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Zero Lymphocytes ???

Posted by Frederick Wasti
Jul 30 2012

On last Friday, July 27th, my blood cell count results showed ~zero~ lymphocytes. Huh?

Now, considering that my disease is called Chronic ~Lymphocytic~ Leukemia, that might at first sound like ~great~ news, right? After all, if there literally were zero lymphocytes in my blood, then that would mean that there would have to be zero ~leukemic~ lymphocytes, too, right?

However, on the other hand, since normal lymphocytes do have proper functions to perform, and since they are supposed to normally make up something like a quarter to a third of the total white cells, then ~zero~ percent lymphocytes could not be considered good news after all, right?

Well, of course, I didn't really have zero percent lymphocytes after all - such a test result is merely the result of a sampling error in the way a differential white count is conducted.

Whenever my blood is checked at Dana-Farber, the technician counts the first 100 white cells that he/she sees in the microscope. Since my current lymphocyte count does appear to be about 1% or so (since the blood count results for several other recent days, as well as the results for today, July 30th, all indicate 1% lymphocytes), what occurred on last Friday was that - just by luck - no lymphocytes just happened to be counted amongst the first 100 cells that the technician observed. Perhaps the 101st cell he/she saw might have been a lymphocyte, or maybe the 102nd, but it is only the first 100 cells that will count.

During Part A of my clinical trial, frequent use of Ofatumumab and periodic use of HDMP were used to greatly reduce the lymphocytes in my blood, from about 50,000 per cubic deciliter at the start of Part A down to about 2,000 per cubic deciliter at the end of Part A. (Actually, the lymphocyte mortality was really much greater than those numbers would suggest, since my blood cell counts did not include the very large numbers of lymphocytes that were destroyed while my spleen and lymph nodes were shrinking down - blood cell counts really only show the "tip of the iceberg" and do not show the number of lymphocytes in the lymphatic system nor the number of lymphocytes in the bone marrow.) Ofatumumab and HDMP do most of their lymphocyte destruction in the blood and in the lymphatic system.

Now, during Part B of my clinical trial, frequent use of Alemtuzumab and occasional use of Ofatumumab are being used to attack lymphocytes especially in the bone marrow (which, of course, will also affect the number of lymphocytes in the blood, since lymphocytes move freely between the blood, the lymph nodes and spleen, and the marrow). Alemtuzumab is known for doing a good job at destroying lymphocytes in the bone marrow. And, so far in Part B, my lymphocyte counts have dropped (almost immediately), from approximately 2,000 per cubic deciliter at the end of Part A to typically only about 50 or so per cubic deciliter now (last Friday's "zero" result notwithstanding).

During the time of the trial, other blood cells, which had previously been reduced in numbers due to being crowded out by rampant lymphocyte production in the bone marrow, have been able to bounce back. In particular, my neutrophils, dangerously low at the start of the trial (which in fact was a main reason to start treatment), have risen from less than 1,000 per cubic microliter to currently about 5,000 per cubic microliter, which is a normal number for neutrophils. Note that Ofatumumab, Methylprednisolone, and Alemtuzumab did not directly foster the production of neutrophils - it was their action of destroying large numbers of lymphocytes that made space in my bone marrow so that neutrophils could be produced in normal numbers once again.

So, by looking at the total white cell count for the clinical trial up through today...

...it can be seen that the number of all leukocytes combined has gratifyingly declined from almost 60,000 per cubic deciliter (primarily due to having far too many lymphocytes) to about 5,000 per cubic deciliter (which is actually a "low normal" number).

As for the relative proportions of lymphocytes and neutrophils in my blood, by looking at their percentages during the trial up through today...

...it can be seen that the decimation of lymphocytes - the red curve - has allowed for a reversal of their relative proportions (which is actually an intentional "over-reversal", since, while my neutrophils - the blue curve - have been restored to approximately normal numbers, my lymphocytes have been reduced to ~far~ fewer than normal numbers).

However, just how many of my remaining lymphocytes are ~leukemic~ lymphocytes cannot be determined from any of the above. Obviously, most of the lymphocytes that have been destroyed had to have been leukemic lymphocytes, but - just how many of the ones that are left are actually leukemic? I am still awaiting the results of the genetic testing of bone marrow samples taken at the end of Part A, and those results might provide some indirect evidence that may help to answer that question...

Finally, some additional good news for today's blog entry is that the hives that I reported on in my last entry have not re-occurred - apparently my nightly doses of Benadryl, Zyrtec, and Tylenol do seem, at least so far, to be keeping any allergic reaction to Alemtuzumab under control. (<smile>)

Categories: Leukemia

Yikes !!! Hives !!!

Posted by Frederick Wasti
Jul 23 2012

[First, I would like to apologize for the "slowing down" of my blog posts lately - this three-days-a-week schedule for chemotherapy seems to have put a crimp in my blog updating - Sorry.]

Well, I'm well into Part B of my clinical trial now. Today is the beginning of the Week 3 of Cycle 1 of Part B, which has six 30-day cycles altogether. And, in Part B, things had been going pretty smoothly (all things considered), up until last Wednesday, so let me back up to that morning of the 18th:

I had been doing pretty well with the Part B protocol so far (i.e., no serious side-effects), but, while heading into Boston to Dana-Farber that Wednesday morning, while driving along Melnea Cass Boulevard, I started getting itchy all over (but, since it was a very general itchiness, I did try to avoid scratching too much since it was clear that it was not localized). Then, by the time we got to Ruggles Street, I noticed that I was starting to get hives - at least that's what we thought I had (I myself had never had, or had ever even seen, hives before).

When we got to D-F, I was examined, and (yes) I indeed did have hives. This was not unexpected (by other than me - <grin>), since it is not an uncommon reaction to the new Alemtuzumab that I have been receiving in Part B.

The most notable thing about getting hives, to me, was that it had happened almost 48 hours since I had received my last Alemtuzumab (back on the previous Monday morning, on the 16th). Of course, I am given injections of Alemtuzumab three days each week to keep a more or less constant level of the drug in my system, and I guess my system was finally just saying "Whoa!" - <grin>.

So, I was given extra Benadryl (back up to 50 mg, instead of my usual "merciful" 25 mg), and 1,000 mg of Tylenol, before finally being given my regular dose of Alemtuzumab (an injection of 30 mg in 1 ml of isotonic solution) on Wednesday.

Then I was told to add three items to my "night meds": In addition to the anti-viral Acyclovir that I take twice a day, including once before bed, I now have to take 50 mg of Benadryl, 500 mg of Tylenol, and 20 mg of Zyrtec, all to try to keep my immune system from having an allergic reaction (such as hives) to the Alemtuzumab.

The good news is that the hives did go away quickly (that day), and I have not had any since, and, since today is Day 1 of Week 3 of Cycle 1, that means that I've had Alemtuzumab three times without any problems since first getting the hives last Wednesday. I have also been able to go back to taking "only" 25 mg of Benadryl before receiving each Alemtuzumab injection.

And, I certainly don't have to worry about the 50 mg of Benadryl putting me to sleep at ~night~ - <smile>.

So, Part B will continue...

Categories: Leukemia

Leukos Has Been Sighted !!!

Posted by Frederick Wasti
Jul 14 2012

Yes, Leukos has been sighted again !!!

As you know, Leukos, a female humpback whale first named by yours truly in the early 1980s, is the inspiration for the name of this blog (please see the About "Leukos" page for a brief biography of Leukos and my connection to her).

Leukos likely visits the Gulf of Maine (the expanse of water between Cape Cod and the west end of Nova Scotia) every year for the spring, summer, and fall seasons (spending the winters in the Caribbean), but she has not been sighted in Massachusetts every year. She was spotted offshore here as recently as 2011, but has not been seen here as of yet during 2012.

However, on July 10th, Leukos was sighted (and photographed) by a whale watch boat operating out of Westport, Brier Island, off the west coast of Nova Scotia. Here is a photograph of her tail flukes taken during that encounter:

Compare this with my own photograph that I used on the About "Leukos" page, or with this photo of mine from 2008, below:

It is not unusual for some humpback whales in the Gulf of Maine to travel around a lot, spending the warmer months at various places off of Massachusetts, New Hampshire, Maine, New Brunswick, and Nova Scotia, while it is also not unusual for others of "our" humpback whales to be "faithful" to only certain locations (for example, the humpback named Salt has been seen on Stellwagen Bank, east of Massachusetts Bay, every year since 1976). Apparently Leukos is one of the more well-traveled Gulf of Maine humpbacks.

Please see the map below to see where Stellwagen bank and Brier Island are, relative to each other, about 250 miles apart:

Of course, 250 miles is "small potatoes" to a Gulf of Maine humpback whale, which migrates to and from the Caribbean Sea each and every year.

So, it seems unlikely that I will have another chance to see Leukos this year. However, I do believe that there will be other years for Leukos and for me, and that I may yet see her once again when she next visits Massachusetts waters...

[Thanks to Jooke Robbins of the Center for Coastal Studies in Provincetown, for alerting me to the above sighting, and to Brier Island Whale and Seabird Cruises, for making the 2012 signting photo above available online.]

Categories: General, Leukemia

Dumbfounded and/or Gobsmacked !!!

Posted by Frederick Wasti
Jul 11 2012

Wow !!!

Today was the second day of Part B in my clinical trial at Dana-Farber, and, when I got the results back from this morning's blood tests (which reflect changes occurring following Monday's first Part B treatment), I was dumbfounded (or maybe I was gobsmacked - dunno which - <grin>).

To recap, on Monday I was given a full dose of Ofatumumab, the monoclonal antibody that I had received once each week during the 16 weeks of Part A and that I will receive once each month during Part B, ~and~ I was also given a full dose of Alemtuzumab, the new (to me) monoclonal antibody that I will receive on three days each week for each of the 24 weeks of Part B.

Well, to say that the effects on my blood counts from being given Alemtuzumab are astounding is almost an understatement.

The first number I looked at today, the total white cell count, was (compared to what I was to look at next) not overly surprising - it had dropped a bit to 3.8:

My eyes then jumped down to the neutrophil percentage, and I was astonished to see that the neutrophils had climbed to ~90%~ of my white cells:

My first reaction to this was that either I had made a mistake (looking at the wrong place on the printout, say), or that the results were simply wrong (after all, how could ~9/10~ of my leukocytes now be neutrophils, considering that they were less than 1% before treatment started?).

Then I had to look at the percentage of lymphocytes:

I was amazed to see that the lymphocytes now represented only ~1%~ of my total white cells, rather than the over-90% that they represented before the clinical trial began.

My first emotion (besides surprise) upon noting the above data was a bit of joy (since, after all, my leukemia involves lymphocytes, and Alemtuzumab is ~supposed~ to reduce the number of lymphocytes), but it then turned to some disbelief, when I again recognized just how drastic a change these numbers represented (Could this all be real? - Could this all be good?).

Looking at the absolute numbers of neutrophils...

...and the absolute numbers of lymphocytes,...

...it is clear that the dramatic change in percentages was due to the incredible drop in lymphocytes alone. Of course, destroying lymphocytes (unfortunately, both the leukemic ones and the normal ones) ~is~ supposed to happen during my treatment. But, was such a huge change for real?

I did not have contact with my doctor today (as I did last Friday), or with my nurse practitioner today (as I did on Monday), so I asked my infusion nurse about my blood test results, and she said that this was ~indeed~ what was supposed to happen. Still, I remain absolutely amazed.

For my final graph today, here is how the percentages of neutrophils (blue curve) and lymphocytes (red curve) each have varied during the clinical trial:

Now, is that an ~unusual~ graph, or what? (<smile>)

I am sure I will have more to learn about this, and to say about this, soon...

Wow !!! - Just Wow !!!

Categories: Leukemia

(sort of) Just Another Ofatumumab Day (?)

Posted by Frederick Wasti
Jul 09 2012

Today was the first day of Part B of my clinical trial at Dana-Farber. It was scheduled to be a long day, where I was to be given (in the following order) 50 mg of Benadryl, two 500 mg Tylenol tablets, 30 mg of Alemtuzumab, 50 mg of Methylprednisolone, and 1,000 mg of Ofatumumab.

The Benadryl, Tylenol, and Methylprednisolone are given in Part B simply as "pre-conditioners", for helping to make the actual anti-leukemia drugs, Alemtuzumab and Ofatumumab, easier to tolerate, and the dosages and methods of administration for Tylenol, Methylprednisolone, and Ofatumumab are all the same as in Part A. However:

The 50 mg of Benadryl was given to me today by infusion, rather than in pill form, and it was the full dose of 50 mg, too. This seemed to be a case of "deja vu all over again", since 50 mg of Benadryl by infusion is what I first received back at the beginning of Part A just before being given Ofatumumab. However, after finding that I became a total zombie from that dosage and administration method, the dosage was cut to 25 mg after a couple of weeks, and then a switch was made to oral administration instead of infusion after a few more weeks, in order to allow me to be perhaps somewhat more responsive to reality. However, at least for today (and possibly for next Wednesday, as well) it was recommended that I go back to the 50 mg by infusion protocol, since I was starting a new drug, Alemtuzumab, and it was not known (yet) how I would tolerate it. And, not only were the dosage and method of administration "deja vu", the effects were, too - I was, once again, more like a "Walking Dead" actor for a few hours than I had been for most of Part A.

Alemtuzumab ("al-em-TOO-zoo-mab") (a.k.a. "Campath") is a brand spankin' new drug for me. It is another monoclonal antibody (making it, technically, not an actual chemotherapy drug at all, which is nice). Ii is similar in action to Ofatumumab, in that it targets specific molecules on the surface of lymphocyte cells, but it is also different, in that the molecule that it attacks is found on both B-lymphocytes and T-lymphocytes, so that it kills a larger variety of lymphocytes than does Ofatumumab, which kills only B-lymphocytes (and, in CLL, it is only the B-lymphocytes that are leukemic). Also significantly, while Ofatumumab is better at attacking CLL cells in the blood, Alemtuzumab is better at attacking CLL cells in the bone marrow.

Unfortunately, Alemtuzumab is notorious for not being quite as tolerable as are some of the other monoclonal antibodies (e.g., Dr. Yamin, my hematologist/oncologist at Jordan Hospital in Plymouth, refers to it as "nasty stuff"). In fact, it used to be administered only by infusion into a vein, but is now usually given by injection under the skin, since it seems to cause fewer and less "dramatic" side effects in that way.

Well, the good news I have for today is that I have not seen any noticeable reaction to Alemtuzumab that I can distinguish as being different from, or in addition to, any that I could attribute to Benadryl and/or Ofatumumab. So, today seems (sort of) like "just another Ofatumumab day", and that is good news ~indeed~! (<smile>)

[Edit, July 10th AM - it is clear that I had a bit of a "heavy head" last evening that was probably a bit stronger than I had experienced the last few times I had Ofatumumab, and I also had a bit of trouble going to sleep (which is unusual for me), and I am assuming that these may be due to the new Alemtuzumab.]

[I still have to discuss last Friday's radiologic, blood, and marrow tests, and our chat with Dr. Fisher, but I wanted to get the above description of today's treatment online first.]

Categories: Leukemia

A CLL List Reply

Posted by Frederick Wasti
Jul 07 2012

I peruse, and occasionally participate in, a couple of CLL lists. (There are also several online CLL forums out there, too, but I have found them to be less useful.) I responded this morning. directly by email, to a person who described his situation and then asked the question, "Anybody on the list have any experience with Alemtuzumab or Rituximab in combo with high-dose Methylprednisolone?", and, while I was trying to compose a concise (well, at least for me - <grin>) response, I realized that my email reply might be useful as a blog entry, too, since it did summarize my current status, between Parts A and B of my clinical trial. So, here it is. (I did make a few changes, in that I have expanded a number of abbreviations - used so much in the CLL lists - to make it easier to read here.)

Hi, [name of person].

I've been in a clinical trial at Dana-Farber in Boston, involving high-dose Methylprednisolone, Ofatumumab, and Alemtuzumab ( http://www.clinicaltrials.gov/ct2/show/NCT01465334 ). Just this week I finished the four cycles of Part A, involving high-dose Methylprednisolone and Ofatumumab, and next week I start the six cycles of Part B, involving Alemtuzumab and Ofatumumab. (There is also a long "maintenance" Part C, which can optionally be replaced with a stem cell transplant instead.)

As you said, Ofatumumab is "a monoclonal antibody supposedly more effective than Rituximab". They both attach themselves to the CD20 molecule on B-cells, but supposedly Ofatumumab latches onto it closer to the cell membrane, perhaps making it more effective. Being fully humanized, Ofatumumab may be more tolerable for some than Rituximab, as well.

I found that Ofatumumab (each week) was quite tolerable, while the high-dose Methylprednisolone (every four weeks) caused more profound, more long-term effects (not permanent, but slow to fade away each time).

My total WBC has gone from 58K to 6K, my lymphocytes dropped from 85% of total WBC to 33%, and my neutrophils went from 0.5% (my reason to start treating) to 58%. My palpable lymph nodes shrank away to nothing on the very first day, and CT scans have shown that my spleen and internal nodes have shrunk to "unremarkable" (<grin>) size.

I assume that both Ofatumumab and high-dose Methylprednisolone can take credit for the above, although I do not know which was more effective. (Of course, acting synergistically, they both probably worked together to do this.)

Part B should really start clearing out my marrow (although Alemtuzumab will hurt my T-cells as well as the B-cells, unfortunately). My first bone marrow biopsy (from before Part A started) showed 30% marrow involvement - however, my second bone marrow biopsy was performed only just yesterday, and I don't have any results from that test yet.

The combinations in this trial may be a bit "odd" (of course, that's why it's a clinical trial - <grin>) - I think the literature shows high-dose Methylprednisolone used more often with Alemtuzumab than with Ofatumumab, for example. The trial is aimed at 17p-deleted people.

I did have one serious "unexpected event" during the trial - my second CT scan (at 2 cycles into Part A) showed a pulmonary embolism not present in the first CT (before Part A). Because of this, I have been giving myself daily injections of Fondaparinux. Whether the clot was related to CLL, or to the CLL treatment, or is unrelated to either, I really don't know.

I can try to answer any questions you might have - please feel free to ask.

Carry on then...

Fred (Frederick Wasti)

dx 2010 - 17p deleted - IgVH unmutated

[I will have more to say about Friday's blood test results, CT scan, bone marrow biopsy, and meeting with Dr. Fisher in an upcoming post.]

Categories: Leukemia

The (almost) Last Day of Part A

Posted by Frederick Wasti
Jul 04 2012

Yesterday, Tuesday, July 3rd, was my last infusion day of Part A of my clinical trial at Dana-Farber. (It was scheduled for Tuesday this week since today, Wednesday, is Independence Day.) It was a pretty "routine" day, except that it took a little longer to get blood test results back (probably due to a pre-holiday "skeleton crew" manning the Laboratory Services Department), so that the actual administration of pre-meds and Ofatumumab began a little later than usual.

Part A (involving high-dose Methylprednisolone and Ofatumumab) has occupied many days of our last 4 "months" (they're actually 28-day cycles). Part B (involving additional Ofatumumab as well as a new monoclonal antibody, Alemtuzumab) will commence next week, and will last for almost half a year (six 28-day cycles). Then will come a Part C, which is a less intensive, "maintenance" series of treatments, lasting about two years (twenty-six 28-day cycles), involving less frequent doses of Ofatumumab and Alemtuzumab, although it could be optionally replaced with a stem cell transplant. (Please see http://www.clinicaltrials.gov/ct2/show/NCT01465334 if you wish to view or review the "official" description of my clinical trial.)

For Part A, we've been in and out of D-F in Boston for one to three days per week, sometimes in heavy traffic, but, fortunately, sometimes in lighter traffic, too. The HOV Lane (which we are often able to utilize, especially in the mornings) on the Southeast "Expressway" has been helpful. (Sometimes I think Diane takes me along to D-F just so she can take advantage of using the HOV lane - <g>.)

The valet parking arrangement at D-F has been great - on most days we are able to drop the car off below D-F's Yawkey Building, and then ride up and down the elevators from appointment to appointment, all the while not having to leave the Yawkey building. (The only exception is when we have to go over one of the connecting corridors, located above or below Jimmy Fund Way, to D-F's Dana Building for the occasional CT scan, such as we will do this Friday.)

Well, the blood test results for today were mostly unsurprising - i.e., most of the numbers were about the same as those from last week. Probably the nicest new number to see was the total white cell count...

...which, having dropped to 5,400 per microliter, is the lowest yet during this clinical trial. Actually, now that I think of it, when looking at the total white counts from as far back as I have records,...

...5,400 (although still within the "normal" range) is the lowest white cell count I have had since at least back to 2003. Interestingly, though, and despite the fact that the total number of white blood cells dropped this week, the percentages for lymphocytes (33%) and neutrophils (58%) both stayed about the same as last week's results, because, while they both did drop a bit during the six days between blood tests, they did so proportionally.

Actually, although I am saying that Part A ended yesterday, with Part B beginning next week, I suppose, technically, this ~Friday~ might be considered the last day of Part A. I will not be receiving any treatments on Friday, but there will be some testing (a CT scan and a bone marrow biopsy) going on, mostly to provide additional (to the blood tests) important information for judging the overall success of Part A (although it will also serve as a starting reference point for Part B).

"Are we having fun yet?"...

Categories: Leukemia