My blood takes me to school

Life goes dormant for a season.  It is not death.

So okay the shock waves have passed through me and the panics and terrors have subsided like flappy cubes of jello in a cold dish.

There are many things about the first two posts that I should change in the interest of making the right impression on strangers.  But I won't.  I just want to leave a trail of awakening here.

So when you get the slow motion death sentence, you hear things.  You mis-hear things.

For two and a half years I have delayed doing serious research on CLL.  I created a cartoon version, broad strokes, big eyes, goofy saber-toothed tiger face, sketchy.  The first two posts present the animated movie of my brain covering a vast terrain on flappy jello legs, falling into tide pools, seeing sabre toothed tigers in my reflection.

My recent visit to Mayo Clinic held a blow torch to the cartoon.  Now I need to start building a more sophisticated internal model of both the basic physiology, the disease itself, the logistics of treatment.  Etc.

If you have CLL, and are in the early stages, and have read this far, here is a paper trail of my discoveries so far.  I am building a decision model for assessing the suitability of various treatments to my specific pathology.

It starts with the initial diagnosis.  I received, and continue to receive, high quality treatment from Mayo's Hematology department, under the coordination of Dr. Sameer Parikh.  I started my journey there under the care of Dr. Letendre, who retired shortly after our first two visits.

The first tests taken on my blood in 2012 showed that my White Blood Count (WBC) was already elevated to 3000, which indicated a likely pathology but it wasn't noticed in the context of my surgery, and the prep for that.

This story is told in detail in my first post.

The research I have done over the last week has left me with some difficult realizations.

1. My status as a new, untreated patient limits the kind of treatments I am eligible for.
2. My age and pathology further limits me.
3. And finally my insurance limits me.

While there are promising new drugs called biologics, or targeted treatments, which are fine tuned to my own genetic profile, I am not eligible for them in a standard treatment format.  I might be able to get signed into a clinical trial.  The downside of that is that I might be one of the subjects in the trial who is given a placebo or an older form of chemotherapy instead of the new treatments.  It is a form of lottery, or roulette.

To further complicate matters, public forums for CLL patients are already questioning the value and safety of some of the new drugs which the FDA hasn't even approved for initial treatment.  I receive a mail digest of correspondence among one group of CLL patients, and several of them jumped on the bandwagon when the subject of idelalisib (marketed as Zydelig) came up.  One patient detailed their acute liver failure while on a course of the drug.  Another said their reaction had been so severe that their oncologist swore he would not recommend it for anyone else.  These are anecdotal reactions.

But they are what I, a newcomer to the whole scene, encounter as I try to walk down a path of education about my disease.  And they are not coming from the wild fringe of extremists who carry a grudge against all organized modern medicine.  These anecdotes come from civil, educated, cooperative patients who are willing to undergo great discomfort in the interest of wresting a few more years of life out of their situation.

I talked to Dr. Parikh yesterday, and he said my best chance was probably a combo approach with two Intravenously-administered drugs: BR, as it is referred to, is an updated regimen designed to replace the older FCR regimen which has solid research credentials, especially for people in my demographic of male near 70.

The side effects of all the drugs discussed include severe to fatal lung infections, over-all body sores, loss of taste for food, nausea, weakness, increased white blood count before it declines, a susceptibility to infection from any source which makes even going out in public a high risk endeavor at some point in treatment.

All cancer patients who have undergone chemo and radiation are familiar with these struggles.  It is only recently that the class of treatments called biologics have come through research and are in the FDA pipeline for approval.  They have caused excitement and raised hopes because they can often be taken orally instead of intravenously, they don't seem to have the same side-effects, or at least the severity is muted, or at least they are fewer for any given drug...so it seems.

I say so it seems, because there is an underlying reality to treatment of cancer in general, and CLL in specific, that makes research into the efficacy of particular regimens extremely difficult.  

On the dormant blog called CLL Topics, the author investigates several clinical trials in some detail.  While admitting that her background in scientific research doesn't make her in expert in medical trial design, she notes that the ptotocols and criteria for success in medical trials are laden with anecdotal and heuristic (unprovable but workable) shortcuts.  As a result, it is often impossible to work backward from trial outcome to determine the full set of variables being tested, and how reliable the tests are on that set of variables, and how predictive, exactly, the outcomes of the trials are.

This is because they all represent, in effect, experimentation on live human subjects.  This is a fraught subject with a history littered with atrocity and abuse.  Modern researchers/experimenters take pains to conserve priorities of patient comfort and the integrity of the methods in the face of overwhelming challenges to full scientific treatments that would yield much more robust results for future pharmacological invention.

The Nazis didn't labor under such constraints.  Curiously and controversially, the AMA and the NIH didn't either when they sanctioned experiments on prisoners, black people, poor people, soldiers and other unwitting civilians through the last century as they worked alone or with the CIA in researching syphilis treatments, truth serums, etc.

In theory and policy we have left much of that behind in the last century.  In practice it doesn't take much hair-splitting to question the whole realm of live human experiments.

For example, my doctor said I wouldn't be eligible for a first round treatment with Imbruvica, despite its approval recently by the FDA.  It is a biologic that is supposed to have far fewer and far less distressing side effects than old style chemotherapies such as chlorambucil.  It was fully approved for first round treatment in 2014.  I am not eligible according to my insurance company, according to my doctor.  He offered instead my participation in a trial, an experiment, that assigns patients at random to one of three groups: one receives old style chemo, and two receive Imbruvica in some combination.  He said my chances were two out of three of getting the advantage of the new drug.

Why can't I just get the new drug?  It is a rhetorical question.  A detailed answer would absorb too much of your time and too much of my good feelings about life.

Why can't I just get the best drug available at the moment?  And, equally important, why can't I know if it is really the best drug, or if certain aspects of the trial outcomes have been emphasized at the expense of the over-all results? For example, a recent German trial reported that the side effects of a biologic treatment were much less than with a conventional chemo treatment.  On closer examination of the published results, it was shown that only one side effect was diminished.  Other side effects were similar are greater, and much greater as the subject's age increased.

This latter question arises thanks to our source at the CLL Topics blog, who had the experience and connections to understand which pharmaceutical companies were sponsoring which trials outright, which were paying honoraria to the doctors involved in the design, etc.  Without condemning it as a corrupt system, she acknowledged that perfectly honorable people were participating in a system that could tip into misrepresentation at some stage of the pipeline, without it being clear in the outcomes.

Even representing the trials and their outcomes is a challenge when you are dealing with experiments on live human subjects.  Some trials were performed, and results reported, on fewer than 20 subjects.  According to sampling theory, which is a mathematical discipline, the minimum number of cases you need to try in a trial is determined by the total population of interest.  In this case, say, it would be something like "all males over 60 with less than 5 years remission after a first round treatment with FCR."  That might be considered the target population from which the 19 subjects were drawn.  In practice, the actual distribution of subject attributes never approaches that degree of purity.  But sampling theory tells us that if there are 20,000 males in the world over the age of 60 with fewer than 5 years remission after a first round treatment with FCR, then for a 95% confidence level and a confidence interval of 4,  our sample needs to be at least 583 subjects.  Read bout confidence level and intervals here.

Bottom line?  You can't set up a spread sheet and compare treatments across the board.

What does that mean for me?

I must consider the quality of my life now.  How many years do I have left?  What is the nature of the untreated progression of the disease?  How much will I suffer from treatment related effects, compared to the effects of the disease itself?  Who can I talk to about an objective assessment of these things?

I have to throw in the towel for the time being.  It is robbing me of sleep, any peace of mind, and severely affecting my daily routines and relationship with my wife.  And I haven't even started treatment.