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Poppin' Pills

Posted by Frederick Wasti
Mar 31 2012

The main drugs that I am or will be receiving in my Dana-Farber clinical trial protocol are Ofatumumab, Methylprednisone, and Alemtuzumab. The first two are administered intravenously, while the third will be administered subcutaneously.

However, while less "glamorous" (<g>) than the above medications, there are a few other medicines that I also have to take daily, by mouth, as pills. These are to help deal with two related factors:

First, as a person with leukemia, my immune system has already become compromised, so that I may be significantly more susceptible to infections (bacterial, viral, and/or fungal) than are most persons.

Then, as a patient being treated for leukemia, my immune system needs to be further damaged in certain specific ways in order to eventually start to improve it. (In other words, this ~is~ a case of "things getting worse before they get better".)

Therefore, I do have to take three prescriptions daily, as follows:

1. Sulfamethoxazole/Trimethoprim, a.k.a. Cotrimoxazole (generic) (brand name Bactrim) -

Cotrimoxazole is a combination of two antibiotics (Sulfamethoxazole and Trimethoprim) used for the prevention or treatment of a variety of bacterial infections of the respiratory system, the middle ear, the urinary tract, and the intestines.

In particular, Cotrimoxazole is effective on Pneumocystis pneumonia, which is a form of pneumonia caused by the yeast-like fungus Pneumocystis jirovecii. Pneumocystis is actually commonly found in the lungs of healthy people, but their normally functioning immune systems keep it in check. However, Pneumocystis can bring about an opportunistic lung infection in a person with a compromised immune system.

In a perfect example of synergy, the combination of Sulfamethoxazole and Trimethoprim is more effective than either of the components are individually. What the two antibiotics do, in a "1-2 punch" action, is to separately interfere with two consecutive steps in one biosynthetic pathway in certain bacteria and fungi - this ultimately prevents certain essential proteins in these "bugs" from being manufactured.

2. Voriconazole (generic) (brand name Vfend) -

Voriconazole is an antifungal medication that is used for the prevention or treatment of certain serious, invasive fungal infections, sometimes seen in persons who are immunocompromised. Examples of these infections include candidiasis (a fungal infection of the skin, mucous membranes, or digestive tract), and invasive aspergillosis (a deadly fungal infection that begins in the lungs and then spreads through the bloodstream to other organs of the body).

Voriconazole is in a member of a class of antifungal medications called triazoles. It works by interfering with one critical step in a biosynthetic pathway necessary for fungal cell wall production - technically, it does not so much kill fungal cells as it prevents them from reproducing (which requires new cell walls).

3. Acyclovir (generic) (brand name Zovirax) -

Acyclovir is a very commonly used antiviral drug, employed primarily for the prevention or treatment of such viral infections as those caused by the herpes simplex virus (cold sores, fever blisters, genital herpes, etc.), the varicella zoster virus (chickenpox), and the herpes zoster virus (shingles).

Viral infections can arise from picking up new, recent viruses, but they may also come from viruses that entered the body many years previous, and which still remain in the body, kept in an inactive state for many years by a healthy immune system, but which can become reactivated in a person with a compromised immune system.

From my clinical trial consent form - "Risks Associated with Ofatumumab: [...] Rare: Less than a 1% chance that this will happen [...] Progressive Multifocal Leukoencephalopathy (PML): A rare and severe viral infection of the brain. PML can cause brain damage, memory loss, trouble thinking, muscle weakness, blindness and death."

NOPE! - DON'T want ~that~ virus... (<g>)

Again, from the same consent form - "Risks Associated with Alemtuzumab: [...] Frequent: Between a 10-50% chance that this will happen [...] CMV (Cytomegalovirus) reactivation without infection. Detected on routine monitoring and treated. This is a virus that may be carried in an inactive state for life by certain individuals. It can be a cause of severe pneumonia in people with a suppressed immune system, such as those with lymphoma or leukemia."

NOPE! - do NOT want ~that~ one either... (<g>)

[As an aside, please note two ~VERY~ important points made in the above quote about CMV - First, I will be monitored routinely for CMV reactivation (and the odds are pretty good that I do not have the CMV virus in my body anyway), and, second, it would be treated if it did occur. So, not to worry...]

Acyclovir doesn't actually "kill" viruses (which are not really alive), but it does help to slow or stop the spread of virus particles. Acyclovir is not actually an antibiotic - antibiotics work only on living pathogens, and viruses are "merely" nonliving chemical "beings" of sorts.

Technically, Acyclovir can be referred to as a "prodrug", since it is in a relatively inactive form as it is administered, but it then is modified into a more active form within a patient's body.

Finally, interestingly enough (well, at least ~I~ think so - <g>), Acyclovir was originally extracted from a particular Caribbean sponge!

Well, the bottom line is that taking a handful of pills each day may be a bit of a nuisance, but it is a ~lot~ nicer than developing any of the above infections due to having a compromised immune system from leukemia and from leukemia treatment.

Categories: Leukemia

Allopurinol and TLS

Posted by Frederick Wasti
Mar 30 2012

This morning I took my last Allopurinol pill. I was prescribed Allopurinol for the first ten days of the clinical trial. Allopurinol is often prescribed for people with gout, which generally involves a buildup of uric acid crystals in the joints. However, in my case, Allopurinol was prescribed as a preventative medication against Tumor Lysis Syndrome (TLS).

"Tumor lysis syndrome (TLS) refers to the constellation of metabolic disturbances that may be seen after initiation of cancer treatment. [...] A potentially lethal complication of anticancer treatment, tumor lysis syndrome occurs when large numbers of neoplastic cells are killed rapidly, leading to release of intracellular ions and metabolic byproducts into the systemic circulation. Clinically, the syndrome is characterized by rapid development of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute renal failure."

"Acute renal failure" - Ouch !!!

Basically, the number of blood cells killed during the onset of treatment may release a large amount of several toxic breakdown chemicals, especially uric acid, into the bloodstream, which presents quite a burden for the kidneys to handle.

Technically, Allopurinol is "a xanthine oxidase inhibitor, which inhibits uric acid production". (Right - <g>.) Basically, the Allopurinol minimizes any buildup of uric acid, in this case not for preventing gout, but for minimizing damage to the kidneys.

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?)

(And, of course, I have been instructed to drink lots of fluids all day at home, a requirement that Diane helps to enforce.)

So, having taken my last Allopurinol pill means that I've passed a milestone of sorts, I guess, because, when it comes to Tumor Lysis Syndrome, it's not worth kidney-ing around. :-)

Categories: Leukemia

About "Leukos"

Posted by Frederick Wasti
Mar 29 2012

Well, I figured it was about time for me to explain why this blog is called "Leukos". (Weren't you wondering?) So, I just finished the "About Leukos" page with the background for the name. Just FYI... :-)

Categories: General, Leukemia

Just Sittin' in the Chair

Posted by Frederick Wasti
Mar 28 2012

Yes, as I write this I am sitting in an infusion chair (it also reclines) in Room YC-808C on Floor 8 of the Yawkey Building at Dana-Farber Cancer Institute in Boston.

Earlier today I had a round of intravenous Benadryl (also used to help the actors in "The Walking Dead" perform) and have since started a full dose (100% this time, not 30%) of Ofatumumab ("oh-fah-TOO-moo-mab"). The dosage started at a slow rate, and then, at intervals, the rate of infusion gets "bumped" up.

I am doing well ("as we speak"), with no obvious side effects from the Ofatumumab (at least that I can distinguish from the leftover Benadryl), so that is encouraging. I guess I have a pretty good case of a "heavy head", but it's not even a headache. I also guess I feel a bit "washed out".

The people here at D-F are ~all~ super-super people.

I saw Michele Walsh, Dr. Fisher's Nurse Practitioner, and she brought the lab results for the blood taken from me first thing this morning. The good news is that some of the numbers have started to change, ~and~ in the right direction. It seems as if progress is being made in the ongoing battle between Fred's normal cells and Fred's aberrant cells. Yay!

I do have to believe that today's infusion (the first with a 100% Ofatumumab dose) is continuing to wreak havoc on the previously cocky little band of leukemic lymphocytes within, and maybe next week's numbers will be even better... :-)

I do have another three or fours hours to sit in this chair, though, in the meantime...

Categories: Leukemia

Week Two

Posted by Frederick Wasti
Mar 27 2012

For week 2 of my treatment plan I have to go to Dana-Farber for "only" one day. However, it will be a long day.

I am supposed to start with an intravenous round of Benadryl. Last week I thought that the amount of Benadryl seemed perhaps excessive - that is to say that the strongest reaction for my body to deal with last week was the "zombie-like" effects that it caused. I discussed with Kathleen McDermott about the possibility of cutting back somewhat on the Benadryl, and she did say that it ~might~ eventually be possible to do so. However, here in the second week I am supposed to receive the full 100% dose of Ofatumumab after the Benadryl, and I will likely need all of the anti-allergenic effects of the Benadryl that I can get. So, we'll see...

Some of the "novelty" (<g>) of receiving all these infusions is now gone, and a certain amount of tedium is now part of each treatment day now. However, there is also a new tension involved (although I won't quite call it "excitement") - it does seem as if now I am indeed in a battle, and, after a sometimes frustrating year-and-a-half of Watch and Wait, I am now actually doing something active against my disease, against the CLL. And, there truly is a certain satisfaction involved in that...

Categories: Leukemia

Treatment Days 2 and 3

Posted by Frederick Wasti
Mar 23 2012

For both treatment days 2 and 3, the "main course" was an infusion (a "booster shot"?) of HDMP each day. Since I did not receive the Benadryl or the Ofatumumab on these two days, they not only went quicker, the treatments also seemed to cause fewer side effects. Nonetheless, having large amounts of Methylprednisone over a period of three days has definitely had an effect - I do feel different. There are a number of possible side effects that people may experience from HDMP, but the two that I seemed to settle on were a vague sense of "jitteriness" and a difficulty in falling asleep (which was surprising - I am usually a pretty good sleeper). I was prescribed Lorazepam (generic Ativan) to help with nausea and insomnia, and I have used the Lorazepam a couple of nights now for the insomnia. (I have been prescribed a whole bunch of other meds, too - I'll discuss these in future posts.)

Well, the first week is over. I'm off and running.

Categories: Leukemia

First Day of Treatment

Posted by Frederick Wasti
Mar 21 2012

Having been accepted into the Dana-Farber clinical trial, it was now time to actually start the trial - I am to be given treatment for three days this week.

Today I started with a round of intravenous high dose Methylprednisone (HDMP) (which will also be repeated tomorrow and the next day) - this is a steroid that has been used in many cancer treatments.

Methylprednisone - "A synthetic corticosteroid with anti-inflammatory and immunomodulating properties. Methylprednisolone binds to and activates specific nuclear receptors, resulting in altered gene expression and inhibition of proinflammatory cytokine production. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cell populations."

As I see it, the Methylprednisone will be helpful in reducing inflammation while, at the same time, facilitating the action of the Ofatumumab, the other drug I would be taking in this part of the trial, and may kill some aberrant cells in its own right.

I was then given an intravenous infusion of Benadryl, which I believe is to prevent or at least minimize allergic reactions to the Ofatumumab. While the administration of the HDMP went pretty smoothly, the effects of the Benadryl were profound. I felt like I weighed about 400 pounds and, when I moved, it seemed I was swimming in molasses.

Finally I was given the infusion of the Ofatumumab. This took several hours, and was the treatment that might have caused the most problems.

Ofatumumab - "A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development."

Ofatumumab is the first "big gun" in my treatment. Ofatumumab is a "monoclonal antibody" that will directly attack my aberrant lymphocytes. Unfortunately, it is not a perfect "silver bullet", in that it will attack certain other healthy cells, too. But, the fight is on...

I did experience some skin and scalp itchiness during the administration of the Ofatumumab, but that was about it. I was told today, however, that every trial participant receives only a 30% dose of Ofatumumab the first time - next week and thereafter the dose is upped to 100%. We'll see how that goes soon...

Categories: Leukemia

Screening Day is a Success

Posted by Frederick Wasti
Mar 14 2012

In order to be accepted as a participant in a clinical trial, one has to meet several inclusion criteria and also, at the same time, avoid matching any exclusion criteria. (To some extent, one has to prove that he/she is "sick enough" but "not too sick".)

So, I spent much of today at the Dana-Farber in Boston getting "screened", and I did OK, in the sense that I was accepted into the trial (which is scheduled to get under way for me next week).

I had a meeting with my D-F hematologist/oncologist (Dr. David Fisher) and with the nurse who will handle the nitty-gritty arrangements of the trial (Kathleen McDermott). I had "some" blood taken from me for various and sundry tests for me as well as for research (~21~ vials of blood - I couldn't believe the number of vials involved - <g>), and I had an EKG. The "high point" (yeah, riiiight) of the visit was the bone marrow biopsy (not very "pleasant", but it wasn't the End of the World, either - <g>).

For "some reason" I didn't have to have the "serum pregnancy test". ;-) And, I was lucky enuf not to have to get another CT scan (i.e., another "cat scan", as if I might be hiding any cats that they could detect on some kind of a scan or sumpin') - the CT scan that I had just a couple of weeks ago at the Jordan Hospital apparently was accepted as current enuf for starting the trial.

There was plenty of paperwork to sign - consent forms for this, consent forms for that, etc. I guess the common expression is "it was like I was signing my life away", but, for me, I was actually trying to sign my ~disease~ away - <g>. I do feel really good about the trial for what it will do to the nasty CLL cells (yes, I know that they are my own cells, after all, but that doesn't mean I still have to like 'em - <g>).

So, I will be starting my clinical trial next week. If anyone wants to see some online details of this particular trial, please see Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL .

Categories: Leukemia

A Clinical Trial Just for Me

Posted by Frederick Wasti
Mar 07 2012

Chronic Lymphocytic Leukemia (CLL) is only one type of leukemia. However, unlike some other leukemias, it almost seems to be a family of leukemias. While some people discovered to have CLL will have the disease for a very long time, and may never even need treatment for it, other people with CLL will be found to have a rapidly progressing disease with poor chances for survival.

CLL is diagnosed most often in middle-aged and elderly persons, and, for many of them, a relatively benign disease progression can often be expected. CLL can also be found less commonly in younger people, and they, unfortunately are more likely to have a more rapid progression. My age at diagnosis was probably just a bit lower than "average", and, unfortunately, my CLL was not to be of a "chronic" (as in "persistent" or "long-lasting") nature.

Medical science has come a long way (but still has a long way to go) in understanding disease such as CLL. Ten or twenty years ago, for example, doctors would find that many CLL patients could last a long time, often without treatment (or with the less sophisticated treatments that were then available), but that a few patients would respond to treatment poorly or even not at all. Great improvements in diagnostic techniques nowadays, however, show that CLL affects a person variably, depending on the presence or absence or status of several interrelated genetic and cytological factors

I will delve into some of these factors later on, but I will mention one right now, as it is very relevant in the progression of my disease and its treatment.

My CLL might sometimes be specifically be referred to as "17p-deleted CLL". What this signifies is that, while all of my non-leukemic body cells and blood cells have relatively normal genes on relatively normal chromosomes (23 pairs in number), my leukemic lymphocytes (that likely all arose from just one cancerous cell some years ago) have a deletion of the short end of chromosome number 17. (The short end of each chromosome is called the "p" end, while the long end is called "q".)

The problem with having 17p-deleted CLL is that it is very difficult to destroy the aberrant cells. (I will try to explain the reasons later.) For the vast majority of current CLL patients, a concoction of three drugs called "FCR" (for now, let's just use the initials for each of them) is considered the "gold standard" of treatment. However, for the few percentage of CLL patients that are 17p-deleted, the (so-called) "gold standard" does not work very well at all - FCR depends upon the leukemia calls having a fully functional pair of 17th chromosomes.

I have been unwilling to "try" FCR for as long as I have known about the 17p-deleted status, but I am about to start a clinical trial at the Dana-Farber Cancer Institute that is specifically tailored for us 17p-deleted people. In fact, the title for the trial is "Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL". More about this later...

Categories: Leukemia

Time for Treatment

Posted by Frederick Wasti
Mar 06 2012

I was diagnosed with having Chronic Lymphocytic Leukemia (CLL) during the summer of 2010.

I was not having any "leukemia symptoms" at the time - rather, an MRI scan of my left hip (investigating the hip joint's status for an eventual hip replacement) showed some enlarged lymph nodes that the radiologist reported on. A moderately rising white blood cell count confirmed that I likely had leukemia.

As I will explain in later entries, CLL is a bit unusual in a number of ways. One is that treatment to combat it does not usually begin immediately, unlike with most cancers. It has been known for some time now that early intervention for CLL does not prolong life. Instead, the strategy for the first "treatment" for CLL is to do nothing at all, which is known as "Watchful Waiting" or "Watch and Wait" (or maybe "Watch and Worry"). Then, later on, when symptoms become more pronounced and/or a person's health starts to be compromised, a treatment regimen will finally be begun.

My period of "Watch and Wait" went on for about a year-and-a-half. During this time the principal symptom I felt was an increasing level of exhaustion. However, within my bloodstream, my bone marrow, and my lymph nodes and spleen, a battle was slowly taking place. My aberrant lymphocytes had been gradually supplanting and overwhelming my normal lymphocytes, and my neutrophils, now crowded out by rampaging neutrophils, were in a free fall. (I will discuss blood cell types in a later post.)

My hematologist/oncologist at Jordan Hospital in Plymouth, Hannah Yamin, said it was now time to start treatment. I scheduled an appointment with my "other" hematologist/oncologist, David Fisher (who had previously offered his second opinion thoughts when I was first diagnosed), at the Dana-Farber Cancer Institute in Boston, to discuss my treatment options.

My appointment with Dr. Fisher is scheduled for today, 3/6/12.

Categories: Leukemia

Hello, World !!!

Posted by Frederick Wasti
Mar 01 2012

Hello, World !!!

Categories: General, Leukemia