CLL Diary in the news, sort of

CLL Diary has gotten a couple of nice write-ups recently. It is occasionally reassuring to know that while I can blather on endlessly, I am not blathering on uselessly.

CR, the magazine of the American Association for Cancer Research, features this blog in its Spring 2007 issue. CR profiles a different patient blog in every issue, and writer Alanna Kennedy somehow managed to stumble across mine. The article talks about how I use humor to cope with leukemia and provides an excerpt from The President's Club, a piece in which I complained that us regular chemo customers -- people with chronic diseases -- ought to get the royal treatment, similar to what airlines and casinos do for their best customers. If you follow the link and read it, do read the comments also -- I managed to snag a lousy free hotel room upgrade, but one of the commenters got an even better deal.

CR, which celebrates its first anniversary with this issue, is billed as “a magazine about people and progress in cancer.” They sent me four back issues and I can say that it’s quite well done, with an excellent selection of subject matter that covers both the science of cancer and the experience of coping with it. And I am not just saying this because they did a story on my blog. It’s more reflective and less full of obvious entry-level tips than some similar magazines.

CLL Diary also got a nice mention in Family Practice Management, a publication of the American Academy of Family Physicians. An article Family Practice Meets the Blogosphere reassures physicians that blogs might just be a good thing. The author uses this blog as an example of the good kind of patient blog, not the crazy kind, and says of me, “His thoughtful entries examine the frustrations of the disease and the uncertainties of medicine. His blog site includes links to other CLL blogs, online support groups and sources of medical information.”

I may go crazy at some point in the future, of course, so these articles will have to serve as evidence in any sanity hearing that may come up at that time. Once I go off the deep end, I will probably adopt every stray cat in my zip code and let the yard turn into a jungle. I can see myself now, sitting on my decaying porch, paper bag wrapped around a bottle of pinot noir, meowing back at the cats while Marilyn decorates all of them with stick-on Christmas bows while sipping sherry. The fact that this sounds at all appealing means I really need a vacation.

This is the end of the innocence

Remember when the days were long
And rolled beneath a deep blue sky
Didn’t have a care in the world . . .
But this is the end
This is the end of the innocence
-- Don Henley

"CLL is a long journey," Dr. John Byrd told me when I saw him at Ohio State University last June. While there is maddening uncertainty surrounding disease progression, the meaning of prognostic tests, the effectiveness of treatment, and pretty much everything else about chronic lymphocytic leukemia, Dr. Byrd put his finger on the one thing we can count on: It is a long journey.

And like any journey, it has a beginning, a middle, and an end. I have now reached the middle of mine, and so have many of my friends. People who were, a few years ago, rather healthy and relatively unbothered by their disease, are now sicker, facing more challenges, and using or thinking about using drugs they swore to avoid until they had no choice. For many, the "break glass in case of emergency" moment has arrived.

I am not there yet, but I am getting closer, and I am less afraid of shattering the glass than I used to be.

Back in ancient times -- the fall of 2003, when I was diagnosed -- having CLL was like having an invisible rabbit for a companion. I knew it was there, but no one else could see it, and I tended to ignore it as well. It didn’t seem to matter much, or to do much. Despite the abnormal white count and the presence of some swollen lymph nodes, my immune system worked pretty well. My hemoglobin and platelets were smack in the middle of normal, and I wasn’t getting any sicker than I had before my diagnosis. It was like having a hobby cancer, one that could be nicely tended and that didn’t do anything really bad, and which therefore didn’t seem too significant.

And so the world seemed full of possibilities when it came to treating it, starting with herbs and supplements. EGCG, which I consumed in some fairly massive quantities, held promise. I downed resveratrol in both its encapsulated and more tasty liquid red form. I read that sugar fed cancer and so I quit eating sugar entirely for awhile, until I was blindsided by a piece of raspberry pie on the coast of Maine. I dabbled in supportive drugs, such as cimetidine and singulair, which were supposed to poke at the CLL and keep its growth in check. I recall now with some amusement making an EGCG salve that was orange in color and slathering it on myself before hopping on the treadmill, hoping it would absorb into the lymph nodes, and leaving a trail of orange sweat behind me when I was done. I experimented with almost any tweak that looked as if it held some promise, and like so many patients before and since, I believed that some of these things might really make a difference. Save EGCG in some lucky cases, I am now skeptical that these approaches matter much, at least in situations like mine.

Rituxan, to which I responded enormously well the first time out, looked like something of a miracle drug -- able to keep the disease at bay without apparent serious cost. That was the deal: softball ways to achieve hardball rewards. And I had friends who were doing this, and for a time it seemed as if it would work indefinitely and CLL would continue to be an afterthought, un lapin invisible. Some other friends opted for chemotherapy in one form or another, and it brought them deep and seemingly durable remissions, and the general sense I had was that "my CLL generation" was none the worse for wear.

And then, time passed, and I learned -- "we" learned -- some things about the nasty underside of the disease. The way it acts in the beginning is not necessarily the way it acts later on. This is because it progresses, especially if one develops an 11q or 17p deletion, and this clonal evolution tends to occur the longer one has had CLL. The disease comes back after treatment, and is harder to treat as effectively the second time, and the third time, and the fourth time, especially if the clones grow more aggressive. One can develop autoimmune problems, such as AIHA or ITP or skin reactions, that are, on a day to day basis, usually worse than the CLL itself. Immunoglobulins drop as sure as the sun sets, and therefore infections occur more frequently, sometimes ones that are hard to shake, even with antibiotics. What we began to learn was that the rabbit was not so invisible after all, and that once it materialized it was not a cute and loveable bunny. Coping with the hobby cancer has now became a full-time job for some of us.

Also, alas -- and "alas" does not do the concept justice -- we have lost friends to the disease or related conditions. People we knew, loved, and respected are now dead. Sometimes we can see, in hindsight, how it came to be, and sometimes we cannot. The sense of loss is great all the same. It is like being in a war and watching your buddy die next to you in a foxhole; you are angry and sad and part of you wonders if that will be your fate, too.

If these things I am writing about seem a little dark to some of you, this is the point at which I need to remind everyone that CLL comes in many forms. The lucky patients are those with genuinely indolent cases -- those who have what might be termed asymptomatic lymphocytosis -- and you might be one of those, and you might be spared from finding that the journey has a middle. My friends and I, we seem to be confronting CLL in all its plumage, and it is this experience that I am trying to describe.

And so, here we are, learning to cope with more stress than we had imagined at the outset of the journey, and with an array of choices for treatment that get no easier to decide upon with time. For some of us, myself included, the idea of a stem cell transplant is no longer out of the question, no longer something so distant as to seem impossible. Indeed, the thought that, despite serious risks, it might just be curative, is welcoming on some level, a huge relief. And so the unthinkable has now entered our thoughts and is part of our daily ritual, the mantra that goes What Will I Do?

If I have learned anything, it is that the rabbit is real and that there is no easy answer when it comes to what to do about it. I take CLL more seriously as its side effects have become more serious. I rely more on my own instincts as I sort through the maze of conflicting advice that expert doctors (and others) provide. I am stronger, braver, and oh so much more tired of it all.

Looking back, I think there is a powerful desire on the part of newly-diagnosed patients to believe the "it’s-the-good-cancer-and-you’ll-die-with-it-not-because-of-it" story that we all hear at the beginning of the journey. For awhile anyway, that illusion is borne out by the disease’s seeming inactivity. And equally, there is a desire on the part of many to believe in The Next Big Thing, usually a drug or treatment that will come along and tame or even cure the disease If Only I Wait Long Enough. In the interim, we parse prognostic test results like fortune tellers reading tea leaves, in the hope that they will tell us our future. But even the best fortune tellers can only reveal so much. Each person’s CLL has a course of its own to play out, animated by factors that we can only guess at. We look to our doctors for reassurance, and they are wont to give it, even when the rabbit is sitting right there, chewing on an oversized carrot and saying "What’s up, Doc?"

The reality, the truth of the matter, is that for many of us, those with progressing CLL, the time comes when the clock starts to run out. We must use the treatment tools that are here today, carefully, and hope for the best.

Some of us pray, too. I am an agnostic, and I pray also.

Friday, bloody Friday

What do you do when your doctor gets fired?

I am about to find out, and it is not something I expected, wanted, or feel like coping with. The past six weeks have been stressful enough without having my horse taken from me in the middle of the CLL-filled, AIHA-ridden, low-immunoglobulin-can-I-get-some-IVIg treatment stream.

What occurred last Friday was a coup, in the best tradition of the Medicis or the Borgias or the Soviets. One minute Alexander Dubcek, president of Czechoslovakia during the 1968 “Prague Spring,” was there in the picture, the next minute he was airbrushed out.

I have written in these pages about my three hematologist/oncologists. Dr. Lippencot, the first, was rigid and unbending in her insistence that I do single-agent fludarabine, so I went looking elsewhere. Dr. Chopin, the second, was open-minded if a little skeptical, but treated me with single-agent Rituxan for two years. She decided to leave medicine; her replacement was Dr. Belle, who for the past year has been my horse, my Dubcek, and a doctor with whom I was very pleased.

Dr. Belle is a slight, younger woman, short, not a commanding presence. I know that in the professional world women are often judged on their looks and stature; it is doubly hard for women who are small or a little pudgy or anything other than Thatcheresque to easily gain the respect of colleagues and coworkers -- and this can include other women, as well as men. And I think we all know by now the truism that a man who stands up for his rights is considered to be assertive, while a woman who does the same is often considered to be a bitch. Whether these sorts of things played a role in Dr. Belle’s eventual fate, I can only speculate.

As I grew to know Dr. Belle, I came to like her and respect her more and more. She is not a CLL expert, but is willing to consult with experts, and to learn. She did not bring a set of unbending judgments to the table, she did not suffer from a God complex, but this did not mean she was “soft.” Behind the sweet Southern exterior was a willingness and a drive to fight for her patients.

I saw this grit last Friday when, unbeknownst to her or to me, I was the last patient she was to see while employed at the oncology group where I have gone for 3 ½ years. My application for IVIg at the neighboring hospital had been rejected because my IGG was 746, just above normal. A new test pegged it at 436, well below normal, and enough to change a “no” to a “yes.” Dr. Belle said she’d have the nurse fax the request over that very afternoon, and she wrote at the bottom of the fax that if this request was not approved she would not hesitate to admit me to the hospital, if that’s what it took to get the IVIg into my veins. She was hoping I’d be able to get it on Monday.

When I left at 1:30 p.m. Friday afternoon, I had no idea that a letter, dated two days prior, and mailed the day before, was starting to arrive in the mailboxes of her patients. This letter informed us all that, effective Friday, the day I saw her, she was no longer associated with the oncology group.

The irony is that, during my appointment with her, I got the impression that she not only liked her job but had definite plans to stay. She talked about “making partner” in another year. This would mean joining the four male doctors in the practice on equal footing. I am certain that she was led to believe one thing would happen when, behind her back, quite the opposite thing was brewing.

And so, perhaps an hour after I left at 1:30 p.m., Dr. Belle probably finally got the news, and was left with a few minutes to clean out her desk. Her patients have been left doctorless, and for those of us in the middle of treatment, this is especially nervewracking. I do not know what compelled the partners to make the choice they did, but I have the sense that it involved personality conflicts more than questions of competence. I am obviously biased, because I liked my doctor and was comfortable with her approach and judgment. And I think the way her dismissal was handled was reprehensible.

And so, my treatment, my file, my life, will now be put in the hands of one of those very people whose method of action I regard as dishonorable. How do I look them in the eye with anything less than contempt? How do I trust such a person with my health care, to make the best decisions, to listen to me and give a damn?

And what are the odds that I will find a doctor who is as simpatico with me as Dr. Belle?

Zero.

Yet I have to go in tomorrow and fight for someone to make sure I get my IVIg, when I don’t even know who my doctor is. It will be chaotic, patients coming to see a doctor who’s no longer there, patients getting chemotherapy on the orders of a doctor who’s been fired.

And I, of course, am one of them. Who will listen to me when I suggest things like low-dose Rituxan, who will read the abstracts and studies I bring in, who will take the time to pore over Dr. Terry Hamblin’s three-part series “What is the aim of treatment?,” which I must once again print out and hand to a strange doctor in the hope that some of it might sink in?

I am left to reinvent the wheel at a time when my coping skills have been already been taxed to their limit. I do not know what will happen to my treatment program, and I do not know where to turn when it comes to finding another doctor. There are 42 hem/oncs on my health plan, and I am in no mood to go doctor shopping starting with the “A‘s.”

I do have Dr. Belle’s e-mail address. She established a Yahoo account so patients could communicate with her, which was an innovation in an office where giving work e-mail addresses to patients is evidently verboten. I will write to her and tell her how upset I am that this happened, and I will ask her to let me know if she joins another practice, or sets up shop on her own.

And I will tell her that, if letters of recommendation from patients mean anything when doctors apply for work, I will be more than happy to write one. They probably don’t count, but it’s all I can think of to do.

It will be an interesting week, and I am not looking forward to it.

UPDATE

I made contact with Dr. Belle. Turns out she found out about her dismissal from a patient who saw her Friday morning, then went home and read the letter, and then called Dr. Belle that afternoon to ask what was going on. Talk about a chickenshit way to handle a firing!

Dr. Belle will resume practice, somewhere, somehow, in the next few months, so I will be able to see her again. In the meantime she is referring her patients to another office, where I have made an appointment. They've been inundated with Dr. Belle refugees, er patients. While I am not certain I will adopt the new office, I'll at least check it out.

One reason is that it is simply hard, emotionally, to be in the old one. The atmosphere when I went in Monday for my Rituxan was funereal. Most of the staff was shocked and unhappy about what had happened. As much as they felt free to talk, the didn't see it coming, didn't think it was handled right, and didn't think it was a good idea to begin with. When Marilyn told one staffer that we were thinking of switching offices, the employee replied, under her breath, "I don't blame you."

The hardest thing, for me, is imagining myself in an examination room having to be pleasant to one of the underhanded partners. I'll do it if I have to -- ultimately, the head must rule the heart if it is in the best interest of my treatment. But if this new office works out, I may not be put in that position. In the meantime, I wonder how long I can continue getting low-dose Rituxan without actually seeing a doctor.


It's always something. If it's not one thing, it's another -- Roseanne Rosannadanna

Low-dose Rituxan

As readers of this blog know by now, I am currently being treated with low-dose Rituxan, 20 mg/m2, every Monday, Wednesday, and Friday. The plan calls for this to continue until my white blood count is normalized or until I reach a plateau at which Rituxan no longer appears to be effective.

That “m2,” by the way, stands for per “meter squared,” which means the dosage is calibrated to my body surface area, a calculation involving my weight and height. When they hook the bag up to the IV pole, it actually contains 42 mg of rituximab. The standard dosage would be 375 mg/m2, which I have had often in the past, and which usually translated to about 750 - 780 mg per bag once my body mass was factored in. So, even a math dunce like me can see that it will take somewhere on the order of 18 infusions of low-dose Rituxan -- six weeks’ worth -- to equal one dose of standard-strength mouse juice. I’ve done five weeks so far.

If less can achieve the same or better results as more, there are obvious advantages to using less. These include reducing the possibility of creating disease resistance to the drug, fewer infusion reactions, and reduced chances of unwanted side effects such as delayed-onset neutropenia and potentially dangerous skin problems. Plus, depending upon how much you and your insurance are paying, it costs a lot less. The only loser is the manufacturer, Genentech.

On the other hand, it is important to remember that Rituxan is still Rituxan, and that its use as a single agent is not a panacea for chronic lymphocytic leukemia. Rituxan-induced remissions are not terribly deep nor durable. There is no reason to think that low-dose Rituxan remissions will last any longer than those at standard dose. As one doctor put it to me, “I have used low-dose rituximab a couple of times with no clear evidence of long term effect yet.”

Early word on low-dose Rituxan’s effectiveness

Still, if Rituxan is your poison, low-dose -- hereafter referred to as LDR -- may be worth considering. Here is the early data, some anecdotal, some from pilot studies:

One patient has posted her experience online, pointing out that her absolute lymphocyte count (ALC) dropped from 137k to 4.6k after eight weeks of LDR at 30 mg, given intravenously three times a week. She had used standard-dose Rituxan in the past.

A pilot study conducted by Dr. Ron Taylor (photo below) and other researchers at the University of Virginia, during which patients were given LDR by IV three times a week over four weeks, showed results ranging from stable disease to complete response (link at end of post, along with lots of other links). Not surprisingly, the complete responses were achieved in patients with the highest levels of CD20, and both were, it is interesting to note, 17p-deleted cases.

Another patient experience, detailed in a CLL Topics Alert, shows the more middling, “stable disease” end of LDR response -- the patient’s counts had been rising, almost doubled in the month before LDR began, and were stalled by LDR, but not reduced. After four weeks of subcutaneous injection of LDR, 20 mg three times a week, his ALC went from 44.7 to 46.0. Are his results a matter of his state of disease, his CD20 expression, or could the sub-Q method of administration be less effective than IV?

There is now a clinical trial underway, using a flat 20 mg of LDR, to help answer the question of LDR’s effectiveness in a larger cohort of patients than Dr. Taylor’s original pilot study. After all, the proof of any theory is in the patient pudding. The bottom line is not how elegant the theory, but how concrete the result. Your donations to CLL Topics are helping fund Dr. Taylor’s laboratory analysis of the trial data.

It should be noted that LDR can also be accompanied by nasty infusion reactions, so adequate premedication (usually Benadryl, Tagamet, Tylenol, and a steroid such as Solu-Cortef to reduce the inflammatory response) is a must. I know of one patient whose first infusion of 20 mg/m2 was a near-disaster, exacerbated by her doctor’s refusal to adequately premedicate her, which borders on malpractice. I do my LDR infusions with no premeds, but I have had standard-dose Rituxan 25 times in the past, so I know my limits and my tolerance. Even then, when the nurse ran the bag through a little too quickly one time, I got a chill and broke out in a sweat. LDR is not a license to forget about precautionary measures, and this also includes pre-treatment allopurinol and drinking lots of water, both of which help protect the kidneys from tumor lysis, which can happen when millions of cells die at once.

My experience with LDR

In my case, so far, LDR is bringing down the white count. As you may recall, I also had 72 mg of methylprednisolone daily for a week, which did an excellent job of debulking me, and which has been gradually tapered and is now at 4 mg a day. The importance of the steroid in my particular treatment cannot be overemphasized. Its addition to the protocol was triggered by the onset of autoimmune hemolytic anemia (AIHA). The hemolysis soon stopped, and my red counts have since been recovering, slowly but steadily.

One effect the steroid had was pushing CLL cells out of the spleen, nodes, and marrow, doubling my WBC to 364k at one point. Then, almost as quickly as it doubled, it dropped: to 271k after another week, and to 95k after another. LDR was only one factor here, I think. Another is the steroid itself, which has lympholytic (lymphocyte-killing) properties and very likely some synergy with Rituxan. Another significant factor was probably the ramping down and end of an infection that likely had precipitated the AIHA, and which had been driving my white count upward even before the AIHA set in. As any CLL patient who has gotten a cold knows, your count will go up and then down again when the cold is over. My supportive meds -- Bactrim, diflucan, augmentin, and acyclovir -- no doubt had something to do with the end of the infection.

Since my white count fell below 100k, the LDR has been dropping it steadily, from 95k to 81k three weeks ago, from 81k to 67k two weeks ago, and from 67k to 49k last week. At this rate, my count should be normalized in about three weeks. I say “should,” because as we go lower, we encounter a greater chance of reaching a plateau point, where the effectiveness of Rituxan ends and cells shorn of CD 20 begin. (Back in October, when I did standard-dose Rituxan three days a week, that plateau point was 22k, achieved after just five infusions.)

The bottom line today is that the steroid and LDR combination has worked better than I had hoped -- so far. That is the operative phrase: “so far.” The bulk is largely staying off and the count is going down. If I can get a normalized WBC and have reduced the bulk by a substantial amount, it will have been a successful treatment experience.

Whatever the end result -- whether I get as good as I’m hoping, or whether the counts plateau at a higher level -- the question comes up of how durable the result will be. The count is not everything; indeed, in a patient prone to bulkiness like me, it is less important than the nodes. Many patients who have used steroids to debulk report that the nodes come back within a month or so. It will be interesting to see if that happens in my case. The steroid dosage is now so low that it is doing little to hold back activity in the nodes. I have noticed a very minor uptick in one node on the side of my neck, and I get the impression that even as my counts continue to drop with LDR, the nodes will gradually begin their return.

So, I am left to wonder: Where will I be a month after treatment ends? Will the nodes be back to where they were before I started? Will they be a shadow of their former selves, indicating that the treatment has ramped the disease down to a good degree? How long might they be held in check before retreatment is needed?

As we all know in CLL, there are no easy answers, and different patients get different results with the same protocol. As the Romans used to say, experientia docet -- experience teaches.

Planning my encore

So, what do I do for an encore? It depends, to a great extent, on how my treatment plays out. But doing nothing until the disease gets as bad as it was before I started would not be wise. Those days are over. In my case, the “just let it go until you hit the wall” approach brings with it infections and AIHA, which are not worth the risk. Getting mashed against the wall like a bug on a windshield is messy and unpleasant, to say the least.

One option is to do another cycle, as it were, perhaps giving my body a month’s rest and then using a four-day course of steroids to debulk again, followed by more LDR. Chemotherapy often runs in cycles of up to six go-arounds of treatment. Would more cycles benefit me? Would I be able to gradually erode the disease through this method?

If it works, then I might be able to adopt a new “low-tox” route of disease maintenance: Repeat this process every so often -- say every four months -- to keep the disease in check. Add periodic IVIG to boost my immunity against infections. Take maintenance acyclovir, one 400 mg pill a day, to control the herpes virus (my titer for this was high recently). Acyclovir may also help against the Epstein-Barr virus, which I know I have floating around in my system, as I had infectious mononucleosis as a child. An EBV titer test has been taken, and the results are pending.

Another option, depending upon how deep a remission I get, is to consider following this treatment with Campath consolidation. Having unmutated, 11q-deleted CLL means the disease will return faster than it would in many other patients. Would using Campath at this point in my CLL career be worth the risks that accompany this important, highly immunosuppressive monoclonal antibody? I will be studying the ins and outs of Campath over the next month or two. Stay tuned.

What about other chemo drugs?

My thought on FCR is that it is still best saved for transplant conditioning, by which time it will probably be FCH (as in HuMax CD20) and likely a more effective regimen than FCR. While I have accepted the likelihood of having a transplant at some point, I see no survival advantage to doing it now, as opposed to putting it off for as long as reasonably possible. I am only 50 and have a ten-year window to accomplish the task. And so far, by the way, I have no signs of marrow failure.

Chlorambucil is another option, as is cyclophosphamide, which is considered to level the playing field for 11q patients. But I would have to investigate how much one of these drugs would meaningfully add to what I am already doing.

Meanwhile, back at low-dose Rituxan Ranch

The whole theory behind low-dose Rituxan has to do with CD20 shaving and complement, a subject that Dr. Taylor has been studying for several years. We all know that Rituxan is a man-made antibody that affixes itself to the CD20 “fingers” on B cells. In cancers such as non-Hodgkins lymphoma, where there is a lot of CD20 per B cell, Rituxan works pretty well. In CLL, there are fewer fingers, and therefore it is less effective. (HuMax CD20, Genmab’s new anti-CD20 monoclonal that will probably be on the market in a year or two, requires fewer finger to work well, and may be able to do in CLL what Rituxan does in NHL.)

Briefly, the idea behind CD20 shaving is this: One of the ways in which cell-kill is achieved when Rituxan is used is by complement-dependent cytotoxicity, or CDC. The body’s complement system provides a fundamental level of immunity, and includes those mighty cell-chomping macrophages, which look like something out of a science fiction movie (photo below). In a process called phagocytosis, those macrophages, along with granulocytes, kill “invaders” such as Rituxan-tagged B cells (and innocent little red cells, when things go haywire in AIHA). But they become overwhelmed by the sheer number of Rituxan-B cell complexes when a lot of Rituxan is used (Taylor et al are still trying to define “a lot,” but is appears to be somewhere above 30 mg, definitely above 60 mg, and therefore includes standard-dose Rituxan). At a certain point, rather than killing the cells, the cells are sent to the liver, where they are shorn of their Rituxan-B cell complexes but not killed. In other words, the body has taken a shortcut to solving the problem. Et voila -- what returns to the bloodstream is a B CLL cell, minus its CD20 and any Rituxan that was attached to it. You have now officially shot yourself in the foot, or somewhere worse. Yes, CD20 may grown back over time, but there is no doubt that this process is a setback in treatment that is better off avoided. You don’t want to end up feeling like the cat in the photo at the end of this post.

Complementary medicine

Beyond this, there is evidence that the massive cell-kill process initiated when Rituxan is used also depletes complement. It recovers, but not immediately, rendering diminishing results in the interim. Early in his research, Taylor looked at this end of the problem and asked: What if we give the patient more complement? In a 2002 abstract, Taylor and colleagues concluded: “We suggest that if an anti-tumor mAb such as Rituxan requires robust Complement (C) activation for therapeutic efficacy, then insuring an adequate level of C activity in a patient, by supplementation with either fresh plasma or a purified C component such as C2, may provide an important approach for improving the therapeutic efficacy of a C-fixing mAb.”

This sounds logical, and an abstract presented at ASH in 2005 by Israeli doctors showed that this worked in one patient: a woman who had been through the chemo mill, including fludarabine and cyclophosphamide as well as Rituxan, and who was barely responsive to therapy anymore. Her doctors gave her two units of fresh-frozen plasma followed by 400 mg/m2 of Rituxan on day one, and the same amount of plasma followed by 275 mg/m2 of Rituxan on day two. They described her response as “dramatic,” and this included “marked reduction of lymphadenopathy” and resolution of other symptoms.

“To the best of our knowledge,” the doctors concluded, “this is the first description of a case where successful induction of dramatic and rapid improvement of both clinical and laboratory parameters in a patient with advanced CLL previously resistant to Rituxan-containing chemo-immunotherapy was achieved by combining Rituxan therapy with fresh frozen plasma as a source for complement. This observation has to be verified in additional patients in order to confirm the approach of potentiation of Rituxan effect by providing increased amount of complement in order to augment CDC.”

So, why not go this route? Well, I tried to get my second hem/onc, Dr. Chopin, interested in it back in 2005, and she looked at me like a deer caught in the headlights. The fact is that it is impractical and experimental. Using lower-doses of Rituxan, so that complement does not become overwhelmed in the first place, is far more practical, as well as more cost effective.

Non-standard standards

How did 375 mg/m2 get to be the standard dose for Rituxan in CLL? There appears to be some question about this. One suggestion is that this was an arbitrary dose, determined by how much was on hand in an early study and how many patients needed to be treated. Another explanation is that it is based on a pivotal trial of Rituxan in patients with relapsed indolent lymphomas such as low-grade NHL. In this trial, the results published in 1998 by McLaughlin et al of MD Anderson, dosages of 375 mg/m2 once weekly for four weeks were used. This formed the basis for the use of 375 mg/m2 in the 2001 CLL study by Byrd et al -- it is directly cited -- in which patients were given Rituxan three times a week. This was in an effort to make up for the difference in effectiveness, as it were, between CD20 expression in indolent lymphomas and CLL. (Dr. Byrd still uses this protocol, and this is the one I tried last October until a plateau was reached, so the results in my case were rather disappointing.)

The larger point is this: There may not always be a truly logical reason behind the dose-selection of drugs. If the story about arbitrary dosage of Rituxan is true, that certainly raises a red flag. Even if the 375 mg/m2 is based on results in NHL, that may not hold water as a logical step in CLL. Low-dose Rituxan is no less logical than any of the above, and may be supported by better theory. So if it seems “weird,” it is certainly no less “weird” than the “standard.”

Another example is FCR therapy. It appears from reading CLL Topics that the FCR “lite” protocol currently in trial at the University of Pittsburgh may be every bit as effective as the regular-strength FCR protocol pioneered at MD Anderson. One would like to be a fly on the wall at meetings where dosages are determined. Is there a dartboard in the room? Do our famed researchers use “paper, scissors, rock” to decide how much fludarabine to give?

I’d like to think, of course, that the soundest of science is backing these choices, but I have a feeling that educated guesswork is every bit as common. However dosages are determined, the bottom line for us patients could not be more important. Thousands of us CLLers may have been unnecessarily overusing Rituxan for years, until a light bulb went off in Ron Taylor’s head. We shall see, of course, how brightly it shines and where it leads us.

Reading up on LDR

For those who want to examine LDR in more detail, here are some useful links that I have assembled.

Dr. Taylor does a nice job of explaining CD20 shaving in layman’s terms in a short piece he wrote for the UK CLL Support Association entitled Shaving and Rituximab: Targeting the Sharks. Chaya Venkat of CLL Topics does her usual excellent job of translating medicalese into English in the article CD 20 Shaving with Rituxan. An earlier article of Chaya’s, Role of Complement in Rituxan Therapy, is also worth reading and contains the complete abstract of Dr. Taylor’s early work suggesting that the addition of complement to Rituxan may be useful.

Dr. Taylor and colleagues have published three abstracts you might want to read. They are:

Pilot Study of Thrice-Weekly Low-Dose Rituximab (RTX) in Chronic Lymphocytic Leukemia (CLL): Decreased CD20 Loss Via "Shaving" and a Novel Strategy for Enhanced Therapeutic Targeting

A Pilot Study of Thrice-Weekly Low Dose Rituximab (RTX) in the Treatment of Chronic Lymphocytic Leukemia (CLL) Suggests Enhanced Therapeutic Targeting Compared to Standard Dose Regimens

Thrice-Weekly Low-Dose Rituximab Decreases CD20 Loss via Shaving and Promotes Enhanced Targeting in Chronic Lymphocytic Leukemia

Here is the clinical trial now underway at the NIH, which is apparently still recruiting patients, so those of you with a hankering to visit Bethesda, MD may wish to consider it:

Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia

The Israeli abstract -- Successful Induction of a Rapid Improvement of Both Clinical and Laboratory Parameters in a Patient with Advanced CLL by Combining Rituximab with Fresh Frozen Plasma as a Source for Complement. A Novel Therapeutic Approach? -- is only available online by logging into ASH and looking up their 2005 conference. Registration is free and it is abstract #5030.

A lymphomaniac in the White House?

You may have heard by now that former Sen. Fred Thompson, who is considering a run for the Republican nomination for president, has Marginal Zone Lymphoma, for which he has been treated with my favorite mouse cocktail, Rituxan. MZL is described as an “indolent lymphoma,” and here is a report last week from abcnews.com, in blue print:

Thompson, 64, said in a statement that his cancer was initially detected during a routine physical two and a half years ago, and he initially received chemotherapy to treat it.

This means, that for the time being, Thompson has no signs or symptoms of the cancer. Thompson's cancer is also a case of "indolent" lymphoma -- a type of cancer that, while rarely cured, is slow-growing and associated with a much more favorable prognosis.

"I have had no illness from it, or even any symptoms," Thompson said in a statement issued Wednesday. "My life expectancy should not be affected. I am in remission, and it is very treatable with drugs if treatment is needed in the future -- and with no debilitating side effects."

Dr. Bruce Cheson, professor of medicine and head of hematology at Georgetown University Hospital, treated Thompson. He says the senator's prognosis is favorable. "Some lymphoma are very aggressive, but people with slow-growing types, like Sen. Thompson's, often die from natural causes associated with old age, rather than from the disease," Cheson said in a statement, also issued Wednesday.

What Indolent Lymphoma Means

The word "lymphoma" is actually a general term used to describe more than 30 different types of cancer that affect the lymphatic system, all with varying degrees of aggressiveness.

"It really depends on the type of lymphoma you have as to your outlook," said ABC News Medical Editor Dr. Timothy Johnson on ABC News Radio Wednesday morning. In Thompson's case, Johnson said, the fact that he is still in remission after his initial treatment is a positive sign.

"With a very slow-growing, or indolent, as we sometimes call it, form of lymphoma, sometimes in those people you just watch and wait and monitor the situation," said Johnson.

"It sounds like he's got one of those forms of lymphoma that is very slow-growing. Many people with this kind live a normal life span."

Indeed, current figures suggest that patients with indolent lymphoma can generally expect to survive for another seven to 10 years.

However, it is unlikely that Thompson's cancer is completely curable using current treatments. Since most cancer treatments today target fast-growing cells, it's hard for doctors to completely wipe out slow-growing ones.

Chance of Recurrence Remains

Even though Thompson is currently in remission, given the nature of the disease it is possible that the cancer could recur in the years to come. After initial treatment, most patients with this type of cancer have a remission period of between 1.5 and 4 years, after which they will relapse. Doctors will then treat the cancer again, usually with a stronger course of treatment.

Subsequent periods of remission are often shorter than the first. But since these periods are measured on the scale of years, many patients can expect to live for many years after diagnosis -- perhaps eventually dying of old age rather than from the cancer.

This likely means that if Thompson is considering a serious presidential bid, it is unlikely that his cancer will hold him back.

"There's always a chance of recurrence with this, and any kind of lymphoma, at which point it usually can be treated again," Johnson said. "So I think at least for the next few years, he should be physically able to run for president."

Sounds a lot like some cases of chronic lymphocytic leukemia, right? After all, CLL is medically considered to be a low-grade lymphoma.

There was a budding discussion on the ACOR CLL list about the ramifications of having someone with this condition -- our condition -- in the White House. It was posited by a couple of members that disease-related fatigue would be debilitating, and that chemotherapy might lead to “chemo brain.”

I replied thusly:

"I think it is pretty evident that some presidents can have 'chemo brain' without ever having had chemotherapy. There are those who are physically fit and yet who are unfit for office. I would have no problem voting for a candidate with indolent lymphoma, or CLL, whose prognosis indicated that serious complications would be unlikely for at least four years, and who appeared to be mentally sound and had the wisdom and ability to do a good job."

Alas, this discussion has been cut short by the on-duty moderator, who thinks it is about politics, a list no-no, when it really is about the question of whether CLL and its cousins render its victims potentially incompetent to do demanding work. (This rather short-sighted approach is why I do most of my posting at CLL Forum, where there is currently a civil discussion of this very same issue.)

But I think the discussion that began on ACOR deserves to continue, and so I will post about it here, and elaborate a little bit more.

There are indeed people with CLL-related fatigue, and those who need rest during chemotherapy. Not everyone with CLL, or indolent lymphoma, has the energy to run errands, let alone run the country. But an enormous number of patients, probably the vast majority, do have the energy. They have jobs. They raise families. Many have positions of responsibility in all walks of life. The case of the late 60 Minutes newsman Ed Bradley is the most prominent example of someone who maintained a high-powered career with CLL. There are likely other rather well-known CLLers, who keep their disease a secret, fearing it would color perceptions of their competence and ability, leading to diminished opportunities.

This is already the case with Joe and Jane Average, patients who really do face the prospect of employment discrimination if they are honest about their condition. I personally know of people who have been eased out, let go, even fired, following disclosure at work of their CLL diagnosis. Not only is an income at stake for these folks, so, often, is health insurance. (Beyond these practical matters, of course, are issues of vocational fulfillment and self-image.)

In the same way that the American people have come to realize that you can be a woman and hold high office; or be an ethnic minority and hold high office; or be gay and hold high office; or be of a religious minority, such as a Jew or a Mormon, and hold high office; or be in a wheelchair and hold high office; has not the time come for us to realize that you can also have a chronic disease like CLL or indolent lymphoma and do the same? Indeed, having a disease like CLL can broaden one's horizons in a way that might actually serve the country well.

I am not rooting for Fred Thompson to win, since I think we desperately need a break from Republicans. But I am rooting for him to enter the race, which will raise the profile of people like me, as well as the consciousness of the public at large.

Debulking: the amazing photographic evidence

I mentioned recently the rather astonishing debulking effect that methylprednisolone -- being used to treat autoimmune hemolytic anemia -- has had on my chronic lymphocytic leukemia. Sometimes a picture is worth a thousand words, so I am posting two pictures today in lieu of writing 2,000 words.

The top photo is me on February 7, before the AIHA came calling and any treatment was done. Someone was kind enough to say that my thick neck made it look like I had been working out, but the only workout was being done by the CLL, which was ever expanding itself into lymph node masses.

The second photo was taken March 25, a little more than a week after starting treatment with 72 mg of methylprednisolone for the AIHA (and also 20 mg/m2 of low-dose Rituxan three times a week). Who is that man with the neck?

Now, imagine that sort of lymph node impaction throughout my abdomen -- I have no doubt that the bothersome pelvic nodes I have written about in the past were in a similar mass -- and you know why I slimmed down there, too, and no longer need my "maternity clothes." Altogether, I have lost 22 pounds since starting the steroids, which are now tapered to 16 mg daily. (As to the AIHA, I am doing OK but the red counts are still not normalized.)

I hope these photos show what unmutated, 11q-deleted clones of "the good cancer" can do. Often we patients get used to a slow change in our appearance and forget what we looked like before the lymph nodes began to swell. And while this shows what the CLL visibly did, another big part of the story is what it did that I couldn't see -- compromised my immune function, allowing something, probably an infection, to trigger the AIHA.

By the way, I made this note to myself on the third day of methylprednisolone therapy: "After two days of steroid, nodes reduced to about the least since initial (Rituxan) treatment three years ago. Six pounds lost." In other words, the debulking occurred substantially within the first few days of steroid therapy. Today, only two palpable, almond-sized lymph nodes remain in the fleshy area under my jawline, both vastly reduced from before.

The challenge ahead, after recovering fully from the AIHA, is to maintain my slimmer physique by good diet and exercise and to keep the CLL at bay. Seeing the massive bulk that was built up in me, and coping with the hidden consequences of the disease running amok which suddenly came to the fore as AIHA, has caused me to do a little thinking about the possibility of using something a little stronger to solidify my remission.

In the meantime, here are the photos, before and after:

A spring in my step (or the weight loss follies)

This morning’s e-mails contained a spam message titled “End the annoying obesity now.” I had to laugh, as I have just discovered my own secret to rapid weight loss, namely methylprednisolone. Maybe I should run out and patent the “CLL Miracle Diet” before some doctor -- like Tom Kipps or Januario Castro -- gets inspired by the example of Dr. Robert Atkins and decides to it.

One side effect of taking steroids can be weight loss, especially if you are a bulky CLL patient like me. My experience, dropping 20 pounds in nine days -- about 10% of my body weight -- is consistent with what has happened to some other patients I know about.

As you will recall, I began taking 72 mg of methylprednisolone (MP) daily starting March 14 for a sudden case of autoimmune hemolytic anemia (AIHA). High doses of steroids (1 mg/kg prednisone up to 2X daily) are the standard frontline treatment for AIHA -- and in my case they are working. (For those of you keeping score: My hemoglobin was up to 11.3 as of yesterday, as opposed to its nadir of 8.9 on March 14, and I am almost starting to feel normal, or as normal as I get. Hematocrit went from a low of 26.9 on March 12 to 34.8 yesterday. Haptoglobin levels, which had been as low as 10, were up into the 70s after only two days on the steroids, 34–200 being the standard range.) I expect my red counts to be normalized very soon, and one of these days I will report on my theory as to why I developed AIHA in the first place.

The AIHA reared its ugly head -- I am reminded of the old Monty Python sketch "Nobody expects the Spanish Inquisition” -- just as I was undertaking low-dose Rituxan three times a week for 12 weeks as part of a plan to deal with CLL. My hem/onc and I had planned to add some low-dose MP toward the middle of that process to squeeze CLL out of the nodes and spleen, after first getting the peripheral blood counts down. This was the plan anyway, and it was completely upended by the AIHA diagnosis. In the immortal words of my doctor, who came rushing into the infusion room with scripts in hand, “How would you like to start the steroid part early?”

This turn of events has interesting consequences for the CLL as well as the AIHA. Readers of this blog know that I have long been interested in the concept of Rituxan + HDMP (high dose methylprednisolone), the protocol that has been used successfully in chemo-naïve patients at UC San Diego (and thus the source of my reference to Drs. Kipps and Castro in the first paragraph). CLLers following this protocol also know there is debate in the medical and patient community about its advisability, with some people swearing by it and others swearing you have to be crazy to do it. My own experience with MP at much lower doses, as well as with Rituxan in combination, is giving me some interesting insights into the issue. I promise to go into them in detail.

In the interim, suffice it to say that my AIHA treatment plan has had big consequences for my CLL, which brings us back to the weight loss. As you debulk, the weight has to go somewhere. Fortunately, methylprednisolone has lympholytic activity -- that is, it kills off CLL cells -- which are passed as urine. But it is by no means a miracle worker in this department. There are three compartments where CLL hides: the lymphatic system (including spleen), the bone marrow, and the peripheral blood. Steroids push the CLL out of the first two; what isn’t killed circulates in the peripheral blood, driving the absolute lymphocyte count upwards. If you let the CLL just float there, once you have stopped the steroids it is only a matter of time -- a couple of weeks, a month -- before the white trash is back in the other compartments, making babies and cleaning up after the hurricane.

This is why my hem/onc and I will meet Monday to go over the situation; my MP dosage was cut by 50% two days ago and I will probably be off of it entirely soon. Perhaps we will consider upping the Rituxan dosages to take advantage of this window of opportunity.

Not all of the weight loss is CLL. Muscle wasting is one side effect of steroids and it appears to be part of the problem in my case. (Muscles can be built back up, so it isn’t permanent.) This is why I ended up at a General Nutrition Center store yesterday, buying one of those clown-sized jars of “the world’s most powerful weight gain formula.” High protein, low glucose, a thousand calories in every 16 delectable ounces.

Indeed, the challenge for the past week has been to eat enough calories. Like almost everyone reading this, most of my life has been spent with the opposite problem. Suddenly I find myself in a bizarro world where ingesting exessive calories is a good thing. The other day, for the first time in my life, I ate steak and eggs for breakfast, swimming in butter. It is a sad day when you troll the nutritional information sheet for Burger King looking for the highest-calorie sandwich you can find (Triple Whopper with Cheese, 1230 calories). For once I am free -- nay required -- to eat with abandon, but I have to avoid things with lots of sugar, as steroids can raise glucose levels. I have a glucose meter at home and while my levels have gotten a little high at times, they have stayed well away from the magic number of 200, which is when we radio Houston and tell them we have a problem.

So I am eating more and enjoying it less. On the plus side, I haven’t looked this trim in about 20 years. There is an opportunity here, post-steroid, to build back muscle and stay at a lower, healthier weight. And, of course, there is an opportunity here to deal with the CLL in a more meaningful way than I have in the past, since I debulked much better than I would have imagined.

In the meantime, I have a spring in my step -- both from my returning red counts and my lighter weight. Thanks to all of you who have written me with your messages of support, as well as with some invaluable advice about managing life with steroids. The one thing I keep saying about chronic lymphocytic leukemia is that we are all in this journey together, and that our caring for one another makes an incalculable difference. I have learned first-hand recently that this is true.

Now I think I'll go have lunch. Bucket of chicken, anyone?

It's raining WHAT?

There’s a road in California pasture country called Brown Material Road. It’s one of my favorite road names, and there’s little doubt about the nature of the brown material that the name refers to. Well, Marilyn and I have been driving down our own Brown Material Road lately. Upping the metaphorical ante, let’s just say we’ve been caught in a shitstorm of events, the sort of telescoping of crap in a short frame of time that can tax your ability to cope on every level. A friend of mine was kind enough to provide a weather map showing a shitstorm over our home in Arizona, and it is posted below for your amusement, and mine in retrospect. (Hopefully it will not head your way as it meanders toward its usual resting place, Washington, D.C.)

Suffice it to say that one element of the storm is called Autoimmune Hemolytic Anemia, which I suspected I had on a Friday and which I began treatment for on the following Wednesday. So far, the treatment (steroids at a rather high dose, backed by cautionary antibacterial and antifungal drugs) seems to be working. This all sounds so easy as I write it, now that I have had a chance to catch my breath (oh God, an anemia pun of all things)! I promise to go into the experience in detail one of these days, as there is a lot to tell (not the least of which is the way this all is playing into my current CLL treatment plan, which was about to get started when the AIHA hit.)

But the part of the story I want to mention today is the importance of a patient being proactive. Thanks to all the time I have wasted reading CLL patient sites and groups on the internet, I was way ahead of everyone in suspecting what was really going on, in insisting on the appropriate tests, and in getting the attention of those in the busy hem/onc’s office who needed to know and to act on my behalf. Now, sometimes I make lousy decisions, but in this case Marilyn and I played it just about right: the lesson is, if you want to get good medical attention, do whatever you have to to get the ball rolling and then monitor the process closely, making sure the ball gets to where it has to go. This made the difference between me getting help in time and me collapsing on the street and needing transfusions.

And so a word of thanks is in order. This was the first medical crisis, as it were, that I have had with my CLL. Being able to quickly access information from CLL Topics (thank you, Chaya and PC), the Professors’ Posts on ACOR (thank you, Susan and Terry), and the experiences of fellow patients on CLL Forum (thanks, Denise and all) helped save my butt. I did not have to reinvent the wheel and was able to come up to speed on the subject quickly. What a marvelous (worldwide) web we weave when first we practice to CLL deceive.

So I am now recuperating and looking at the effect of this on my CLL treatment plan -- 72 mg of methylprednisolone daily does wonders for slimming the neck and spleen and pushing crap out of the marrow, if only it could be made sort of semi-permanent in a non-toxic kind of a way . . . And, of course, there is dealing with the other non-CLL issues that have hit us like frozen blue ice falling from an airplane toilet in the sky. So while this plays out I may be rather absent from my usual internet haunts, and I may not post here quite so frequently. Other priorities demand my attention. When the shitstorm hits, you drop everything but the most immediate and essential. But I’ll be back with my story one of these days, and I expect to have some interesting things to tell. Meanwhile, watch out for brown clouds on the horizon.

Truncheons and dragons: 13 ways to fight CLL

“How long do I have, doc?” It’s a line from the movies that people with chronic lymphocytic leukemia sometimes repeat after they’ve been diagnosed, which is when life can start to seem like a B-grade B-cell melodrama.

It’s a natural question, and one that is unanswerable. CLL varies greatly in its aggressiveness and in patient response to treatment. I read the statistic somewhere that about half of all CLL patients will die of the disease, and we now know that certain prognostic test results can indicate which patients may be more likely to have disease that will progress. But that doesn’t mean they’ll die; even patients with the worst prognostics can get lucky and have a stem cell transplant that cures their CLL. Ultimately, “how long you have” is still the province of Fate rather than man.

So, to the oft-asked question “How long do I have to live?,” I offer in reply a paraphrase of John F. Kennedy: “Ask not how long you have to live. Ask what you can do to help yourself live longer.”

In that spirit, here are some suggestions that may help keep the dragon, as some people are wont to call leukemia, in its place:

1. Get yourself a good local doctor. Qualities to look for: thoroughness, thoughtfulness, a willingness to listen and learn, to read stuff you bring in off the internet, to explain things clearly, to work with a CLL expert. Qualities to avoid: rigidity and dismissiveness. In his book Come Hell on High Water (A Really Sullen Memoir), Gregory Jaynes writes about a fellow passenger on a ship: “It occurred to me that he has the self-confident bearing of a successful and God-like physician, either that or an extraordinarily secure idiot; for most of my life I’ve been incapable of telling the two apart.” Doctors aren’t infallible, and a good one -- no matter how accomplished or famous -- brings to his work a healthy dash of humility. CLL is tricky and the landscape of care is in an almost constant state of change, so it should humble everyone who toils with it.

2. Consult at least one CLL expert, preferably two at different institutions. Experts often disagree and their views may be colored by the research their own cancer center is doing and the clinical trials they are conducting. (When visiting a CLL expert, avoid getting caught up in the moment and agreeing to jump into a clinical trial without giving it some thought and research.) All this makes the good local doctor all the more important: It helps to have an honest broker who can, with impartiality and from the vantage point of distance, help you sift through both expert recommendations and the latest ideas for treating the disease.

3. Go with a friend. I hope you have a spouse or a relative or a friend who is willing to hold your hand, lend a shoulder to cry on, go to the doctor with you, help you take notes, ask questions, and sort through what CLL means on all levels. Caretakers provide emotional support as well as a second brain when dealing with complex medical issues. Remember to give them your love and gratitude, as well as this important gift: time and space of their own, away from CLL. (And if there is no one close at hand, patient websites such as CLL Forum have a number of members who are willing to help from a distance; for face-to-face contact, the Leukemia and Lymphoma Society provides local support meetings.)

4. Do everything you can to find or maintain the best health insurance possible. What good is the best treatment or most important test if your insurance won’t pay for it? Finagling good insurance is worthwhile, even if it means a career change or moving to another locale. (Readers of this blog know that my current insurance won’t pay for stem cell transplants and that I have to do something about that. Stay tuned.) A very useful website covering insurance laws and options in all 50 states is this: http://www.healthinsuranceinfo.net

5. Have your prognostic tests done so you have some idea of what you’re dealing with. These tests are IgVH mutational status, FISH, and CD 38. Making a treatment decision without knowing these is foolhardy. There is a growing body of evidence that these tests can indicate which patients are more likely to have progressing, even aggressive, disease; this evidence also shows that there are different responses to treatment depending upon these test results. The risk-based approach to CLL is the wave of the future and the future is here now. Quest Diagnostics is covered by most US insurance plans and can run all three of these tests; you usually can have the IgVH test done for free as part of a visit to a CLL Research Consortium center. Dr. Terry Hamblin’s lab in the UK can also do the tests. (ZAP-70 is a valuable test but it is in the working-out-the-testing-kinks stages; it is best done at a research institution such as UC San Diego as opposed to a commercial lab such as Quest.)

6. Become familiar with the criteria for starting treatment, especially the NCI guidelines, and remember that good doctors believe one should “treat the patient, not the numbers.” Take a look at Dr. Hamblin’s three-part blog post titled What is the aim of treatment? Learn to finesse the treatment choices in front of you, to judge their potential risks and rewards, to consider how they can be timed and staggered for your greatest benefit. Consider the opportunity cost in waiting too long or starting too soon. These skills are something that come with knowledge and experience, yet they are essential to charting the right course. Even then, there are no sure answers, just educated guesses (and making the occasional mistake can be part of the struggle). If you are in "watch and wait," use it as a time to learn.

7. Take the long view. Ask what treatment you’ll do when you relapse from this one. Make a flow chart if you have to. Strategize for the future. CLL is like baseball -- it has nine innings, not one, and it can even go into overtime. You can win the first inning -- and in CLL treatment, you almost always do -- but that won’t help in the long run if you lose the ones that follow.

8. Use the internet. Run your questions and ideas by your fellow patients in discussion groups such as CLL Forum and the ACOR list, read sites such as CLL Topics and Dr. Hamblin’s blog. Between these four sources alone there is enough information to answer all your questions, bring you up to speed on the latest in CLL care and management, and offer a valuable perspective on the choices in front of you. All you have to do is read and participate. Is your life work a little homework, a little networking on the net? Whatever you do, don’t keep your own counsel. It is said that a lawyer who represents himself has a fool for a client. The same can be said of a CLL patient who reaches conclusions and doesn’t run them by others, including doctors and fellow patients. No matter how smart or clever you think you are, CLL is a tricky business and you will benefit from sharing your suppositions with others.

9. Avoid comorbidities. Take care of yourself -- adding lung cancer or heart disease or diabetes to the CLL equation only complicates matters and narrows your choices. In other words, quite the freaking cigarettes and don’t embrace your inner glutton. The more fit you are, the better you will respond to therapy and the greater your chances of a successful transplant, if it comes to that.

10. Be proactive. If you get a strange symptom, take it seriously. If your doctor’s office is slow to respond to something, or if a nurse appears to be confused about things, or if your health insurer balks about paying for a needed test, set them straight. You can often catch more flies with honey, but be a pain in the ass when you have to. I saw a T shirt once that read: “The more I complain, the longer God lets me live.” There is a certain truth to that.

11. Don’t get freaked out by your "new normal" to the point that you make decisions based on fear or panic. Do things such as yoga, exercise, and meditation to maintain a calm, centered focus and to keep CLL in its place as only one part of your life, not the whole of it. As one patient recently put it, "Every morning I look outside to see our beautiful world. Great weather, terrible weather, it doesn't matter. I step outside and draw in a huge breath and thank God for letting me have another day here on earth. That takes the edge off anything that might cause grief the rest of the day. It's already started out as a good day." If and when the monsters start lurking in the night, remember my favorite panic button quote, from lung cancer survivor Greg Anderson in the book 50 Essential Things to Do When Your Doctor Says It's Cancer: “Panic is a projection that is not real. We are not just our fears. Our fears do not necessarily determine our future. This is significant.”

12. Don’t give up. Where there’s hope, there’s life. If you doubt what I’m saying, read Dr. Jerome Groopman’s The Anatomy of Hope. People beat the odds daily. You can, too.

13. In the final analysis, always trust your own intuition, and make no important decision without consulting it. If something doesn’t feel right, don’t do it. When you find a course of action you truly believe in, put your soul, as well as your body, into it.

"Watch and wait"

Hanging on

Some friends of mine were wondering: Is a transplant worth it in chronic lymphocytic leukemia? Is it worth the potential hell of graft v. host disease? Is it worth the risk of failure or relapse? Is it not better on some level to get a great remission (or two) with chemotherapy and live to the fullest in the time before the disease claims you piece by piece? At some point, might it not be wiser to take a shortcut -- perhaps assisted suicide? -- around all the pain and trouble, complications and disappointments, that come with progressing disease, shutting doors, and a body at war with itself? There is no cure, and we know the suffering that the long drawn-out end might bring, so why endure it, and why visit it upon our loved ones?

That's tough stuff to hear. But these sorts of questions can weigh on the minds of CLL patients with progressing disease, especially younger ones for whom the bell seems to toll all too soon. We are the rock and roll generation, after all: Live fast, die young.

CLL affords its victims the grace of time -- time to say goodbye, to make amends, and to think about the consequences of fighting, and of not fighting. Those who had always hoped for a quick and painless passing may find this discomfiting. With CLL, one's passing might be relatively painless, but it is not quick.

And so it is legitimate to wonder about things that our friends and family would rather not hear. Some of you reading this are no doubt thinking "I wish Dave would write some more about his automated trash can." But death is potentially part of the CLL picture, and it is a fair topic of conversation.

And so I entered the discussion my friends were having, and this is what I said (with a little extra added in hindsight, as is a writer's prerogative, thus making me seem much more erudite than I did at the time):

There is a time to lay down one's arms, give up the fight, and go gently into that good night. This is when people quietly decide enough is enough and simply give themselves permission to let go, letting the end come when and how it may. Some go into hospice, some stay at home; I’d like to drag myself to the beach and stare at the sea and be carried away by its rhythm.

But for me, that time will not come until every avenue is exhausted. I have heard transplant stories, and transplants can be a living hell, but they can also be relatively easy. Even for people who have to put up with all kinds of problems, the benefits can outweigh the drawbacks. Patient blogs tell the story: A 17p-deleted patient on her second transplant who, despite skin problems, goes on a cruise. A young father, in his 40s, who suffers post-transplant seizures but finds them a small price to pay for the privilege of being here with his wife and kids.

So long as I can prop my ass up in bed, hold the hand of the woman I love, laugh at stupid puns, listen to music, see the hawks flying outside my window, taste a fresh apple, and smell the desert sage after a rain, I will fight this thing.

Why not do a transplant now, cut out all the intervening waiting and worrying and fighting that can drain you emotionally, financially, physically? Well, transplants are risky (even if they hold out the promise of a cure for some) and the longer I wait, the better the procedure will get. It's all a matter of timing. I'm 50. I can wait 10 years, if the disease will allow it, which it probably won't. But I can have a pretty good quality of life for the next however many years, and then roll the dice.

I am not a gambler but this disease is making me one. CLL is all about gambling. Dice. Poker. (Russian) Roulette. Pick your metaphor. Leukemia is filled with games of chance. Timing is everything, along with luck.

Sure, it's tempting to go with something like RFC to get a great remission now and not have to worry for awhile. But the cruelest thing about this disease is that these remissions don't last, and they get harder to duplicate. Is chemo a fool's paradise? Or does it allow for a last bit of real paradise (aka disease-free living) before the shit truly hits the fan? I can't fault anyone for going with chemo now; who knows how it will all turn out. The best we can do is play it as we see it.

Should we avoid a transplant, sit tight for as long as we can, and wait for a cure? (Calling Mr. Godot!) I don't think we'll see a cure anytime soon, especially for those of us who have gone beyond the infancy of the disease. Honestly, I think we're at least 20 years away from a cure. A CLL expert doctor once said that the fight against CLL will be one long war of attrition. I think he's right. What this means is that we patients have to play the game with the cards we're dealt today. (Who knows, maybe we can exchange a card or two if things go right; I don’t think a cure will come soon, but I do believe there will be incremental progress in treatment.) None of this is a reason not to stay in the game.

And so I say, hang on.

There will be plenty of time to explore the world after this one. So long as the sun rises and there is music to be made, so long as there are exotic ports of call and children to hug, this life grants enough small pleasures to make the pain of struggle worthwhile.

So, hang on. As long as Marilyn can hold my hand and I can know she's there, I'm going to hang on.

Today is our 24th anniversary. I do not know if there will be twenty-four more. But it won’t be for lack of trying. Happy anniversary, my sweet. Together, we will see what love can conquer.