One aim of treatment is to not treat aimlessly

"What is the aim of treatment?"

Dr. Terry Hamblin has just made two posts to his blog under that title that shed some light on the question. They offer some additional perspective for those of you who have read my discussion Outwitting the dragon: Playing the treatment game.

Hamblin’s posts are worth a read. Among other things he discusses how the medical establishment has approached CLL by way of the more aggressive treatments needed for acute leukemia.

“Most doctors who design clinical trials for CLL have trained as acute leukemia doctors,” Hamblin writes. “Faced with a disease that may span decades they revert to type. Pharmaceutical companies are not much interested in a clinical trial that may last 20 years -- their patents will have run out. Current clinical trials, by common consent, have abandoned overall survival as an end-point; instead they have adopted complete response rate and progression-free survival as surrogates.”

Hamblin goes on to explain the problems with this, that complete response rates and progression-free survival are in the eye of the beholder -- depending on the test used to measure them -- and do not necessarily correlate with overall survival. It’s all a rather messy business, where a certain degree of guesswork is inimical to the process.

So, what is the aim of treatment?

Hamblin leaves that question open, so I will throw in my two cents and provide the answer as I see it:

To maintain a good quality of life for the patient for as long as possible.

Notice I said “good quality of life.” There’s the rub. In a disease that is chronic, that may or may not progress very far, or that may progress rather slowly, what is the point of treatment that might reduce the quality of life?

In fact, maintaining a good quality of life for as long as possible may also involve not treating or treating less.

Treatment of CLL is seldom a necessity if one defines “need” as something that has to be done or the patient may soon die without it. CLL patients do not die of high lymphocyte counts. Most often they die of infections that their compromised immune systems are no longer able to fight off. From what I’ve read, this seems to result from two things:

One, in end-stage CLL, the mutant B cells can so completely infiltrate the marrow that other cells, such as infection-fighting neutrophils (not to mention red blood cells and platelets) can no longer be produced. Or:

Two, complications from chemotherapy, which involve collateral damage to the immune system, have left the body neutropenic, practically devoid of T cells, and unable to mount a defense against invaders.

It seems to me that number two is the cause of more problems for more patients than number one. If I had another day or two, I could list so many scary side effects from chemo that one might think that the very act of undergoing it is suicidal.

It is not, of course. Chemo has its place. It’s just that in CLL, when we are talking about overall survival and quality of life, that place may not be as front-and-center as it is with other cancers. Doctors trained to fight cancer -- not just acute leukemia -- have a hard time with the concept of watching it spread. They revert to type.

Complications from chemo can also have the unintended effect of ramping up the disease, making it resistant to many therapies, by selecting for treatment-resistant CLL clones. If you get a remission that lasts three years and have burned most of your bridges, what is the point? Unless there is a pressing medical necessity, why not wait out those three years, or as many of them as you can, and then start treatment? (Sorry, vanity is not an excuse. None of us wants to look like a chipmunk, but I’d rather be a living chipmunk than a dead Adonis.)

So when I look at the question of when to treat and with what -- which is an enormously important part of the equation -- what are the factors that it boils down to in my mind? And what have I come to regard as a “pressing medical necessity?”

Obviously there are different factors at work in different people. (People with aggressive CLL have a whole ‘nother can of worms to consider and should probably ignore much of what I’m saying.) I can only speak for myself. But here is how I look at it:

So far my body has managed to cope with CLL for what I believe has been at least ten years. The rest of my immune system is weakened but still more or less functional. Typhoid Charlene came to visit and I was the last to get her cold and the first to get over it. My neutrophils are always in the normal range, even after treatment with Rituxan. There is no point yet in throwing my immune system for such a loop that it becomes almost completely useless.

So what would make me think that it's time to risk a little loopiness? Well, any one of the following:

1. If my platelets were trending downward and dropped to a point --and stayed there -- that I would be unable to clot blood and might suffer a severe hemorrhage. Say around 40.

2. If my hemoglobin (HGB) dropped to the point that I started suffering from anemia, leaving me weak and tired and left with a diminished quality of life.

3. If my liver function were seriously compromised, or if the CLL was having some other unusual or rare effect -- paraneoplastic pemphigus on the skin, for example -- that it might lead to a debilitating or life-threatening second condition. Hamblin points out that CLL cells migrate throughout the body, even into the brain, and one never quite knows what will happen when they take up residence somewhere. The "monkey wrench" factor is part of living with the disease.

4. If the disease began to take a more aggressive course, showing a sudden ramping up of symptoms, perhaps caused by a clonal evolution, that became noticeable in rapid lymphocyte doubling time or dramatic increase in lymph node size.

As many of you know, I have already been treated three separate times with Rituxan. My doctor and I are making the calculated guess that this mild treatment will keep the disease under enough control that I can continue to live with a good quality of life. So far this has worked, normalizing (or close) the lymphocyte count in the blood, reducing many nodes, keeping the spleen in check, bumping up my platelets during treatment, and hopefully keeping errant colonies of CLL cells from getting into too much mischief elsewhere.

Were I to leave the disease uncontrolled, I believe the day would arrive sooner rather than later when mild treatments alone might not suffice. I am IgVH unmutated, and therefore the CLL reproduces faster. There is no doubt that the faster it reproduces, the more problems there will be.

But if Rituxan did not exist, I would not go in for treatment at this point.

The blunt fact is that chemotherapy is not curative, and that it inevitably, to one degree or another, has side effects that can and will diminish one’s quality of life. Even Rituxan is not risk-free, destroying as it does normal B cells as well as the mutant ones; this includes memory B cells forged from fighting previous invaders, which can play an important role in secondary immunity. It may also have a negative effect on immunoglobulins in some patients.

There is a Stage IV CLL patient who posts to an internet list on occasion. She had fludarabine, once, many years ago. She has now opted for what is called palliative care -- care designed to relieve symptoms rather than cure a disease -- and in her case, this means red blood cell transfusions. This has worked for her for two years, much to the amazement of her doctors. Her platelets are also below normal, but the numbers have bounced around and she has required no transfusions in that department. She has burned no bridges during this time and reports having a good quality of life. She is accomplishing precisely what I would define as the aim of treatment.

What is wrong with her approach? Nothing, other than that it flies in the face of conventional wisdom. But haven’t we all learned by now that CLL itself flies in the face of conventional wisdom? And that, short of a stem cell transplant, all therapy for CLL is -- guess what? -- "palliative"?

In my view, failing to recognize these facts gives birth to any number of dangerous assumptions and unnecessary, precipitous acts.

Attack of the hair loss bozo

I am always interested to read the comments people leave about my posts, and a link to the comment system can be found in light blue at the bottom of each post. Since I want to enable the most people to comment with the least amount of hassle, I have enabled the software to allow anyone to comment, not just those who have signed up with Blogger.

These comments often add an extra dimension to the post, and I am grateful that they seem to be quite positive. I don’t mind ones that take issue with a point, or a post, though. I am a civil libertarian when it comes to the free flow of ideas.

What I am not a libertarian about is spam. So far I have found a total of three “comments” left by some guy who claims his name is Mike, and who always includes a link to a website promising a hair loss “cure.” These comments are of the generic “great blog!” variety and obviously the person hasn’t bothered reading the blog, other than seeing the word “leukemia” and thinking “chemotherapy” and then thinking “hair loss.”

And then, like some ravenous Ferengi, thinking “profit.”

This little slice of internet life is as amusing as it is annoying, and what amazes me most is this: How much of a bottom feeder do you have to be to search out cancer blogs, then insert comments after posts linking to your website? If this is your method of drumming up business -- or of gaining traction in the Google search results ladder -- then I would highly recommend not quitting your day job as a “sandwich artist” at Subway, should you be so lucky as to find employment outside the prison system.

I knew something was fishy when I saw one comment that said “fun blog!” This blog may be somewhat entertaining at times but CLL is not fun, and neither is coping with it. So I deleted that and in its place Blogger inserted a note that reads: “This post has been removed by the blog administrator.”

I wish the Blogger software would allow me to explain why comments are deleted; since it doesn’t, I feel compelled to explain it here. I am not deleting comments that disagree with something I have said. I am deleting spam posts that are intended to promote someone’s website. So if you see that “removed by the blog administrator” line, it means there is one less opportunity for you to learn about some bozo’s miracle hair loss cure.

By the way, I have had a receding hairline since the age of 13 –- yes, 13, and I had a bald spot at 16 -– so I know all about the incurability of hair loss. I even once went to some guy in Manhattan, Dr. Philip Kingsley, who billed himself as “the world’s foremost trichologist.” (After all, one wouldn’t want to see the world’s second-best trichologist, would one?) Despite being sent home with several bottles of shampoo and salve with magical names promising a verdant world of hair, nothing stopped the inexorable progress of baldness except for age.

It’s now slowed to a trickle, or would that be a trichol?

Outwitting the dragon: playing the treatment game

Like most CLL patients, I do a lot of thinking about chemotherapy. What would be most effective against my brand of CLL while having the least harmful side effects? If and when my treatment of choice becomes ineffective, what’s next?

This would all be a rather fascinating puzzle if it were not for the fact that it is a life and death matter. I feel like I am playing chess with unknown forces shrouded in fog on the other side of the table. Thanks to prognostic testing, my track record with treatment, and the symptoms I have presented over time, I can see perhaps half the pieces on the board. I never know if my opponent will produce a pawn, or a bishop, or a queen out of the mist.

But I play the game. I have to. Over time I get a little better at it, a little more comfortable -- but never too comfortable -- in my moves.

It seems that for some patients there is a playbook but not for me. Those with truly indolent cases might never need to think much beyond Rituxan or chlorambucil. Those with truly aggressive cases can skip a lot of moves and go right to a disease-nuking regimen followed by a mini-allo stem cell transplant. Those in the middle, like me, have no clear choices.

For the record, I am IgVH unmutated and ZAP-70 positive, both bad indicators. But these are held somewhat in check by a couple of good factors: I am CD 38 negative and have an unknown chromosomal aberration (i.e., a “normal” FISH test result) that appears to be on the less problematic end of the scale. (If all this sounds like gibberish, get thee to CLL Topics and learn what this stuff means. You can’t play the game very well without knowing it.)

According to Dr. Terry Hamblin’s analysis of mongrel patients who are unmutated but who are also CD 38 negative, the median survival for people like me is 15 years. I have learned not to take such things as a death sentence (see my post Riding the Curve). But I do accept that I am in a group that must tread carefully in order to beat the odds.

Making this game more of an, um, “challenge” is the fact that while I was diagnosed in 2003, I am fairly certain that I have had the disease for at least 10 years. Prior to diagnosis, my last CBC had been in 1996. I recall my then-doctor telling me that my white count was a little high, and that it was probably just an infection, but that I should consider have it retested in a month. Being 39 years old, feeling fine and still blessed with illusions of immortality, I sloughed it off and went about my business. I do not recall the count, and the doctor no longer has my records, and like an idiot I didn’t ask for a copy, but I believe it was in the low teens.

That I was diagnosed seven years later at Stage 2, with swollen spleen and lymph nodes and an absolute lymphocyte count of 130,000, is entirely consistent with how one might expect the disease to progress. In 1999, I had a rather dramatic-looking squamous cell skin cancer, and such cancers are more frequent in CLL patients; I had another in 2005, and so I know I am prone to them. Though diagnosed in September 2003 and unaware of the swollen lymph nodes in my neck, once I knew what to look for I began to think back to December 2002, when I had noticed, while shaving, that I was getting a bit “jowly,” which I chalked up to the vagaries of aging. To my mind, the jury of circumstantial evidence points to my having acquired CLL, if “acquired” is the right word, in 1996 or even 1995. I was very young, some might say precocious, and my “watch and wait” came and went without my even noticing it.

That, I believe, was a blessing, because in all likelihood I would have started treatment -- made a big move on the board -- sooner than I actually did. And if I have learned one thing, it is that there is no point in premature treatment. And I would have embarked on this course in the pre-internet era, or at least when very little information was available online. (And this was also the pre-Rituxan-in-CLL-era, and that was the treatment I ultimately chose.)

As a result, I would probably have relied solely on the advice of my oncologist, who would have been the fludarabine-happy and somewhat clueless Dr. Lippencot that I have written about previously. This means that by now I might have been fludarabine-refractory, perhaps having acquired another, more worrisome chromosomal mutation making me resistant to any number of treatments. Not to mention that, since fludarabine severely depresses T-cell function, and T cells surveil against squamous cell cancers, I might have come down with a disfiguring or even fatal aggressive skin cancer. Perhaps I might have gotten it from walking hatless and sunscreen-less over the scenic half-mile path from my home to Lippencot’s office, pausing to dawdle over desert wildflowers or to watch bunnies scurry amid the bushes. In retrospect, I could well have been on my way to landing on the bad end of the mongrel median.

The number of bullets I may have dodged by being ignorant is astounding. But ignorance is no longer a benefit. Now that my CLL is flowering, as it were, knowledge is power.

Twelve thoughts on how to play the game

So what have I learned?

First, there is nothing wrong with being slow and deliberate, no matter how many people (read: doctors) are shouting at me from the sidelines to do something.

Second, the more you know about your CLL, the better. It is tempting to not want to know the results of prognostic tests. But if you want to play the game with any hope of success, if you want to see a few more of the pieces on the board, you have to suck it up and learn your IgVH status, your CD 38, your FISH results, and your ZAP-70 (keeping in mind that the latter is not yet standardized and is still a work in progress). As you learn these things, remember that they are only guides to what might happen, not guarantees. And that they do not provide the complete picture, for there are no doubt some other prognostic indicators hidden in the mist, ones we will only come to know in the future. But they can nonetheless indicate to you that some moves might be better than others. It has now been shown that fludarabine and Rituxan are of little use in patients with the 17p deletion, for example. Campath, not usually the frontline therapy for any other kind of CLL, may be the more logical choice. But if you don’t have the FISH test, and don’t know you have the 17p, your doctor will more than likely steer you toward something involving fludarabine and Rituxan. (And for breaking news on how different groups with different prognostic test results respond to RF, read a review of the latest report by Dr. John Byrd at CLL Topics; knowing your prognostic status and these results might be helpful.)

Third, there are other factors at work besides CLL that might affect treatment choices. In my case, squamous cell cancer is a big issue and tips the scale against using highly immunosuppressive drugs such as fludarabine and Campath. Not that I won’t use them one day, but there will have to be powerful reasons for my doing so, ones that override the skin cancer issue. Autoimmune diseases, such as AIHA or ITP, can also play a role in treatment choices. Being Coombs test positive, I am a candidate for AIHA. Drugs that may trigger it are therefore a concern. Almost every drug used against CLL has some potentially ugly side effects and it is writ large on Page One of Logic for the Compleat Doofus that these should be researched thoroughly before embarking on any treatment. People with heart trouble, for example, may want to think twice about the “H” in CHOP (doxorubicin) and the “M” in FCR+M (mitoxantrone). As we have learned through Chaya Venkat's reporting in the case of the latter, not every clinical trial operator is going to inform you of the full potential of a drug to screw with your system. Please do not assume that your doctor knows, or will tell you, all the possible side effects of a particular treatment. (Google is your friend; use it!) And never forget that the side effects of chemo can, for some people, be worse than the disease itself.

Fourth, learn to differentiate between what is a compelling reason for treatment and what is a not-so-important reason to treat. This is a hard one that I’m still grappling with, and it’s one that many doctors have trouble with as well. You may recall that Dr. Lippencot and her partner felt I needed treatment solely because a lymph node “might cut off” the bile duct to a kidney, which, it turns out, is not a common concern. And we should all know by now that good doctors treat the patient, not the blood count: Doctors who start treatment when the WBC crosses a certain line, such as 100,000, make Lippencot look like a candidate for the Nobel prize in medicine. And let's remember that two blood test results in a row are just that, and only with a third and fourth do we begin to sense a real trend.

Of late I have been dealing with spleen issues. Mine was swollen to 18 cm at diagnosis, reduced to normal after my first course (8 weeks) of Rituxan. It grew back over time and the second course (4 weeks) of Rituxan did little to reduce it. Facing the need for treatment the third time, I pondered adding more toxicity to my white bread Rituxan in the form of prednisone or methylprednisolone. I wondered about low-dose chlorambucil, or perhaps even low-dose fludarabine. My doctor brought up the possibility of R + CVP. And then I wondered about the consequences of just living with a large spleen. Sure, it could get ruptured in a car accident. But so could a lot of things.

I decided to look in the ACOR archives to review other patient experiences. There I found one person with an “enormous” spleen of 14 cm following a doctor’s advice to rush into treatment, while another person with a “mildly swollen” spleen of 16 cm has lived with it for years, an arrangement with which their doctor is entirely comfortable. Some doctors -- the better ones, anyway -- will rely on the NCI Working Group guidelines to determine if treatment is warranted. But even here, there is some wiggle room that requires understanding an individual patient’s case and how a patient’s quality of life is being affected. Take my big spleen (please!): If platelets are normal and there appears to be no undue internal problem being created, so what if the damned thing is more than 6 cm below the costal margin (rib cage), which the NCI defines as the point of no return? The NCI guidelines are valuable and should not be dismissed, but I do not see them as some sort of holy book. They are the consensus of a number of top doctors based on a large number of cases, which brings us to:

Fifth, keep in mind that CLL is idiosyncratic and that all cases, and results, are individual. Take blood counts. Some people function fine with an ALC of 200,000, while others have multiple problems at 50,000. Some patients report severe fatigue, while others, like me, have no sign of it. Let’s look at the NCI guidelines again: If one feels fine and is otherwise functional and is able to clot blood with platelets at 70 -- 30 below the NCI trigger and some 70 below normal -- should one treat? Well, there are some doctors who wait for platelets to drop to 50 or 40 before starting treatment, and I side with their conservative approach. (That’s just my opinion -- worth, as always, exactly what you’re paying for it.) Yes, I believe it warrants heightened watch and wait. But treatment is always the last thing to do in CLL (after all, the disease will inevitably return, and the longer you wait, the more treatments will improve). Another point: Just because a majority of patients respond to Treatment X in a certain way does not mean that you will. You could do better, you could do worse. When you move a treatment piece on the board, you are always taking a risk. You cannot know for sure how your opponent will respond. Once you do know -- and I now have a pretty good idea of the effectiveness of Rituxan in my case -- you can plan your next move accordingly.

Sixth, question the conventional wisdom. Some treatments, especially those promulgated by popular doctors, can gain a bandwagon effect among CLL patients. A lot of patients (and local doctors) have hopped on Dr. Michael Keating’s Texas-sized RFC express, for example. Dr. Hamblin, who often recommends the older and decidedly unsexy drug chlorambucil, makes a compelling case that heavy-duty treatment may not always be warranted. Chaya Venkat, the CLL Topics science writer and patient advocate, is prominent in the school of thought that Rituxan-based immunotherapy may be a good low-toxicity choice for some patients. Again, remember that your personal disease characteristics and individual health factors will play a role that might mitigate for or against a particular course of action. In CLL, one size definitely does not fit all and it can pay to think outside the box.

Seventh, think about the long-term consequences. With every reward there comes a risk. This is a biggie that I revisit over and over again in my posts. If you make a certain move, how might that affect moves you can make in the future? I have had three courses of Rituxan within the past two years and have achieved 23 months of disease control with it. While I did not know my mutational status when I chose this path -- the test was not generally available then -- the new Byrd report informs me that unmutated patients using RF as a frontline therapy can go a median of 31 months before the disease returns. So I am close to meeting and beating that median, and I have avoided the toxicity of that regimen, and not only am I not fludarabine refractory, I am still fludarabine-naive. If and when I use it, I should get a good response from it, which is a far trickier proposition for those who have already used it. (And its synergy with Rituxan should help boost the effectiveness of the monoclonal, since I am obviously not naive to that.)

Here's another example (from which you might gather what my current thinking is about what to do if Rituxan montherapy begins to fail me): It appears that most chlorambucil patients will later respond to a combination therapy such as RF or RFC. The reverse, however, is not true. So using chlorambucil (perhaps in combination with Rituxan) might buy you time. (Then again, for your particular CLL, it may be a waste of time. No one said the game was not maddening!) Another example: if a stem-cell transplant may be in your future, you will want to preserve your opportunity to get one very deep remission, which is what is needed prior to the transplant, and which is a key to success. So if you repeatedly subject yourself to heavy-duty chemotherapy, to the point that nothing works very well when transplant time comes, you have probably shot yourself in something more important than the foot. Finally, keep in mind that chemo-naive patients usually have the best response to treatment, so choose your first treatment wisely.

Eighth, assess the magnitude of your disease and the magnitude of the response. It will not hurt a Stage 0 or 1 patient with decent prognostics to experiment with EGCG (green tea extract) alone as a means of disease control. But if you are at Stage 3, unmutated with the 11q or 17p deletion, wasting time on EGCG alone is time you could be spending on a more effective treatment. I suppose a way to look at it is: Little drugs for little disease, big drugs for big disease, aggressive therapy for aggressive disease. As much as I believe treatment is the last resort and that wanton use of chemotherapy is the biggest problem in CLL, I fully recognize the value of chemo when applied properly at the right time. It is the major weapon without which we could not play the game effectively.

For mongrel patients like me, assessing the magnitude of the disease is an enormous challenge, which is why I had so much material for this post. For the record, I have concluded that my disease is on the good end of the bad side, responsive enough to soft-glove therapy that it can be controlled that way, at least for now. My platelets have been trending gently downward (I am unsure of the cause) but are still normal; my HGB is healthy and shows no sign of going south. I feel fine. Lymph nodes are numerous and have never, to my knowledge, exceeded 3 cm. And the spleen, which had been 10 cm below the costal margin prior to my just-concluded third course of Rituxan, is currently "not palpabale" according to my doctor. (In the end I decided to stick with Rituxan alone again but to go for eight rounds this time instead of four; that -- and perhaps strenuous exercise to get the drug into all the nooks and crannies of the spleen -- might have had something to do with the good result.)

Ninth, get your facts straight. “Clinical trial” does not mean “panacea” -- it means “experiment.” OR means “overall response” and CR means “complete response,” and neither may have anything to do with the biggie: OS, or “overall survival.” In other words, one may get a deeper response from Treatment A than from Treatment B, but that doesn’t mean you will ultimately live longer. (This may seem counter-intuitive, but it is sometimes true.) And since most CLL treatment regimens are a work in progress, we simply don’t know if they will ultimately translate into a longer, or significantly longer, OS -- one that might justify the risks associated with their toxicity. (Nor do we know how the track record for single-agent Rituxan will turn out.) That means we are left to make educated guesses. In few other diseases are the choices and timing so tricky. The working title for this post was "The game from hell," and this is an example of why I think the name is appropriate.

Tenth, triple-check everything. Blood labs make mistakes. Doctors get brain fugues. Hell, some patients are even misdiagnosed. And things can evolve: CD 38 can change over time, as can chromosomal abnormalities as detected by FISH test. Last year’s test may not hold true for today. Finally, remember the immortal words of Ernie Hines, the managing editor at a newspaper where I once worked: “You know what happens when you ASSUME something? You make an ASS out of U and ME.” Corny but true. (When the nurse brings the clear bag to the IV pole, I make sure the bag says “Rituxan.” The spirit of Ernie Hines is there, saying, “Do you know how many medical accidents happen every year?”)

Eleventh, before making a big move, consult with others. Now is not the time to get tunnel vision. Get a second or third opinion from a doctor. Talk about your options with fellow patients, or even with a wise friend who may not be an expert on the subject. There are a lot of people out there, in groups such as ACOR and in places such as CLL Topics, who can offer insights and tips. They can’t decide for you, but they can give you some things to think about. Despite your best efforts, you may have missed something that matters. The experiences and insights of others will help you understand the landscape better. The ACOR archives are valuable as well, since you can look up the experiences other patients have had with the same treatment you are considering.

Which brings us to twelve: Follow your own instincts. By that I mean: do not rely on what anyone tells you -- be it Dr. Keating, Dr. Hamblin, Chaya Venkat, or internet bloggers -- as being the immutable truth. Advice, counsel, considered opinions: yes. The word of God: no. The experts often differ (and I am not including myself in that group). You have no choice but to assume the responsibility for making the final decision yourself. So embrace it. Since you have to play the game, play it with all the power and insight that you can. And when making a move in the game, make sure you are ready, that you have your game on, that you’re warmed up and prepared. When you lift your hand to make that move, make sure that it truly feels right. Whatever happens next, however your opponent reacts, you will be at peace with your decision. That, my friends, is invaluable, for I believe your heart has to be in the game to win it.

RESOURCES

Testing packages for IgVH mutational status, CD 38, ZAP-70, and FISH are now readily available to patients worldwide at Quest Diagnostics. (UPDATE: As readers will find as they continue forward with the blog, I believe Quest's ZAP-70 test is currently unreliable -- September 22, 2007.)

The NCI working group guidelines are, according to Dr. Hamblin, currently being revised. The soon-to-be-outdated ones are available here as a PDF:

National Cancer Institute-Sponsored Working Group Guidelines for CLL (1996)

This PDF from 2003, written by Mayo Clinic doctors Tait Shanafelt, Susan Geyer, and Neil Kay is more up to date:

Prognosis at Diagnosis: Biologic Insights Into Clinical Practice for Patients with CLL

From the just-completed ASH conference, by Dr. Michel Hallek:

CLL: First-line Treatment

Treatment issues for those who are becoming hard to treat, by Dr. John Gribben, from the 2005 ASH conference:

Salvage Therapy for CLL and the Role of Stem-Cell Transplantation

Finally, there is much information at CLL Topics about single-agent Rituxan as the basis for first-line treatment. While not especially popular with the medical establishment -- you will not find it touted in the references above -- it makes a great deal of sense to any number of patients, including myself. This is a perfect example of where I would argue that it may pay to ignore the conventional wisdom.

Site search of CLL Topics under "single agent Rituxan"

Site search of CLL Topics under "Harvey" (Rituxan-based "immunotherapy for a difficult case")

Riding the curve

It’s the new year, and I think it’s appropriate to start it with a message of hope and resolve for all CLL patients. This includes those with the tougher road ahead, such as younger people like myself, and those who lack sterling prognostic indicators. So here goes . . .

There are three things I know about my health, and all else is pure conjecture:

I have cancer.
I am going to die.
I may not die of cancer.

A lot of people do not make the final connection. I recall a post on the internet by an otherwise erudite CLL patient who said, “Well, at least we know what we’re going to die of.”

That, my friends, is stinkin’ thinkin’, as Al Franken’s “Stuart Smalley” character used to say. There is plenty of evidence that CLL is not inevitably fatal. And as treatments improve, so will the odds. Various reports say that somewhere between one third and one half of us will survive it and go on to die of the usual stuff: flying anvils, using portable toilets at county fairs, and breath-sucking cats. (And remember that those CLL survival reports are based on older data, from an era of less effective treatments that were applied without today’s improved prognostics and risk-based thinking.)

Yet society still tends to think most cancer patients are doomed. This attitude permeates into the medical establishment as well and perhaps accounts for the rather callous way in which some patients can find themselves treated. Many CLL patients subconsciously accept this misjudgment as a verdict on their condition, and therefore they develop a certain tunnel vision when it comes to treatment: If it helps me today -- no matter what the side effects may mean for my future treatment prospects -- then that’s good, because I probably won’t live that much longer anyway. After all, I have an incurable cancer. Why worry about ten or twenty years from now?

Why worry? Because expectations, and the decisions that flow from them, can make all the difference to your survival. Lower your expectations, and you can expect less in terms of results.

In his book Love, Medicine, and Miracles, Dr. Bernie Siegel describes the three types of cancer patients he has encountered: The first group, around 10 to 15 percent, actually want to die. Their diagnosis comes as some sort of relief, and it usually becomes a self-fulfilling prophecy.

The second group, around 70 percent, would like to live but don’t really want to be bothered with doing everything possible to figure out how. They’ll dutifully do what the doctor says, but they won’t ask many questions, and they won’t go looking on their own for information about their disease and how to treat it. They also won’t make changes, such as learning to cope with stress or giving up bad habits, that could increase their chances of living a longer life. This might be described as the couch potato method of dealing with a medical crisis.

The third group of 10 to 15 percent are what Siegel calls “exceptional” cancer patients. These are the people who raise their hands when he asks, “Do you want to live to be 100?” They have high expectations for themselves, and they have high standards for their medical caregivers to meet. They have a take-charge attitude, want to know everything about their disease, and aren’t afraid to confront doctors, nurses, health insurance companies, etc. when necessary. They also try to come to grips, emotionally and spiritually, with their situation, to find new energies and coping skills that can turn a lemon into lemonade. And here’s their reward: According to Siegel, studies show that these sorts actually do better in the fight against cancer. Treatments work better, and they live longer.

In a recent article in The New York Times, the son of the late author Susan Sontag described her battle with breast cancer in the 1970s:

During the two years of chemotherapy she underwent in the mid-1970's to treat her first cancer - Stage 4 breast cancer that had spread into 31 of her lymph nodes - she managed to publish a book on photography and, a year later, her book "Illness as Metaphor." That time, she had beaten the odds. William Cahan, then her principal doctor at Memorial Sloan-Kettering Cancer Center in New York, told me at the time that he saw virtually no hope. (Those were the days when doctors often told patients' relatives things they did not disclose to the patients themselves.) But as her friend Dr. Jerome Groopman, chief of experimental medicine at the Beth Israel Deaconess Medical Center in Boston, told me a few months after her death: "The statistics only get you so far. There are always people at the tail of the curve. They survive, miraculously, like your mother with breast cancer. Her prognosis was horrific. She said: 'No, I'm too young and stubborn. I want to go for it"' - meaning treatment. "Statistically, she should have died. But she didn't. She was at the tail of that curve."

So how do you get to the tail of the curve? Raising your expectations is a good way to start. If our struggle with CLL is a long, drawn-out fight, then let us remember that morale is a factor in war. It is those who expect to win that often do, and not because their expectations magically make them invincible. It is because they have qualities that give legitimate rise to their optimism: bravery, tenacity, patience, the skill to acquire good intelligence about the enemy, and an ability to come up with the best strategy and tactics. Of course, adequate weaponry helps. And luck, too, is part of the picture.

My guess is that someone reading this post –- or maybe two people, or three, or four, and perhaps even more -– will confound all those with lowered expectations and be at the tail of the curve.

It could be you.