrophil percentage over the same period of time:

I would like you to notice a few significant points:

1. At the time of diagnosis, the lymphocytes were much too high and the neutrophils were much too low.

2. During my "watchful waiting" period (from the time of diagnosis to the start of treatment), the situation did gradually get worse.

3. However, once treatment had started, the percentage of lymphocytes rapidly went down, while the percentage of neutrophils did rapidly increase.

4. Furthermore, the percentage of neutrophils is now ~almost~ as high as the percentage of lymphocytes (and, hopefully, that trend will continue until the neutrophils are significantly more numerous than the lymphocytes, as they should be).

5. Finally and interestingly (but not just coincidentally), the shape of the two curves form a pair of approximate mirror images. (That is to say that each curve looks like a corresponding vertical reflection of the other.) If you understand the significance of the two graphs, of course, you would recognize that this is the way it would have to be, as the two most numerous white cell types are competing for their share of the 100% that all the white cells have to add up to. And may the neutrophils be eventually restored to their proper prominence... :-)

Categories: Leukemia

The Father of Non-Chemotherapy

Posted by Frederick Wasti
May 22 2012

Just for the heck of it, I just Googled "Father of Chemotherapy", and the name of Dr. Paul Ehrlich (whom I first mentioned here in my May 12th blog entry) came up repeatedly in the search results. However, my premise here is that Dr. Ehrlich might not be overly happy with that appellation, at least in the sense that the term "chemotherapy" is used nowadays.

In a generic sense, Dr. Ehrlich is indeed the "Father of Chemotherapy", in that he was the first medical researcher to synthesize a specific drug tailored to fight against a specific illness. In fact, it was Dr. Ehrlich who originally coined the term "chemotherapy"! In the following image, taken from a scientific article published by Dr. Ehrlich in 1908, the term "chemotherapy" can be seen being used for the first time:

["About Modern Chemotherapy. Paper presented at the Tenth German Dermatological Society Meeting"]

However, in current modern usage, chemotherapy generally refers to the use of chemical agents to combat diseases (such as cancer), but without connoting the use of drugs that target the ~specific~ cause of a disease. That is to say there is an important distinction today between many "chemo" drugs, which affect all or most of the cells in the body, and drugs that are employed for ~targeted~ therapy.

In cancer treatment, for example, many of the traditional anticancer "chemo" drugs do their work by interfering with the DNA of reproducing cells. This makes sense, of course, because cancer cells are among those that are reproducing most rapidly. However, such drugs also affect the DNA of other cells of the body, especially those that normally also rapidly divide as well. In other words, such chemotherapy drugs would probably not represent ideal chemical agents in the mind of Paul Ehrlich, who said, when referring to using chemicals to be used against pathogens,

"We must search for magic bullets. We must strike the parasites, and the parasites only, if possible, and to do this, we must learn to aim with the chemical substances."

In other words, Dr. Ehrlich would likely have preferred chemical agents that target ~specific~ pathogens or, in the case of cancer, that target just ~specific~ cells, rather than drugs that affect all or most of the cells in the body.

["About the Current State of Chemotherapy"...]

Now, in my own situation, in the clinical trial I am involved in, I am receiving three anticancer drugs:

1. Ofatumumab attacks lymphocytes, specifically a type of lymphocyte known as B-lymphocytes. The good news is that all of the leukemic cells in my body are B-lymphocytes. (The bad news is that, while most of my B-lymphocytes are leukemic, not all of them are.)

2. Alemtuzumab (which I will receive in Part B) also attacks lymphocytes, which therefore is also good news. (The bad news is that Alemtuzumab also affects T-lymphocytes, which are not involved in CLL.)

3. Methylprednisone does target white blood cells in general, which is basically good news. (The bad news is that Methylprednisone also has profound effects on most or even all of the cells of the body.)

So, if I were somehow able to ask for Paul Ehrlich's thoughts on my chemotherapy, I think he would be at least somewhat satisfied in the specificity of the drugs. Well, he might fuss about the Methylprednisone a bit due to it not being specific enough, but I might counter that his Compound 606 was not overly specific either.

My point here is, however, that Dr. Paul Ehrlich may be known as the "Father of Chemotherapy", yet, considering the general use of the term "chemotherapy" today, he probably would have preferred to be known as the "Father of Targeted Therapy" instead.

["On the Theory and Practice of Chemotherapy"...]

(Oh, incidentally, the second most common name that came up in my Google search for "Father of Chemotherapy" was that of Dr. Sidney Farber - yes, that's the "Farber" of "Dana-Farber Cancer Institute" - who is often described as the "Father of Modern Chemotherapy" for his pioneering work for the treatment of acute lymphoblastic leukemia in children in the 1940s. And, yes, I suspect I may end up writing about Dr. Farber in a future blog entry or two...)

Categories: Leukemia

An Excellent PDF Booklet on CLL

Posted by Frederick Wasti
May 21 2012

I just noticed that the Leukemia & Lymphoma Society has updated its excellent booklet on CLL, bringing it up to date with the latest relevant information. (There are other online PDF booklets available, but I think this is still the best one out there.) So, for those who might be willing to check out just one booklet about CLL, please consider downloading and reading this one. Thanks. (Please click on the image below for the link.)

Categories: Leukemia

Part A Cycle 3 Week 1

Posted by Frederick Wasti
May 19 2012

This was Week 9 of the clinical trial, which also made it Week 1 of the third 28-day cycle of Part A, so it meant that I visited Dana-Farber for three days this week. Wednesday was (as usual) the long day, involving blood tests, Tylenol, Benadryl, high-dose Methylprednisone, and Ofatumumab, while Thursday and Friday involved basically just high-dose Methylprednisone.

I did receive the results of Wednesday morning's blood tests, and it does seem as if things continue to slightly improve. Here's how the total white blood cell count looks, from the time of diagnosis until today ("S.O.T. = start of treatment"):

 

Looking at the far right part of the curve, it still shows a mostly downward trend since the start of treatment. Recently the slope is not quite as steep as it was during the first couple weeks of treatment, but, as the bottom of the graph is now "almost in sight", that is to be expected.

For perspective, here's the graph for my known WBC count history:

I will note a couple of things at this point:

First, my total white cell count on Wednesday was the lowest it's been since perhaps the beginning of 2008.

Second, depending on whether you consider the normal WBC count range to be 5,000 to 10,000 (per microliter) (the range I usually go with), or with the even narrower (and "stingier") 6,000 to 9,000 range, my white cell count today is currently back to within the normal WBC count range for the first time in several years.

(Still, I cannot be considered to be free of leukemia. I still have an unbalance of numbers of each of the cell types, I still have proportionally too many lymphocytes, most of my too-rapidly-produced lymphocytes don't function correctly, and the vast majority of the lymphocytes I have are almost certain to still be leukemic.)

The good news is that my lymphocytes (both the bad and the good, but remember that they're most bad lymphocytes) do indeed continue to decline, as the graph below continues to show:

At this point I am over half-way through Part A of my clinical trial (the Methylprednisone and Ofatumumab part, that is) and I will be starting Part B in not too may weeks. Part B will consist primarily of more intravenous infusions of Ofatumumab and new subcutaneous injections of Alemtuzumab - the only Methylprednisone I will receive in Part B will be low doses of it before the Ofatumumab infusions, as far as I know. I believe, also, that the focus of the battle will shift slightly as well, with more cells being killed in the marrow and perhaps less so in the lymph nodes - I will have more to say about new phase of the battle later on.

Oh, and by the way, each self-administered morning injection of Fondaparinux is going well, just like the proverbial piece of cake (well, maybe a stale piece of cake... <g>).

Categories: Leukemia

Get Well Cards

Posted by Frederick Wasti
May 15 2012

I have received a number of delightful "get well" cards (and "hang in there" cards, etc.) over the last couple of months (since just before my clinical trial started), and they have ~all~ been greatly appreciated. Some of them have been personally and sensitively supportive, while some of the others are just plain funny. But humor is very helpful in keeping up morale (which, of course, is why some very thoughtful people have been sending cleverly funny cards to me).

Here's just one example - A number of weeks ago I stated in this blog:

"Another strategy for helping the kidneys during treatment is to force a lot of saline solution ('Ringer's solution') intravenously while the anti-leukemia chemicals are being infused. The result is that, although I do literally spend hours in an infusion chair when at Dana-Farber, I can vouch for the fact that I also spend part of that time trucking back and forth to and from the rest room, wheeling my infusion bags and infusion pumps behind me - <g>. (Quite an image, eh?)"

Well, here's the image on the front of one recently received card -

(<g>)

But, funny cards can be "inspirational", too - here are some of the "words of wisdom" gleaned from a small sampler of just some of them:

"On the highway of life, there are bound to be some bumps in the road..." -- "...along with crater-sized potholes, backed-up construction traffic, and that one jerk who always cuts you off. (But anyway, you'll get through it.)"

"4 out of 5 doctors want you to get well immediately." -- "That fifth one thinks you might still have a couple bucks somewhere."

"You better get well." -- "There aren't that many people I like."

"They say you learn the most from your most difficult experiences." -- "What a stupid system."

"One day, you'll look back on all this with the wisdom that distance bestows, and you'll say..." -- "Wow, that sucked."

"When life hands you lemons, make lemonade." -- "But, when life hands you a load of crap, don't make anything. Trust me on this one."

"People who think laughter is the best medicine apparently have never had morphine." -- "Take your drugs and get well."

Actually, rather than the age-old adage that "laughter is the best medicine", ~I~ like to think that "Belly Laughs are the Best Medicine".

And finally, if that image above wasn't funny enough by itself, the caption inside simply "nailed it" - <g> -

HAR !!!

Categories: Leukemia

Dr. Ehrlich's Magic Bullet

Posted by Frederick Wasti
May 12 2012

When is chemotherapy maybe not really chemotherapy? Well, the quick answer might be "when it works like a 'magic bullet' instead of like a sledgehammer". Let me try to explain what I mean by that in this entry.

I just read an article in ScienceNow (from 2006) entitled "Chemo on the Brain" (which is a report on an original research paper in the Journal of Biology). I have heard references before to "chemobrain" (that's the common nickname) on the CLL mailing lists that I follow as well as on the web. Chemobrain unfortunately is one of the long-term side effects of chemotherapy. As the article points out, chemobrain "may leave as many as 80% of all cancer patients with memory loss, confusion, and an inability to concentrate". Therefore, chemobrain is one of the things I'd like to avoid when receiving the various drugs given to me to fight against my leukemia. (And, I'm sure we'd all agree that I don't need anything that would lower my intellect further below where it has already slipped to by now - <g>.)

From the article:

"Scientists at the University of Rochester in New York examined the neural impact of three chemotherapeutic drugs: cisplatin, often used to treat breast, lung, and colon cancer; carmustine, used to treat brain tumors; and cytarabine, a treatment for leukemia and some lymphomas. The drugs caused widespread brain cell death in human cancer cell cultures and in live mice, even when administered at low levels, the researchers found."

The next quote from the article ~really~ brought me to attention:

"In cell cultures, the dosage needed to kill 40% to 80% of the cancer cells also killed 70% to 100% of healthy brain cells."

Wow !!! That is indeed a sobering finding - the dosage needed to kill 1/2 or 3/4 of the cancer cells also killed 3/4 to ALL of the brain cells.

Furthermore, the researchers found that:

"Particularly vulnerable were neurons in the hippocampus, an important memory center, and oligodendrocytes - cells that make a compound called myelin, which insulates neurons to allow electrical impulses to travel quickly across the brain."

~Not~ good news. Continuing:

"A particularly surprising find was the drugs' killing effect on mature, nondividing cells, which contradicts the long-held belief that chemotherapy targeted only rapidly dividing cells."

OK, so what can science/medicine do to minimize using such toxic chemotherapy drugs? In other words, what can be used to fight against a disease that doesn't do too much "collateral damage"?

What's needed are more "magic bullets" and fewer "sledgehammers"...

Many of the drugs used for chemotherapy against cancers work by interfering with DNA structure and function in cells, especially in rapidly dividing cells (which, by definition, cancer cells are, of course). One problem with this strategy is that many other cells in the body that are also dividing rapidly (e.g., hair follicle cells, bone marrow cells, cells lining the digestive tract, etc.) are generally also affected by these drugs (as evidenced, for example, by the number of chemotherapy patients who go bald during treatment).

Part of the significance of the study referred to in the above article is that it emphasized the effect of three commonly used chemotherapy drugs on cells of the central nervous system, which are ~not~ rapidly dividing cells. Therefore, the outward sign of chemotherapy-induced baldness may be more obvious, but the damage going on deep below the scalp, in the brain of a chemotherapy-treated patient, may be much more significant and long-lasting.

The concept of a "magic bullet", i.e., a drug that would target a particular disease and do no damage to the rest of the body, goes back to the late 19th Century, when some scientists found that they could selectively stain certain types of bacteria differently from other bacteria, leading to the thought that perhaps medicines could be developed that would work against just certain bacteria.

In the early 20th Century, the German scientist Paul Ehrlich was working to develop a more specific drug for the treatment of syphilis than the commonly used "sledgehammers" of the time, various toxic mercury compounds. He is most famous for developing "Compound 606", which was not only less toxic than the mercury-based drugs being employed against syphilis at the time, it was also the first drug to be chemically ~created~ (since, up to that time, medicines in common use were ~discovered~ by simply testing common substances on patients, rather than being intentionally chemically ~synthesized~ in laboratories), and was the first chemical compound ever shown to cure a specific human disease.

Compound 606 (also known as Salvarsan and as Arsphenamine) was commonly used to treat syphilis until the mid-20th Century, when it was supplanted by penicillin. Paul Ehrlich's work towards developing more specific treatments for diseases, for which he received the Nobel Prize in Physiology and Medicine in 1908, was the subject of a 1940 film biography, starring Edward G. Robinson, that was titled, appropriately enough, "Dr. Ehrlich's Magic Bullet".

I'll have more to say about chemotherapy drugs and "magic bullet" drugs for treating CLL in an upcoming entry - please stay tuned...

 

(...for now...)

Categories: Leukemia

Cycle 2 Day 22

Posted by Frederick Wasti
May 09 2012

We got home a little while ago this afternoon from Dana-Farber in Boston, having spent much of Day 22 of Cycle 2 there for another infusion of Ofatumumab. Things went pretty smoothly, I guess, although I am still pretty groggy as I type (from the Benadryl preconditioning before the Ofatumumab).

We did have a meeting with Dr. Fisher today, and we're continuing to push onwards. Dr. Fisher attributes the pulmonary embolism as mostly due to "simply" having leukemia (as opposed to the ~treatment~ of leukemia), since there is a correlation between having leukemia (and in having cancer in general) and developing blood clots that can sometimes result in a pulmonary embolism.

Well, regardless of the cause, we're dealing with it - the embolism is being treated. I will continue to inject myself subcutaneously in the abdomen with Fondaparinux for a total of six months (gee, that's about 180 "pokes" - <g>), but, so far, it's not all that big a deal (and it's not a small target, anyway - <g>).

Dr. Fisher did provide us with the results of this morning's blood tests, and it does look like things continue to improve. Here's how the total white blood cell count looks, from the time of diagnosis until today:

The first place I look on such a graph is the far right part of the curve, which does show a mostly downward trend since the start of treatment. The slope is not quite as steep as it was during the first couple weeks of treatment, but, as the bottom of the graph is now "almost in sight", any steep line might take the white cell count all the way to zero, and that would not be a good thing - <g>.

For perspective, here's the graph for my known WBC count history:

I will note a couple of things at this point (well, OK, maybe three or four - <g>):

First, my total white cell count today is the lowest it's been since perhaps early 2008.

Second, depending on whether you consider the normal WBC count range to be 5,000 to 10,000 (per microliter), or 6,000 to 9,000, or 4,000 to 11,000, my white cell count today is back to within the normal WBC count range for the first time since perhaps late 2008.

Third, despite the above two statements, I cannot be considered to be, even remotely, free of leukemia. I still have an unbalance of numbers of cells of each of the cell types, I still have proportionally too many lymphocytes, most of my too-rapidly-produced lymphocytes do not function correctly, the number of neutrophils (especially) is still too low (although gradually getting better), I still don't have a proper number of platelets, and - perhaps most importantly - the vast majority of the lymphocytes I have are almost certain to still be leukemic.

Finally, if I use my preferred "normal" WBC range of 5,000 to 10,000 (the range I employed when teaching Human Anatomy and Physiology at Bristol Community College back in the 1980s and 1990s), I now have, leukemia without also having leukocytosis (defined as too many white blood cells) for the first time in my life. (Interesting trivia, methinks.)

The good news is that the lymphocytes (both the bad and the good) do indeed continue to decline, as the graph below continues to show:

Well, if you've been reading carefully so far (and you are to be commended if you are still able to follow along with me OK - <g.), and are trying to visualize what the graph might continue to show during my treatment, you maybe are beginning to realize one of the conundrums of CLL - it is essentially ~impossible~ to actually ~cure~ a person of CLL, short of the person undergoing a very successful stem cell transplant (i.e., a bone marrow transplant).

You see, I am taking drugs that are known to kill white blood cells (one of which even targets just the lymphocytes), and yet ~none~ of these drugs can single out just ~leukemic~ lymphocytes - they are quite unfortunately equipped to kill the healthy as well as the leukemic lymphocytes, and it should therefore be obvious that it is not really plausible to kill ~every~ lymphocyte in my body in a futile attempt to destroy ~every~ last CLL cell in the process. (In fact, if we were able to magically reduce my lymphocytes to just one cell, the odds are that the survivor would likely still be a leukemic cell.)

However, despite the above somewhat gloomy picture, we ~also~ do have to realize that it is ~still~ in my best interest to reduce my CLL cells as much as possible, whether I elect to eventually submit to a stem cell transplant or not. That is to say, keeping CLL at bay is ~still~ a useful goal...

Categories: Leukemia

My CT and a PE

Posted by Frederick Wasti
May 04 2012

Midday today we went in to Dana-Farber so that I could have a CT scan (a "cat scan") of my chest, abdomen, and pelvis. This was necessary in order to see what is happening to my lymph nodes and spleen, which tend to become enlarged due to CLL, as they fill up with incredible numbers of leukemic lymphocytes. Although some lymph nodes can be palpated from the outside of the body in some places, and although an enlarged spleen can sometimes be felt just below the left ribs, it really takes a CT scan to see just what most of the lymph nodes and the spleen are really like. (In fact, my original diagnosis for CLL started out with a radiologist who, while examining an MRI of my left hip area, preliminary to eventually having my hip replaced with an artificial hip joint, found that "there are partially enlarged lymph nodes along the external iliac chain".) So, knowing what the lymph nodes and the spleen are doing is important information for judging the extent of CLL in the body.

The good news is that today's CT scan, the results of which we already found out about this afternoon (more about that below), showed that most of my lymph nodes are now quite small, and that my spleen is (in medical terms) "unremarkable". Well, that news is actually quite ~remarkable~ in that, at the time of my diagnosis with CLL (in the summer of 2010), a CT scan showed that "the spleen is enlarged, measuring 16 cm in long axis" (whereas a spleen normally is only about 11 cm long in adults), and, on another CT scan made only two and a half months ago, my spleen was judged as being "slightly larger than it was on the prior exam". So, this is all really good news, showing that my lymphocytes have not only declined in the blood (as shown by blood counts over the past few weeks of treatment), but have also declined in the lymphatic system, allowing the lymph nodes and spleen to shrink in size, and where referring to them as "unremarkable" is actually a compliment - <g>.

The bad news is that a "PE", a "pulmonary embolism" - a blockage in an artery in my lower right lung caused by a blood clot - was also found in my CT scan today. Obviously this is a serious issue, so, when this was first discovered by the radiologist this afternoon, we received a phone call at home, shortly after reaching there, asking us to return to Boston to the D-F, so that I could start immediate treatment for it. The CT scan report noted a "pulmonary embolism involving the segmental branch of right lower lobe pulmonary artery" and recommended that "immediate clinical action should be taken" for it. Uh-huh...

As it turns out, the treatment for this PE will be a daily subcutaneous injection of "Fondaparinux Sodium", which has a trade name of "Arixtra". (Most web sites say Fondaparinux is pronounced as "fon-DAP-a-rin-ux", but a few say it is pronounced as "fon-dah-PAH-rin-ux", and I find the latter easier to say - <g> - I was given two leaflets about this anticoagulant this afternoon at D-F, and one pronounces it one way and one the other.) So, I had my first injection of Fondaparinux while I was at D-F this afternoon, given to me by a nurse. However, the rest of the injections (remember that they're ~daily~ injections) will be self-administered by yours truly. I was taught today how to properly give the injections, and I will start doing so tomorrow (<gulp>). "Fun", to be sure...

Finally, I note that, while we generally pronounce "CT scan" as "cat scan", it seems to have lost its original spelling. There was a time when "CAT" stood for "computerized axial tomography", but now the term is generally shortened to "computerized tomography" and abbreviated as "CT" - but we still pronounce "CT" as "cat" for convenience, I guess. Such is progress in medical imaging... :-)

 

Categories: Leukemia

Cycle 2 Day 15

Posted by Frederick Wasti
May 02 2012

Today was Day 15 of Cycle 2 of Part A in my "Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL" clinical trial at Dana Farber, and it was a "just a regular" Ofatumumab day (with only a small dose of Methylprednisone this morning, just for pre-Ofatumumab conditioning). So, today marks the middle of Cycle 2 - i.e., two weeks ago today was Day 1 of Cycle 2, while two weeks from today will be Day 1 of Cycle 3.

There was one change in protocol today: Along with the small dose of Methylprednisone and the two tylenols, I was given Benadryl in pill form today - it was the same dosage as what an infusion would have been, but it was just a little pill to swallow (along with the two Tylenols) instead of an infusion. This was done because it has become obvious that the strongest effect I have felt during my days at D-F has been a profound grogginess due to Benadryl, and so the thought was that the effect might become less pronounced with a slower reacting pill. Well, taking a pill did slow down the amount of time it took for me to get groggy, but I still think the extent of the effect was still about the same. (However, it does take less time to swallow a pill than it does to receive an infusion of the very same med, so that, at least, is a small improvement.)

By the way, you may recall that, after the first two times I received infusions of Benadryl, the original dosage was then cut in half, so that, instead of the Benadryl turning me into a 400 pound zombie, I merely became a 300 pound zombie. (And, I may yet try out for a role as an extra on "The Walking Dead" TV series for next season - however, it won't actually be a speaking role, just a "grunting role" - <g>.)

The good news today (not overwhelmingly good news, mind you, but at least comforting news) was that the white cell count had started going down again (YAY!). After a few weeks of declining fairly dramatically, it seemed to have more or less level off for a couple weeks, so it was indeed gratifying to see this morning's blood test results start heading in the right direction again.

So, let us first look at the total leukocyte count during the trial so far:

Note that, while the rate of decline did not quite match the fairly steep slope of the first three weeks of the trial, it definitely did show more of a decline than seen over the past two weeks.

Now, to put the total leukocyte count into a longer historical perspective, let's look at the counts since the time of diagnosis:

It is, again, easy to see that the white cells are starting to go down once again. Furthermore, it should be noted that, even with the recent plateau in counts, I still have had fewer white cells in my blood recently than I have had since back before the time of diagnosis.

Finally, let's see how those pesky lymphocytes have been faring:

It can be seen that the lymphocytes have also resumed a decline (and may it continue for a while longer...).

Well, as I said above, today's blood test results were not overwhelmingly good, but they were still a pleasant sight for our eyes this morning. :-)

Categories: Leukemia