Doctors are from Mercury, Patients are from Uranus

John Gray is the author of Men are from Mars, Women are from Venus and innumerable sequels. He has made a mint trying to explain the differences in the way men and women think, which is one of the oldest conundrums in civilization.

There is a similar mind-bender, almost as ancient, and it may as well be entitled Doctors are from Mercury, Patients are from Uranus. (I have given doctors Mercury, as the Roman God’s caduceus or wand, at right, has been adopted as a medical symbol. I have given patients Uranus, since patients can often be a pain in the nether regions, and often ought to be for their own good).

Most patients are, quite simply, mystified by how doctors think. But coming to an understanding of how this process unfolds (when it unfolds) is crucial to developing a good relationship with one’s doctor, and to knowing if the doctor seems to be doing what’s best. Here, in our corner of cyberspace, we can pick up some clues by reading the medical commentaries of bloggers Dr. Vance Esler and Dr. Terry Hamblin (links at right). In the world at large, one hem/onc who has made a valiant attempt at explaining what goes inside the minds of medicine is Dr. Jerome Groopman, whose book Anatomy of Hope is certainly a good read.

Now Groopman has written a piece for the latest issue of The New Yorker entitled How doctors think. Not that we patients are going to come to a miraculous, Eureka-like moment anytime soon, but it’s worth a look, as it helps demystify the process a little bit more. It can be read in its entirety here.

Groopman discusses the findings of Pat Croskerry, a physician who has written a scholarly article entitled Achieving Quality in Clinical Decision Making: Cognitive Strategies and Detection of Bias.

Croskerry has been trying to figure out why otherwise intelligent doctors misdiagnose things, which research suggests occurs in about 15% of cases, but which Croskerry thinks is “significantly higher.”

“He believes that many misdiagnoses are the result of readily identifiable — and often preventable — errors in thinking,” Groopman writes.

For patients with chronic lymphocytic leukemia, misdiagnosis is rare (but not unheard of). Our main concern are the subsequent decisions doctors make -- when and how to treat, how to deal with related conditions such as anemia and ITP. These decisions can, in fact, be crucial to our survival.

Groopman has some insights into why doctors sometimes screw up. Among these are:

“Doctors make such errors when their thinking is overly influenced by what is typically true; they fail to consider possibilities that contradict their mental templates of a disease, and thus attribute symptoms to the wrong cause.”

That’s a biggie in CLL. Doctors with an unbending, outdated idea of what is “typically true,” are like bulls in china shops. CLL is by definition heterogeneous, which means it varies from patient to patient. A one-size-fits-all approach based upon the idea that CLL is an old man’s disease that doesn’t actually kill anyone does much more harm than good.

A second problem, Groopman writes, is that “Doctors can also make mistakes when their judgments about a patient are unconsciously influenced by the symptoms and illnesses of patients they have just seen.”

Read: Last CLL patient seen, or last one treated, or the one that sticks in the mind like peanut butter to the roof of the mouth. My first hem/onc, Dr. Lippencot, was forever telling me about the one patient she had who had been using fludarabine every two years for ten years and was “still going strong.” I am happy for that patient, but the results would not necessarily have translated to me.

Groopman goes on to write about a side of the issue that I hadn’t thought about:

“ . . . the errors that doctors make because of their feelings for a patient can be just as significant. We all want to believe that our physician likes us and is moved by our plight. Doctors, in turn, are encouraged to develop positive feelings for their patients; caring is generally held to be the cornerstone of humanistic medicine. Sometimes, however, a doctor’s impulse to protect a patient he likes or admires can adversely affect his judgment.”

Well, in today’s era of ten-minute office visits, who knew? Actually, I am aware of some doctor-patient interactions in CLL that have been intense, and that have gone on for a long time, and I can imagine that there is a certain degree of emotional turmoil that goes on beneath the white-coated objectivity. Failure to cope with this is what apparently drove my second hem/onc, Dr. Chopin, out of medicine.

Groopman’s piece also devotes a little space in passing to his experience treating a patient with Adriamycin, aka Doxorubicin, a component in the CHOP therapy that some CLL patients are familiar with:

“Oncologists had nicknamed Adriamycin “the red death,” because of its cranberry color and its toxicity. Not only did it cause severe nausea, vomiting, mouth blisters, and reduced blood counts; repeated doses could injure cardiac muscle and lead to heart failure. Patients had to be monitored closely, since once the heart is damaged there is no good way to restore its pumping capacity.”

Hmmm. One wonders what other nicknames oncologists have for the drugs they use on us. Every profession has its shop talk, of course. Newspaper people are among the worst offenders; I don’t recall every shorthand expression we used in the newsroom, although I do remember us referring to people who died in car fires as “crispy critters.”

At the bottom of our gruff little hearts we did, of course, care. And Groopman did too, though I doubt he went to the patient in question and said “We’re going to treat you with the ‘red death.’”

But that’s what he was thinking.

Roads less traveled

I’m going to see my hem/onc tomorrow for a routine visit, a three-months-after-Rituxan-treatment checkup. There is a certain ritualistic element to the physical examination -- the fingering of the underarm nodes, the tapping on the liver, the measuring of the spleen. The latter is, to me anyway, a mysterious process, not unlike the reading of entrails performed by an ancient priest. There is a certain degree of poking and prodding and tapping and cocking of the ear (to listen through a stethoscope) and it concludes with a solemn pronouncement, usually something like “5 centimeters.”

If someone had told me years ago that this sort of thing would be routine for me, like going to the grocery store, I wouldn’t have believed them. And yet it is. From greeting the receptionists, who I know by name; and the woman who draws the blood, with whom I have made Dracula jokes during Halloween; and the nurse, with whom Marilyn likes to discuss how cold and uncomfortable the office is kept, it is all easily familiar. And therefore not too scary, really. Even the bald-headed women exiting the infusion room and shuffling past the reception desk, stopping to dip their fingers in the candy bowl -- where one can, with sufficient fishing around, usually find Tootsie Rolls -- don’t bother me anymore. These are my people. Cancer, schmancer (as Fran Drescher says in her book of the same name.)

My doctor is the newest component of the experience. Readers may recall that she took over the practice of Dr. Chopin, my previous hem/onc who decided to leave medicine. My new doc -- we’ll call her Dr. Belle -- comes from the South, so she has a certain charm and a slight accent to go with it. I could not ask for a less pedantic, more open-minded physician, and so I am pleased on any number of levels. Visiting Dr. Chopin often required a certain amount of mental preparation and voluminous abstract-printing and organized note-bringing -- for she was forever wanting to treat me with the hard stuff (she had been trained at MD Anderson) and I was forever wanting to avoid it and forever having to make arguments for doing so. Dr. Belle presents no such challenge. She and I are on the same wavelength. She once said something to me about how unfortunate it is that oncologists have to treat people with poisons. She understands that, especially with CLL, there are no magic answers, and that treatment can sometimes do more harm than good.

Alternate universe me

I didn’t always have it so easy. My first hem/onc, Dr. Lippencot, made Dr. Chopin look like a libertine. Readers may recall that her answer to everything, including “What time is it?” and “How about them Diamondbacks?” was “fludarabine.”

Readers also know that I fired Dr. Lippencot and found Dr. Chopin and that I have had 25 infusions of Rituxan since January 2004. It has now been 40 months since my diagnosis at Stage 2 with a swollen spleen, extensive lymphadenopathy, and a lymphocyte count of about 130,000. And for 36 months I have been playing the treatment game, which in my case can be described as “softball with CLL.”

The instant replay: Rituxan has been my sole treatment; my lymph nodes have reached the 3-4 cm range, my spleen has gotten as large as 9 cm below the costal margin; my platelets have slowly declined from the middle to the bottom of the normal range; my hemoglobin has always been normal, and I have had no B symptoms. In 2005, I learned that I am IgVH unmutated; my March 2006 FISH test showed that I had developed the 11q deletion (24%) after having had a “normal” karyotype; and I have maintained a blessed CD 38 negativity which was last measured at 1%.

With those prognostic markers, or at least the first two, there are doctors at big, well-known places who have suggested I look into RF or RFC sooner rather than later. I have avoided this, of course. For as helpful as it might be to know what often happens in unmutated, 11q patients -- conventional wisdom says the disease progresses quickly; remissions are not so long-lived -- it is wrong to assume these results will be true in the same way and in the same time frame for all patients. Heterogeneous disease, heterogeneous results.

And so there are two lessons I have taken to heart from my study and experience with CLL: Treat the patient, not the numbers. Treat when the clinical symptoms demand it, not on the basis of prognostic tests alone.

Prognostics tell us a lot, but they do not tell us everything. Deletion 11q is much bemoaned in the literature, but I know a few patients who are doing quite well with it, and with softball treatments for it. Or, to put it another way: We understand more than we used to about CLL. We have gone from the Dark Ages to the Industrial Revolution. But we have yet to enter the Space Age.

There is no way to know for sure how my Rituxan use has affected the course of my disease. There is no control to my clinical trial of one, no alternate universe in which I did something else and saw the results. But I did get to thinking recently about things doctors wanted me to do that I avoided doing and how they might have affected me. Here’s a rundown of my alternate lives:

Life #1: In October 2003, a month after diagnosis, I followed Dr. Lippencot’s advice and used fludarabine as a single agent. I got an excellent response -- one’s first response to treatment is usually the best -- and entered a fairly deep remission that lasted until the start of 2005. (I had neutropenia and a cough that wouldn’t go away, but I managed to ride it out.) I was retreated with fludarabine and this time with Rituxan added, as Dr. Lippencot had finally gotten around to reading some studies from Ohio State that I had begged her to consider. This remission wasn’t quite as deep as the first, even with the Rituxan, since I was showing some disease resistance to fludarabine. But the remission has been holding up pretty well, and I am only now slowly coming out of it. I will probably need retreatment later this year and there is concern that I may be fludarabine refractory, and I realize that my choices for treatment have narrowed considerably. Oh, and my January 2007 FISH test brought most unpleasant news: deletion 17p, which occurs in 40 – 50% of patients by the time they are fludarabine refractory.

Life #2: In January 2004, I began RFC on Dr. Chopin’s advice. I got an excellent response -- might even have been minimum residual disease (MRD) negative or close had we tested for that. Being youngish and strongish, I sailed through treatment. The hard part came when squamous cell skin cancers struck like lightning and required surgery on my left temple, leaving an ugly scar; there is concern about these cancers recurring, or metastasizing internally, and I have been under the nearly constant care of a dermatologist. Were it not for this, I might have been able to forget I even had CLL, since the remission was so lengthy. But last fall my absolute lymphocyte count began to creep up just a bit. It’s only slightly above normal now, and the nodes in my neck are returning just a little. Treatment in 2007 is likely -- and a repeat of RFC appears to be out, since I can’t expect it to work too well the second time. There’s Campath, but my T cells are already in the pits from the fludarabine, and I can’t risk my skin cancer running amok again, which is what it does with T-cell suppression. Then again, Campath is just about my only option now, since my recent FISH test brought most unpleasant news: deletion 17p, which is pretty much resistant to everything but Campath and steroids.

Life #3: In October 2005, having done Rituxan alone with fewer results over time, I began R + CVP (cyclophosphamide, vincristine, and prednisone) on Dr. Chopin’s advice. It reduced the nodes considerably, but my fingers are still numb as I type this; I worry the peripheral neuropathy from the vincristine may be permanent. The remission, which did more for the nodes than the marrow, was incomplete and lasted about a year; now that that the nodes are coming back Dr. Chopin wants to start RFC. I felt fine before R + CVP and I worry about whether my quality of life will suffer from RFC as well.

Life #4: In May 2006, having done Rituxan alone with fewer results over time, I began RF on the advice of a CLL Research Consortium doctor. I got an OK remission, but having been previously treated with Rituxan, it wasn’t quite as deep as it might have been had I used it as a frontline treatment. I don’t know how long I’ll get out of it -- a 2005 Ohio State study indicates 22 months as the median progression-free survival for unmutated patients with “high risk” cytogenetics (11q and 17p) using RF as a first-time treatment, which I’m not. At any rate, the doctor assures me that after relapse I will be eligible for some interesting clinical trials. In the meantime, the nodes are down. I had a FISH test this month and, thankfully, it showed no 17p deletion, just the old 11q. Maybe I’m being paranoid, but sometimes of late I think I have a sort of lumpy feeling in my abdomen. Richter’s Transformation from CLL to large cell lymphoma only occurs in something like 3 – 5% of all patients -- and 12% of patients who have been treated with fludarabine. It can’t happen to me, can it?

The lessons learned

Clearly and simply: Not one of the above treatments would have been to my advantage, so far as I can tell. Here I am with Rituxan, a bit chunky in the neck, but with an excellent quality of life and no burned bridges (though the old wooden Rituxan rope bridge is missing some boards and swaying in the wind a bit). What would these other treatments have done for me, besides creating some toxic side effects and disease resistance to drugs?

They might have made me feel better for awhile, with a normal lymphocyte count and no nodes to look at in the mirror. (This emotional high might have continued until I began to relapse, which is when the sudden realization that I had fewer treatment choices ahead of me might have hit me on the head, causing a Homer Simpson-like response, namely “D’oh!”)

They would have “bought me time” that, it turns out, I have purchased at a much cheaper cost.

(Indeed, since marrow impaction has not been an issue for me up to this point, I am amazed that chemo has been pushed at me as much as it has. How much of that was quality thinking on the part of my doctors, how much of it was a reflex action?)

Have I taken a risk by not getting a thorough housecleaning of lymphocytes from my system by chemotherapy, by barely holding my CLL in check (if that) by using a low-tox, rather ineffective agent?

Yes, but it is a small risk compared to chemotherapy. Strange complications from untreated (or minimally-treated) CLL can and do happen, but they are uncommon. For example, Dr. Lippencot’s fear that a lymph node would cut off a bile duct to a kidney is, it turns out, almost all hat and no cattle. But I did finally hear, last year, about a case where this happened. (The patient had chemo and his kidney was saved.) So allowing a lot of disease to mill around the body has its risks. Another one is clonal evolution -- doing nothing can still net you a 17p deletion, for example. But there's no reason to increase your chances of such an occurrence if you don't have to.

And the fact is, chemo increases the likelihood of a whole lot of bad mojo. The negatives of chemotherapy and precipitous treatment have been reported, demonstrated, and nailed-down. Is it worth risking burned bridges, a 17p deletion, Richter’s Transformation, pneumonia, rampant autoimmune disorders, pulmonary failure, and God knows what else unless one absolutely has to?

Alternate universe me says “no.”

Rituxan roulette

And so, on Monday, I return to my hem/onc for a routine visit and no doubt a routine discussion of when to again use boring old Rituxan, which gives half-assed remissions but allows me to keep my whole ass intact.

I have been thinking about Rituxan dosing of late, and it seems like nobody knows what the optimal dosage is and what the optimal frequency of dosage is. You’ve got Dr. John Byrd with his 375 mg/m2 three times a week for four weeks and you’ve got Dr. Ron Taylor and his low-dose 30 mg injections. You’ve got doctors who want to do Rituxan maintenance of 375 mg for four weeks every six months or when a patient’s lymphocyte count reaches X number or when Jupiter aligns with Mars; and doctors who do one infusion a month, or every three months. Multiply the number of doctors treating CLL by the number of patients treated and you have as many variables as there are when it comes to Rituxan dosing.

Marilyn and I bought a handmade objet d’art at a thrift store once. It’s called a “mood barometer” and looks a bit like a clock and has two hands, one that says “He” and one that says “She.” The hands can be pointed to any number of semi-amusing places, including “Just a dear,” “Grumpy,” “Ooh-la-la,” and “Hysterical.” (We’ve had them on “Hysterical” for years now.)

I am tempted to make one for Rituxan, with one hand that can be spun. It will land on one of the various dosing choices, and I will go to Dr. Belle and say: “Let’s try this one next time.”

Of course, I am not really skilled at carpentry and I have already experienced some of the dosing variations. But I have not tried low-dose, or regularly-scheduled dosing every three months or six months. I will discuss these options with Dr. Belle, as well as possibly adding steroids to reduce the bothersome pelvic nodes for awhile. I will do some kind of Rituxan treatment in the not too distant future. And I will have my annual FISH test.

And, if the Fates and the FDA allow, I will finally stop using Rituxan at the end of this year or sometime the next.

I will start using HuMax-CD20 instead.

Our long national nightmare

I remember when Gerald Ford became president and told us that “our long national nightmare” -- Watergate -- was over. When America heard those words, it was as close as 200 million people could come to exhaling at once. There was a sense of relief in the land, and during the 1976 Bicentennial celebrations, a renewed sense of hope and even pride. For being a good and decent man at a time when that was exactly what our country needed, Ford deserves the accolades that came his way following his recent passing.

Today, we are in the throes of another long national nightmare that shows little sign of ending soon. It is called the Iraq War, an unnecessary enterprise poorly executed. The result may well be that we are creating a Shiite state in Iraq, one that will ally itself with Iran, which is no friend of American interests. (Who knows, perhaps one day a strongman will emerge in Iraq, perhaps a mullah with dreams of building nuclear weapons against the infidels.) At the very least we have created a base camp for terrorists where there was none before.

It is a nightmare because it didn’t have to happen, and it is not over because whatever will eventually play out in Iraq is only in the middle -- or perhaps even still the early -- stages.

I smelled a rat from the beginning. Like Jerry Ford, who asked that Bob Woodward shield his true feelings about Iraq until after his death, I saw no justification for this war. It seemed precipitous, wrong-headed, unnecessary, avoidable. I know enough about war and politics and history to know that sometimes wars must be fought, and I count among these the invasion of Afghanistan to destroy Al Qaeda and get Bin Laden. Like almost every other American, I was with George W. Bush up to that point.

But I have also read Barbara Tuchman’s The Guns of August, about how the eminently avoidable World War I came to be, and I lived through Vietnam, and so I know when nations make errors in judgment, when leaders are wrong -- when, unlike the case of Jerry Ford, a people are saddled with a head of state who is not the right man (or woman) for the time. What we have in the White House now is an individual whose talents are better suited to being a county commissioner than leader of the Free World. Sometime in 2002, as Bush began to listen to Dick Cheney and his neoconservative pals, and as he began to believe that God had anointed him for this task, the president -- never a student of history -- quite simply lost it.

And so I stood in the rain in March 2003, along with 150 other people, to protest on the eve of the war at an intersection in this small town of ours. We carried candles, and we shielded them from the moisture and the wind. We had many honks of support from passing cars and also a number of hecklers. I have participated in more vigils against the war since, and as time has gone on passersby have honked more and waved more and a cop even briefly flipped on his siren on for us. Last time I was out, no one gave us the finger or yelled about how we were supporting Saddam Hussein.

And part of this nightmare is the feeling of sickness, of sadness, of dread for our troops, our precious young people who have been killed and maimed and scarred in this enterprise -- let alone the tens of thousands of Iraqis who have suffered similar fates. And for those yet to be sent, yet to die, yet to suffer in this madness. It is one thing to play dress-up soldier, another thing to be one in the line of fire. Tim Russert of NBC interviewed a reporter Saturday who spoke to his sources in the Bush Administration and they said what I think we all know: Many of those around Bush, perhaps even the man himself, doubt that his new escalation of the war has all that much chance of working. Maybe -- had Bush listened to Colin Powell rather than Donald Rumsfeld, had he committed overwhelming force at the start and followed up by keeping Jay Garner in charge and not replacing him with Paul Bremer -- maybe, just maybe, it might have worked. But that ship has sailed on the sea of incompetence and naiveté and arrogance that is the Bush Administration.

And now the “surge,” or as Condi Rice calls it, the “augmentation.” The English language, too, is a casualty of war, along with the truth. We do not know for sure what will happen in the coming months, but George W. Bush will do one thing, of that I am certain: He will hand this mess to his successor so that he doesn’t have to face up to the long national nightmare he has set in motion for all of us. Another imperial figure said it long ago: Apres moi, le deluge.

And what of his successor? I have little respect for those who supported the Iraq war resolution. Politics trumped patriotism for many of them, especially the Democrats. Did John Kerry and John Edwards and Hillary Clinton vote “yes” because they believed “yes,” or because they believed it was politically expedient, the popular choice, the right thing to further their careers? And what of the Republicans -- traditionally the party that supposedly likes to avoid foreign entanglements. Did any stand up? Did any bother to demonstrate independence of thought? One gathers that George Bush the Elder may have had his doubts; one knows that Jerry Ford did. People who knew them say that neither Richard Nixon nor Ronald Reagan would have followed the course of Bush the Lesser.

There were a few lonely voices against the war resolution. I remember Robert Byrd, the aging senator from West Virginia, giving long, eloquent talks on the Senate floor, virtually alone in that chamber. He spoke about the meaning of the Constitution, holding a copy of that document in his hand, a prop ignored by those too busy renaming French Fries “Freedom Fries.” Byrd’s voice quavered but his arguments were solid, yet most did not listen.

And I remember Al Gore speaking against the war -- Al Gore, the people's choice in the election of 2000. In The Guns of August and later in The March of Folly, Tuchman demonstrates brilliantly that an accident of history -- be it the assassination of an archduke, or one vote on the US Supreme Court -- is sometimes all it takes to turn the world on its head.

Sometimes I think I will awaken from this nightmare, that the right man will be in the White House, that there is no war in Iraq, that the shared sacrifice President Gore called upon all of us to make after 9-11 is resulting in progress on energy independence (and against global warming), that the wise and skillful use of a nation’s blood and honor has captured Bin Laden, dealt mortal blows to terror, and left us with hope after all. That there is no national nightmare, that it was all a bad dream.

And then I turn on the TV news and I want to cry.

Ten things I’ve learned about CLL

Here is a list of some hopefully useful and occasionally iconoclastic things that I have concluded about chronic lymphocytic leukemia. These are my impressions; your mileage may vary.

1. WBC is overemphasized by patients and local doctors. A CBC is the easiest way to measure the amount of CLL in the blood, but it doesn’t tell the whole story. Unless your absolute lymphocyte count (ALC) doubles in less than six months, and over the course of at least three tests, the number is not especially relevant. A CBC doesn’t measure disease progression in the lymph nodes, spleen, or marrow. CLL is heterogeneous, meaning it doesn’t follow the same rules in everyone: One patient can have a low lymphocyte count and huge nodes or incipient marrow failure, while another can have a high count and not much else going on. Hemoglobin and platelet counts are as useful as the lymphocyte count when trying to gauge disease progression and/or complications. Relying solely on the generic white blood count -- or, more appropriately, the ALC -- is a mistake. Yet this mistake is made all the time, and the planet is apparently rife with doctors who think that when your WBC or ALC reaches a magic number -- often 100,000 -- it is time to treat. There is a mantra to remember: Treat the patient, not the numbers.
   
2. You’re not as healthy as you look. It is easy to assume at diagnosis, when most of us feel healthy, that not much will change. But immunity is degraded in patients with progressing CLL. When you have your first post-diagnosis cold and your lymph nodes swell, you’ll have tangible evidence that something is wrong. As your disease progresses, immunoglobulins will drop and so will resistance to infection. CLL cells can compromise the effectiveness of T cells, and this can lead to squamous cell skin cancers as well as infections. Add the side effects of heavy-duty treatment to this equation and your body can be left at the mercy of almost every bug out there. CLL doesn’t kill patients directly; infections as a result of reduced immunity do, the most common one being pneumonia. Prudent measures -- washing your hands frequently, avoiding sick people, wearing a hat and sunscreen -- should not be scoffed at. You have to help yourself stay well; what you once took for granted is now something you have to work at. So get in touch with your inner Adrian Monk (well, at least a little). You don’t have to live in a bubble -- but avoid unnecessary risks.
3. Chemotherapy costs you. And I don’t mean financially, though it may do that, too. Chemo won’t cure you. It will knock the disease back -- perhaps a little, perhaps a lot. But it comes with a price: Risking immune suppression that leaves you as fit as an AIDS patient is bad enough; developing disease resistance to drugs and giving rise to aggressive, 17p-deleted CLL clones are tragic consequences. Whether your hair falls out or not should be the least of your worries. On some level, using chemo is robbing Peter to pay Paul. That is why it should not be used until there really is no other alternative. This is especially true of fludarabine, which is the bulwark of CLL therapy in the US, and which has been found to be the source of more and more nasty problems as time has gone on. . . . Now don’t get me wrong: Chemo can add years to our lives. It is better than the alternative. When the disease gets to a certain point, we have no choice. The more the disease screws up the body, the greater the risk we need to take to control it. But chemo is not a panacea. It is a necessary evil -- and I use that phrase carefully and intentionally.
4. 4 + 1 = 5 and so does 3 + 2. A new paper points out the importance of second-line therapy in overall survival in CLL. Why are patients who start with chlorambucil (CB) living as long or longer than those starting with fludarabine? CB users respond better the second time they are treated because they develop less disease resistance as a result of their first treatment. So the math is simple: Get a big bang at the start and a small bang the second time = 5. A less stellar response the first time and a comparatively larger one the second also = 5, maybe even 6. The question is, is there a way to stagger treatments so that you reach 7 or more? This is what I’m trying to do with single-agent Rituxan. Wish me luck.
5. Cluelessness is the rule rather than the exception. In a disease where the cause has not been found, and about which the experts disagree (sometimes vehemently), and in which there are no long-term survival studies of the most popular therapies, and which is heterogeneous and quirky to boot, it’s all a guessing game. If there was one obvious approach when watch and wait ends, one consensus choice for treatment, then we’d all be doing it. But there’s not. For Type A personalities who like everything logical and organized, coping with CLL is especially nightmarish. There is an incredible amount of guessing involved, and that starts at the top. Four big-name doctors have now seen my charts; each one had a different suggestion as to what I should do. My experience is not uncommon. . . . Still, there are some tools you can use so that your guesses are educated: It is becoming increasingly clear that knowing your IgVH mutational status, FISH, and CD 38 test results can offer a pretty good idea of what you’re dealing with. (Forget ZAP-70 as done by commercial labs -- until they work out the kinks, the test isn't worth much unless it is conducted at a major research institution.) So have your tests done, consult the best white-coated prognosticators you can find, filter the information through your own intuition, and spin the Wheel of Fortune.
6. Your hem/onc is a prognostic factor. Tests are not the only prognostic factors. The quality of your local doctor is a big one. A good hem/onc, especially one that will work with a CLL expert, may mean a longer life for you. A bad one can take years off your life by prescribing treatment too soon, and by suggesting a treatment that may be a bad choice. Had I followed my first hem/onc’s advice, I would probably be fludarabine-refractory by now, with little to show for it. Dodging well-intentioned bullets from local docs can become a full-time job. But this is one prognostic factor that you can control, thankfully.
7. There is one kind of CLL to avoid like the plague and any of us can get it. I am talking about CLL in which the clone with the 17p (aka p53) deletion predominates. It is aggressive, resistant to most treatments, and will require a transplant if you are to survive. Dithering around with softball therapies like single-agent Rituxan will not be of much help (I know this is tempting and I support this approach in many cases, but if I developed 17p-deleted CLL I would accept the inevitability of a transplant and bite the bullet, chemo-wise, to give it the best chance of success). Some patients, usually IgVH unmutated ones, will develop this deletion through no fault of their own. But many will develop it as a result of chemotherapy that kills off lesser CLL clones and leaves the 17p-deleted with your body to itself. These therapies include fludarabine and the alkalytors (chlorambucil, cyclophosphamide). There is no guarantee that a given course of one of these drugs will cause this to happen, but you cannot use them without risking it. Chancing 17p raises the bar enormously when it comes to deciding on treatment, as far as I am concerned, and I think this risk is underemphasized by doctors and in patient considerations that I see on the internet.
8. Santa moves slowly. There are lots of promising ideas for treating CLL. Until they are tried, tested, and approved, they are no more useful to you than unicorns. The treatment toolbox is the one in front of you today (unless you qualify for a clinical trial, and keep in mind that trials do not guarantee success.) New items may appear in the toolbox one day soon, especially those in Phase III trials that show good results and have fast-track status from the FDA. But theories won’t relieve your symptoms. If you can hold out, do it. But expect the wait to be longer than you want, or expect.
9. CLL is not the world. Life goes on. Bunnies hop, the sun rises, flowers bloom. Pay attention to those things, and to those you love. They have their own journeys, their own needs, even their own health issues. You can feel better by focusing on others. Absorb your CLL experience into the larger context of your life, not the other way around.
10. Statistics are general but you are an individual. There are always people who do better than the bell curve, and those who do worse. Some get lucky, others are unlucky, Some work with good doctors, educate themselves, and make some good guesses. Others follow bad advice, stick their heads in the sand, and hope for the best. Neither approach comes with a guarantee of success or failure, but it can’t hurt to stack the odds in your favor as best you can. On patient forums I see this question asked: “How long do I have to live?” Well, to paraphrase John F. Kennedy: “Ask not how long you have to live. Ask how you can help yourself to live longer.”

In the near future, I’ll provide a list of suggestions for how you may be able to do that.