Thursday, December 29, 2005

Just what the doctor ordered

Dr. Michael Keating of MD Anderson is famous for writing out “prescriptions” for bottles of champagne for new CLL patients. There is a certain poetry in that message -- the joy of life does not end with diagnosis -- and I think the prescription is appropriate so long as patients follow their bubbly with a healthy dose of patient education.

For, alas, man and woman cannot live by champagne alone. But around this time of year they can sure as hell try.

After we graduated from the University of California at Santa Cruz, Marilyn and I took a trip to Europe in the summer of 1980. We fell in love with France, and found the French to be, by and large, friendly and accommodating. Traveling on a frayed shoestring of a budget, we stayed at such places as the Grand Hotel de La Loire in Paris, which was anything but grand –- the hotel, I mean. Paris was wonderful –- romantic, beautiful, exemplary in every way but for the dog poop that littered the streets -- and our eyes still tear up at the thought of an artichoke in hollandaise sauce that we had at a cafĂ© on the Ile St. Louis.

Being on a budget, we sometimes opted for an in-room dinner of cheese and wine. We discovered that cheap cheese is a good bet in France but that cheap wine is not. We did find bottles for $1, which may as well have been labeled “Apellation Merde Controlee.” A side trip to Rheims, in the heart of champagne country, confirmed that cheap champagne is not especially drinkable, either.

Alas, we could not afford the really good stuff, and a trip back to Champagne, with a jaunt over to Burgundy, is definitely in our plans (CLL and airborne infections be damned; to get to France I’ll wear a Darth Vader mask on the plane if I have to. When I deplane you can stick a straw in it, point me toward Mumm, and I'm good to go.)

In the meantime, we have enjoyed some excellent French champagne from afar, as well as California bubbly, including our favorite budget bottle, Korbel’s Blanc de Noirs. It’s available this time of year for under $10 a pop, and this is when I run out and buy a case to keep for special occasions for the year.

Those occasions occur whenever Marilyn and I decide there is need for one. There are worse vices, and, no, I don’t know if champagne has any synergy with Rituxan. But the placebo effect is well worth investigating.

Happy New Year!

Tuesday, December 20, 2005


This is the season of the winter solstice, the birth of Jesus, the Jewish festival of lights, and the remembrance of Kawanzaa. Across many cultures, it is a time of coming together, of the celebration of community through acts of faith.

Sometimes I feel like I have been on the outside looking in, kind of like a kid with his nose pressed to the glass, peering into a toy store filled with mysterious and shiny and curious things. Let me explain.

My parents came from very different religious backgrounds. My father is Jewish, but Jewish more as a culture than as a religion. His parents emigrated from Russia while the tsar still sat on the throne, in part because their heritage made them targets of discrimination. My grandmother, for example, survived a pogrom against the Jews and recalled being pulled into a doorway to hide from Cossacks thundering by on horseback. In America, my grandparents settled comfortably into a Jewish neighborhood in New York City. Their desire was not really to practice faith as much as it was to simply live in peace and raise a family in a land where they had as much opportunity as anyone else. My father got a limited religious education, and is not especially religious himself.

My mother was farm-raised in Oregon, daughter of two devout Christians; each of her parents were so devoted to their own church that they went to separate churches, and she went with each on alternating Sundays. One week she was Episcopalian, another week Lutheran. By the time I knew her she was vaguely Christian in a mainstream way, and had somehow picked up a mistrust of Catholics, Mormons, and what she called “Holy Rollers,” meaning Baptists and television preachers of all stripes. She seldom attended church (perhaps out of confusion as to which one to go to) but felt it would be a good thing if I attended church.

I should point out here that my parents separated when I was four and divorced not long after. As part of the custody agreement, I was to spend summers in New York with my father and the school year in Arizona with my mother. It was a cross-cultural bonanza from which I am still recovering: In New York, I wandered the halls of the Museum of Natural History, ate matzah ball soup, and took in the rides at Coney Island. In Arizona, I lived on a remote Indian reservation where my mother taught elementary school. The school, and the teachers’ apartments, were built across the road from the ruins of an internment camp where Japanese-Americans were forcibly confined during World War II. Not far away were the railroad tracks, where real-life hobos made camp, and when I went out to play my mother was forever telling me to avoid both the hobos and the rattlesnakes. Scorpions were a given.

The wonder, and wonder, and wonder years

In the midst of this, when I was about five or six, my mother decided that we needed to attend church. And so we did, consistently every Sunday, so much so that I was awarded a picture of Jesus that glowed in the dark, which I thought was the coolest thing in my room. It was in church that, my mother imagined, I would receive the tools to become a decent human being, to avoid impulses that might turn me into a hobo, or a resident of Manhattan. Perhaps she also hoped to stick it to my father, for she once let me send him a card that said “Happy Easter.” Who knows.

At any rate, what she did not count on was my natural curiosity, put into overdrive by what is probably the greatest lesson she ever taught me, imparted when I was taking fairy tale stories a bit too literally: “Don’t believe everything you read!”

The result was that I simply could not wrap my mind around what I was hearing in church, and the Biblical stories of miracles did not meet my literal standards of evidence. I did not see how Moses could have parted the Red Sea, for example. I had tried to part water and it simply wouldn’t work. And if Rumplestiltskin’s maiden couldn’t really spin straw into gold, how could Jesus have turned water into wine?

Jesus was presented to us in Sunday school as something of a benevolent Big Brother, always watching you. When I was given a post card of Jesus, standing about thirty stories tall and looking into an office building, I was incredulous. Nobody was thirty stories tall, and if Jesus were that big, he would be crushing cars in the street, which would be very un-Jesuslike. I also did not see how Jesus could be looking everywhere at once, for I already had the sense that there were a lot of people and a lot of places on Earth.

My babysitter was an Indian lady named Barbara Claw. She was religious, and insisted that what the preacher said was true, that Jesus could see you everywhere. So I hid in her clothes closet and asked if Jesus could see me there, and when she said "yes" I found another hiding spot and repeated the question, and this process went on and on until Mrs. Claw had to be wondering if the good Lord was testing her patience.

Beyond this search for literal truth, some other things also bothered me. If God was all-powerful and loved humankind, how could he allow there to be a Hell? Why would God favor one group of his children over another?

Eventually, when I got to be about seven or so, my mother discontinued church.

And so it was that I remained free of religious training, left on my own to figure out the mysteries of life. Ultimately I did absorb some lessons from the Bible, for despite all my questions, certain things made a great deal of sense: The Ten Commandments, for one, and also the Golden Rule, which sums up in one sentence how best to live one’s life: Do unto others as you would have others do unto you.

As a teenager I began to wonder about matters of faith rather seriously, and I was able to see that there is wisdom at the heart of many religions, however much the trappings may ring false. I also began to learn more about history, and became dismayed at religious intolerance, the monstrous crimes committed in the name of God. All this led me, briefly, to the Baha’i Faith, which preaches a message of tolerance and the unity of all religions. But as much as I appreciated some of the principles of the faith, I could never quite get myself to believe in the details, which is, as we know, where the devil resides.

Faith without religion

And so I have been going through life ever since, living in a society where many people are comfortable believing things that I cannot. This does not make them wrong and me right, and this does not mean that I am not a man of some faith.

On the contrary, I am.

CLL, which brings with it a powerful reminder of mortality, no doubt tests, or challenges, the faith of all who acquire it. You would think that I, without a church or temple to retreat to, might find this particularly hard. But over the years I have learned to believe in the beauty and goodness of life, of which uncertainty is a part, and this is good practice for the calamity of cancer. I have developed a faith through experience, brick by brick, that is, I have discovered, pretty much unshakeable. If the edifice is not ornate, it is nonetheless solid.

It is hard to define this faith, except to say that I hold as a central tenet that life is a gift, be it purposeful or accidental, and that the energy expended to live it is more profitably spent on doing good than on doing bad.

I believe we never left the Garden of Eden, that it is all around us, that man never fell but has yet to rise to his full potential. (I use "man" in the collective sense of traditional English, for I believe that women are every bit the equals of men.)

I feel that I would be a fool if I claimed to know how the universe began. I know what science says, but science is incomplete, and I still have the same question that I had when I began to take science classes as a kid and started asking difficult questions: What was there before the Big Bang?

Science cannot answer that question, and “nothing” has never made sense to me.

Closer to home, here on Earth, I can see that evolution works. I accept the DNA evidence that shows that we are, indeed, cousins of chimpanzees. I see consciousness and emotion in a variety of creatures, and believe these things are not reserved for humans alone. I believe this awareness, all we are, could simply be a result of the complexities of our brains, our neurons, our cells. I also believe that it could be something other than that, for as Hamlet said: “There are more things in heaven and Earth, Horatio, than are dreamt of in your philosophy.”

Whatever the source of our consciousness, I believe that it may or may not end at death. I have read enough compelling accounts of near-death experiences and reincarnation that I cannot dismiss these possibilities. I watch as science tends increasingly toward esoterica such as string theory, and this all reminds me that if there is one thing we know it is this: We do not know.

And so my faith takes that as a central tenet, too. It accepts that there is much we cannot know, and focuses instead on what we can do: Right what is wrong, mend what is broken, take what is given, give more to take.

And so, in that sense, I am not left out in the cold this time of year, after all. I can share with my brothers and sisters of all faiths and no faith at all what we have in common that uplifts us. And so to you, whatever you believe or don’t believe: May the universal message of peace and tolerance, love and forgiveness, and joy and hope ring through the clouds, echo off the mountains, and find its way to the homes of you and yours.

Below is a photo of a rainbow taken from our home in Arizona. Rainbows we can all see and believe, even if we do not know what lies at their end. One day, perhaps, we will find out.


For a short but sweet overview of agnosticism, Wikipedia has a fine article at:

I guess I would be an "agnostic spiritualist," according to the article.

Thursday, December 15, 2005

EGCG, without apologies

There is a bit of a tempest in a teapot going on over at ACOR, so I thought I might comment here at some length about EGCG, the green tea extract that has created a buzz in the CLL community for the past couple of years. (Alas, the buzz is not always pleasantly psychotropic.)

This all started when researchers at the Mayo Clinic found that EGCG could kill CLL cells in vitro, which means in a test tube. They thought the results were encouraging enough to justify conducting a clinical trial to test its effects in vivo, which means in people. In this they received the support of CLL Topics, the nonprofit educational and patient-advocacy organization, which contributed patient donations to help get the trial started. Chaya Venkat of Topics wrote some articles explaining the science of how EGCG is thought to work against CLL, and Topics has taken a generally positive outlook on the subject.

Patients, looking for something to do at home to combat CLL, began taking EGCG in its myriad forms: drinking green tea, ingesting capsules and tablets, sucking on EGCG-laden candies. Everything but snorting lines of it.

These clinical trials of one have reported different anecdotal results in the online patient forums: some people say it has knocked their lymphocyte count down, some say it has helped steady it, some say it has done little or nothing. As a rule, the anecdotal reports that do claim progress show results that have been incremental, not earthshattering. Dosages have been all over the map since no one knows what the optimal dosage is.

The trial now underway at Mayo, which is co-sponsored by CLL Topics and the National Cancer Institute, is designed to determine that. The trial is a Phase I/Phase II study with an expected total enrollment of 69 patients. These things tend to take time, and we will probably not know the results for another year or so.

In the meantime, Mayo researchers have just issued a brief report in Leukemia Research that, while unrelated to the trial in progress, provides some encouraging, albeit anecdotal, information. Here it is, written in Mayo-ese:

Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies.

Shanafelt TD, Lee YK, Call TG, Nowakowski GS, Dingli D, Zent CS, Kay NE.Mayo Clinic College of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Green tea or its constituents have long been touted as a health promoting substance including claims it may have cancer prevention properties. We previously reported the in vitro ability of one tea polyphenol, epigallocatechin gallate (EGCG), to induce apoptotic cell death in the leukemic B-cells from a majority of patients with chronic lymphocytic leukemia (CLL). After the publication of our findings many patients with CLL and other low grade lymphomas began using over-the-counter products containing tea polyphenols despite the absence of evidence to suggest clinical benefit, definition of possible toxicities, or information on optimal dose and schedule. We have become aware of four patients with low grade B-cell malignancies seen in our clinical practice at Mayo Clinic who began, on their own initiative, oral ingestion of EGCG containing products and subsequently appeared to have an objective clinical response. Three of these four patients met criteria for partial response (PR) by standard response criteria. Although spontaneous remission/regression is occasionally observed in individuals with low grade B-cell malignancies, such events are rare. Several patients presented here had documented steady clinical, laboratory, and/or radiographic evidence of progression immediately prior to initiation of over-the-counter green tea products and then developed objective responses shortly after self-initiating this therapy. Such anecdotes highlight the need for clinical trials of tea polyphenols to define the optimal dosing, schedule, toxicities, and clinical efficacy before widespread use can be recommended. An NCI sponsored phase I/II trial of de-caffeinated green tea extracts for patients with asymptomatic, early stage CLL opened at Mayo Clinic in August 2005.

What does this tell us? That some people at Mayo think there may be something to all this, but that we need to wait for clinical trial results to know for sure.

This most recent abstract has led to a bit of a kerfluffle among patients, a few of whom see it as questionable science offering hope where little is justified. While I disagree with them, they are right in that we should hold researchers to the highest standards of evidence, to the proper controls and precautions that Dr. Terry Hamblin has spoken about in several venues, including ACOR and CLL Topics.

But this one abstract reports news that is clearly described as anecdotal; the researchers claim nothing more than that, and they use their observations to reinforce the need for the trial. Mayo is a reputable, straight-arrow institution and will in time issue a full report on its trial. And Mayo is not known for constructing Potemkin villages when it comes to scientific information. I would expect the trial to be competently conducted and the results to be completely reported. When those results are published, we can parse them, and the trial, all we like.

In the meantime, there appears to be little harm in drinking green tea or taking EGCG capsules or candies (though I have to wonder about the green tea potato chips pictured on the right). It won't cost you much, and it will turn out to be money well spent if Mayo comes up with something. If they don't, little is lost (except perhaps for some weight, since green tea seems to have that effect in some people).

My guess -- and this is only a guess, but I'll wager a pot of Japanese gyokuro on it -- is that the results will show some positive effects in some early stage patients (and perhaps little effect in some others).

Whatever the results, EGCG will not prove to be the long-awaited cure. It may, however, join the arsenal of weapons we use to get at CLL cells, one made especially attractive by its ease of use, availability, and extremely low toxicity.

Sometimes I think that, in our hope for progress against CLL, we expect too much of a drug, and we become upset when the results do not match our expectations. I certainly understand this frustration, as all sorts of "promising" things have come down the pike over the years, only to disappoint us. But something that might lead to a partial response in some patients -- especially a low-toxicity something -- can still be of great benefit, even if it is not exactly the cure we hope for.

Dr. Hamblin once said that the war against CLL is a war of attrition, that it will be won incrementally. By this, I think, he is also telling us that it is unlikely that there will be a magic bullet anytime soon. From what I can see of the CLL landscape, I agree with him.

So, my advice is: Keep your expectations reasonable.

And as to the Mayo trial: Watch and wait.


The Mayo EGCG trial, explained in easy-to-understand terms from the Mayo website:

The Mayo EGCG trial, explained in greater detail, from the NCI:

Everything you've always wanted to know about the Mayo EGCG trial, including an interview with the researchers, reported in CLL Topics here.


Here it is, almost two years after I wrote this post, and we have an inkling of some news from Mayo. According to Chaya Venkat, who wrote to me today, "The phase I of the trial is completed, and new recruitment is suspended until the results of the phase 1 are reported and they reopen for the phase 2 stage of the trial. To the best of my knowledge, the results of the phase 1 have been quite encouraging."

Anecdotally, from reports in various patient forums, things are about the same as when I wrote the original post. A few patients seem to have responded really well, some may have gotten a small benefit, some have found no effect, and there have been rare reports of a suspicious rise in lymphocyte count after taking it. A few people have also reported that it has appeared to lower their platelet count, and I recall reading somewhere that it can act as a blood thinner. The platelet issue is one reason I stopped taking it. I have had the stuff in many incarnations and in large doses and it seems to do little for me one way or the other. But I see no harm in anyone trying it; you might be one of the lucky ones. An interesting anecdotal observation by someone I respect is that it appears to work better on those who have not been treated than on those who have, and this would include Rituxan. Like everyone, I anxiously await Mayo's report on Phase 1. -- November 20, 2007

Wednesday, December 07, 2005

The three-day rule

Perhaps you’ve heard of timeshare resorts. Maybe you’ve been pestered by mail, or by phone, to join one. If you plunk down a lot of money -– say $20,000 -– you’ll “buy” a few weeks of vacation a year at a resort, which you can then trade for a stay at another resort affiliated with the timeshare company.

Innocent citizens, lured by the promise of a free weekend or a complimentary off-brand television, have been known to voluntarily subject themselves to what is called a timeshare presentation. This lasts two or three hours and is, to my way of thinking, the second or third circle of hell. It involves a tour and a video, usually featuring a has-been TV star extolling the virtues of the timeshare dream while standing on a sandy beach. The worst part is the conclusion, sitting with a high-pressure salesman (or “closer”), whose job it is to get you to sign on the dotted line before you leave that day. The salesman will be very friendly, and you will be plied with free hors d’oeuvres.

While most people just take the television and run, there are those who get swept up in the moment, who see themselves skiing in Tahoe and snorkeling in Hawaii and clinking wine glasses in Paris. They get out their checkbooks and sign on the dotted line. Then a small bottle of champagne is
uncorked, the sound of which is a signal for all the salespeople in the room to applaud. Those who make the "right" decision are thus rewarded with the approval of the tribe.

Fortunately, laws have been passed to protect those who wake up the next morning, as if with a bad hangover, and say "What the hell was I thinking of?" If, within three days, you change your mind, the law lets you out of the deal with no penalty.

That, my friends, is the three-day rule. Now, let’s see how it applies to CLL.

Speaking of money, I will now save you $30,000

Let’s say you are at the thinking-about-treatment stage. You go to see a doctor -- could be the local oncologist you’ve been working with for years, could be a big name at one of them fancy CLL Consortium places.

You visit with the doctor, and the doctor says; “OK, you can get a nice remission with Treatment X.” or “You’re in luck, Here’s this new clinical trial we’re running and I can get you in.” Or some such. And the process can be started that very day, the scheduling, the insurance paper-filing, and so on. Hey, they might even get you in the chair tomorrow! Problem solved.

Or is it?

If we have learned anything about CLL, it is that individual cases must be finessed with the greatest of care. It is not just me saying this. Here is a quote from Dr. Michael Hallek, whose excellent paper CLL: First-Line Treatment is one of the highlights of this year’s ASH conference:

“With the potential of potent chemoimmunotherapy regimens, choosing the right treatment for a patient with CLL has become a task that requires skill and experience.”

And what is maddening about CLL is that even the experts can disagree. People of skill and experience may offer you different options, depending upon what research their institution is pursuing at the moment, or what clinical trials they need people for, or based upon honest differences of opinion.

For example, if you are a patient with a mixed prognosis heading toward treatment for the first time, I can guarantee a 90% probability that the following will happen if you visit the following Consortium institutions, which would run you at least $30,000 out of pocket if your insurance won’t pay. (I am not psychic; these observations are based on reports from fellow patients during the past year or so.)

MD Anderson will recommend something with “FCR” in the title.

Ohio State will suggest RF.

The Mayo Clinic will suggest PCR.

UC San Diego will recommend R + HDMP or an immunotherapy trial such as AT-101 or 17-AAG.

(Now, if I have just saved you some money, please don’t run out and buy a timeshare.)

Make like Elvis -- leave the building!

So here’s my advice, which runs counter to human nature, but which is probably one of the best pieces of advice I can ever give you (and again, I am not psychic -- this is based on the experiences of many patients, including myself): Politely thank the doctor, tell him or her that you want some time to think about it, and leave the office without scheduling or arranging for the suggested treatment. Even if the doctor is famous. Even if you really like the doctor.

Give yourself at least three days to learn more about the treatment: Google it, visit CLL Topics and do a site search for it, look in the ACOR archives for posts on it. E-mail your fellow patients, post to patient lists. Get a second opinion from another doctor. Examine the side effects, the track record, how the different drugs may affect people with your cytogenetics or other conditions that may complicate your case of CLL.

Then go for a walk in the woods, or on the beach, or do whatever it is you do to get in touch with your calm, centered, intuitive self. On all levels, scientific and medical, mental and emotional and spiritual, chew on the treatment. Does it feel right?

Then, and only then, should you decide what to do.

But I want it to be over!

I said this runs counter to human nature, and I know all the arguments. They are so very, very tempting. I have been tempted by some of these myself:

I have cancer. My counts are rising. My lymph nodes are popping up. This is an issue of such magnitude that I cannot afford to wait.

The doctor is an expert. I am an idiot compared to the doctor. If I don’t agree to his suggestions, he will think I am stupid.

I am a nice person and I don’t want the doctor to think I am a pain in the ass. He is a nice person and I want to please him.

I will lose the doctor’s trust by being uncooperative. He will throw me out of his office and I will be barred forever from his expertise. The security cameras in the lobby will be programmed to recognize my face and a red light will go on somewhere if I ever enter the building again.

The doctor says that this new treatment is working so well that it might even cure me, or come close. I know this disease is supposed to be incurable, so how can I pass up a chance like that?

I have taken time off from work and have flown/driven/ridden an uncooperative mule all this way to see the doctor. It is costing me a lot of money to stay at the Hyatt/Ramada Inn/Motel 6. I want to get my money’s worth from this trip. If I go away empty-handed, so to speak, I have wasted my time. I can’t keep doing this.

My friend/family member/local doctor/fellow CLL patient said this is the place to go. I do not want to disappoint them. Others have been happy with their treatment here. What makes me so “special” that I shouldn’t be?

If I am treated here, I am getting “the best.” People of my accomplishment/wealth/intelligence/incredible beauty deserve to get the best.

I just want it to be over. I’ve been watching and waiting and worrying for a long time. If I have to do one more search on the internet or deal with one more unexpected complication or confusing concept, I will scream.

The end game

There’s an old saying among dieters: “A moment on the lips, a lifetime on the hips.”

This applies to chemotherapy, too. It has consequences, for good or ill. It can help for a long time, or for a while, or it can make things worse, even blow your chances for responding to a better treatment.

Remember what Dr. Hallek said in that one sentence I quoted: Today's chemotherapy regimens are "potent." Their administration requires "skill and experience." This serves to remind us that there is the practice of medicine and there is the art of medicine, and that they may be two different things. Even a doctor with the biggest practice, and the biggest reputation, may not be artful; I believe that the wise patient is the one who walks away. The big secret with timeshares, despite the pressure to commit on the day of the presentation, is that you can always go back the next week or the next month and make the purchase. The same is true when it comes to treating your CLL.

But if matters of ego, or of ostrich-ism, are more important to you than your survival, then by all means make a snap decision, get swept away in the moment, uncork a bottle of champagne, and hope for the best. Maybe it will, indeed, work out.

Just remember that there is no three-day law to protect you, nothing to turn back the clock once a drug has entered your veins. I know cases of people who have regretted jumping the gun on treatment, who got swept along and wonder, after the fact, if they did the right thing. Perhaps, in fact, they did -- but it is not pleasant to have such doubts.

This is life and death, not buying a timeshare. There are no guarantees, of course, even after you have done all the right things, that the treatment you choose will ultimately be successful, or the best possible thing for you.

But the more you think about it, the harder you keep on trying, the better the odds.

The fight against CLL is all about bettering the odds.

Take the three days.



Michael Hallek’s article CLL: First-Line Treatment nicely sums up the state of CLL treatment today and where things are headed. This is well worth a read, whether you are considering treatment or not:

Saturday, December 03, 2005

An Orwellian illness

I have a new name for CLL: Orwell's Disease.

In George Orwell’s 1984, nothing was as it seemed to be. “Newspeak” was the language used by the authorities to control society, and good citizens were supposed to accept contradictions as if they made perfect sense.

Fortunately, society never reached the point that Orwell describes -- or hasn't yet -- but misleading language is everywhere about us. People with CLL hear terms like “good cancer” and “complete response” and “normal karyotype,” which seem to imply things that are, in fact, not the case. We are even told that CLL is "incurable," when in fact it is curable. In CLL, black is white and white is black with frightening regularity. Orwell could not have invented a more brilliantly contradictory disease if he had tried.

What makes this a serious problem is that these terms are often taken at face value, and they become part of the process by which we make treatment decisions. So getting clear on what they mean -– and don’t mean -– can be a matter of life and death.

"Good cancer"

“Good cancer” is my nominee for the Mother of All Oxymorons. Enduring this phrase is a rite of passage for most people with CLL. It is harmful on two levels: First, it can lead people who don’t have CLL to think that those of us who do have little to worry about. Second, it can convince us of that, too.

It is all too tempting, and too easy, to wander blithely along, reassuring oneself that CLL is no big deal. There are no doubt many of our brethren out there right now doing so, and some of them are in for a very rude surprise.

Only about one third of people with CLL die of causes unrelated to CLL, according to a current American Society of Hematology report by Guillaume Dighiero entitled CLL Biology and Prognosis. (Things are no doubt worse for younger patients like myself, who face the challenge of contending with the disease for several decades.) CLL takes many forms, and for every patient with “indolent” disease there is another suffering through the vagaries of therapy, the disappointment of relapse, and complications that can include uncontrollable skin cancer, anemia, shingles, and Richter’s Transformation. And did I mention death by simple infection?

Yes, on the sliding scale of cancers there are worse things to have. I’m grateful I wasn’t hit by a train, thank you. But being hit by a bus still hurts. CLL is a bitch and there’s nothing “good” about it. Even those with more cooperative cases have compromised immunity and face the stress of not knowing if and when the disease will worsen. The Dighiero report states: “Even in this very good prognosis group (Binet Stage A, mutated IgVH), progression is observed for one-third of these patients and CLL-related death for 10% of them.”

That’s for those with the very best prognostics for our “good” cancer.

"Complete response"

"Complete response" is another mind-bender. “Complete,” according to, has four definitions, of which two apply here: “Absolute; total.” And “having come to an end; concluded.”

In the ancient days of CLL, say 1996, response to treatment was determined by blood counts and physical examination, bone marrow biopsy and aspirate. Indeed the NCI Working Group Guidelines, written in 1996 and still in use today, say you have a "complete response" if your BMB still shows 30% lymphocytes. There are other criteria to meet as well: If you don't have palpable (felt by hand, as opposed to examined by CT scan) swelling of the lymph nodes, spleen, and liver; if you have no "B" symptoms such as night sweats; and if you meet certain minimal requirements for levels of hemoglobin, neutrophils and platelets -- and you maintain all these things for two entire months -- that is said to be a "complete response."

As you can see, the bar is not set terribly high, and why the doctors who wrote the guidelines chose the term “complete,” I don’t know, since all patients undergoing chemotherapy relapse, which is a clue that the response isn’t really complete to begin with. (As Homer Simpson would say, "D’oh!")

At any rate, we now have more sophisticated testing, such as polymerase chain reaction (PCR). PCR has improved our detection ability by a hundred fold, so we can now see CLL cells that we couldn’t detect before. But the language hasn't changed, so people with CLL cells as determined by PCR are still having “complete” responses.

They can call it "complete," but it's not. It's less incomplete than "partial."

And, of course, as is typical with CLL, all PCR tests are not equal; one method may provide the joyous news of being PCR negative while another determines that there are CLL cells lurking (all of this with interesting consequences for how the end results of clinical trials are determined: Did treatment X really work that well, or would a different PCR test show it to be less effective than reported?).

And, of course, future advances may change everything. PCR could be further refined or even outdated, replaced by something else. No doubt incomplete responses will still be "complete," though.

"Normal" FISH test results

"Normal" karyotype has entered the CLL vernacular thanks to the FISH test. If you don't test positive for the loss of a bit of important genetic material
(11q, 17p, Trisomy 12, 13q) on the common FISH test then you are considered to have a "normal" karyotype (genetic profile). But that doesn't mean your karyotype is normal. If it was, you wouldn't have CLL. It means they didn't test for your particular deletion and that you have one of unknown and uncharted consequence.

I have a “normal” karyotype and was lulled into thinking, for some time, that I had “passed” the FISH test. It turns out that the test didn’t test for what I’ve got; maybe it’s worse than some of the common deletions, and maybe it’s better. It will just have to be a big, fat surprise.


By now, having read this far, I can hear you thinking: Dave, you’re bumming me out! So let’s look at our last example of Orwellian doublethink, where for once the truth brings with it some hope.

The word is "incurable," and we CLL dudes and dudettes have this drilled into us so much that we take
"incurable" as a matter of faith. But there are, in fact, people who have been cured by stem cell transplants. The most famous case is that of Tom McCune, who had a transplant in 1990 and has been CLL-free ever since. "Cure" is defined by the cancer gurus as ten years without a recurrence and McCune says there are other patients approaching that mark. The fact is that most CLL patients who have had transplants have had them within the last ten years, and therefore not enough time has elapsed for the cure mark to be reached. And the most recent transplantees have benefited from advances in the procedure that will probably show a higher cure rate than McCune's generation of transplant pioneers.

A study recently reported in CLL Topics shows 75% of CLL patients who have received transplants from matched unrelated donors are alive two years after the procedure. This includes a lot of people who have been through the chemo wars, and who have “failed” their FISH and other prognostic tests. (And, as Chaya writes, “the two year survival rate is pretty close to an almost-cure, the large majority of patients who make it up to that point go on to live normal lives.” )

Another study shows that people who are in better health non-CLL wise, with no “comorbidity factors,” do even better when it comes to transplants. So for us young people who stay in shape and avoid the temptation to drown our sorrows in ice cream, vodka, cigarettes, and sloth, chances are not half bad of surviving a transplant. And therefore, there is at least the possibility of being -- dare I say it -- cured?

Of course, transplants are very tricky and very hard on the body, not a choice to be taken lightly. You still need the right donor match, and nothing is a sure thing, and the cure still might kill you. But the odds are getting better, and will only continue to do so as transplants are further improved (which will only make them easier for older patients, as well).

So, to sum up, CLL is a bad cancer that chemotherapy cannot remit completely, the victims of which have abnormal genetics. And some of them can be cured.

Now, about that drink . . .


For a new report on transplants by the leader in the field, Dr. John Gribben, follow the link below. Gribben cautions that "the follow-up of most clinical trials is too short to assess whether the use of SCT can cure CLL," but the report has some encouraging statistics mixed with some cautionary ones. The light at the end of the tunnel may be the light at the end of the tunnel, or it may be an oncoming train, depending on your individual response to a transplant:

Read more on how transplants could save your life, including ways to increase the odds in your favor:

Who is Tom McCune and why is he smiling?:

CLL Biology and Prognosis by Guillaume Dighiero:

If you want to poke around a website that discusses language as used by Orwell –- and today’s continuing abuses –- visit the Newspeak Dictionary at:

Thursday, November 24, 2005

What's in a name?

I have leukemia, so what does that make me? Am I a leukemia “patient”? Or a leukemia “victim”? Or a leukemia “survivor”? Or am I just a dude with leukemia -- i.e., a person, one of whose qualities, but by no means the whole person, is an unwelcome compulsion to create a vast amount of mutant B cells?

As people with CLL, we are often pigeonholed by society’s stereotypes and expectations about cancer. The media reflexively uses various terms, without thinking about them much, and we have all encountered friends, family, and coworkers who see us as something different than what we were before we were diagnosed.

There is no doubt that the diagnosis of a life-threatening illness can change us, sometimes even for the better. But people who aren’t walking in our shoes may have a tendency to play fast and loose with labels, slapping them on us when they don’t always fit. There is a danger in mindlessly accepting them, in subtly becoming what others expect us to be.

So what should we call ourselves?

I don’t really like the description “patient.” There is a certain loss of individuality in that appellation, a cow-like aspect that implies being a member of a rather passive herd of unfortunates managed by person
nel bustling around in white coats. It makes me a set piece on the medical stage, one player in a long row of sufferers tethered to IV poles, and it brings with it all the notions of powerlessness that one ascribes to such an image: less power over disease, and less of a voice in the “doctor-patient” relationship. Medical care is part of the CLL experience, but not everything about it (though I certainly prefer “patient” to “medical consumer”).

Despite my reservations, “patient” is not inaccurate, but it is just one of the hats we wear. And perhaps we need to dust it off and change the way “patient” is perceived, make a transition in public perception from “poor things” to “hell-raisers." (Movie trailer for Bone Marrow Biopsy II: Aspirate This!: "Their white cells make them see red!”)

It should also be noted that the word "patient" does have an unintended meaning: With CLL, one must learn to be patient. That’s not the usage intended, though.

“Victim” is bad on so many levels. You can be a victim of anything, if you choose to see life that way. As a child, I was a victim of candy manufacturers, consumption of whose products required multiple fillings in my teeth. When I was 16, I was the victim of not having a car. You get the idea –- “victim” is overused, which tends to dilute its meaning for those who are genuine victims, such as babies killed by bombs. The decline of the human body is part of living -- I have been heading toward destruction since I left my mother’s womb one autumn day in 1956 -- and while this is an unfortunate progression, I do not see myself as a victim of the natural order of things. Yeah, I feel sorry for myself sometimes. But I have the power to fight back. Victimhood is not empowering, and I have always found it to be a most unpleasant way of getting by.

“Survivor”? Sometimes you see a CLL person who is rather proud of this title, and I can see why. Some people go through a hell of a lot, they surprise themselves, they prove something to themselves, and perhaps to others. I take nothing away from their accomplishments and they deserve to wear the title proudly. For some people, those with aggressive disease or other complications, CLL is a hard struggle from the start.

But, taking a broader view, we are all survivors until we die, whether we have leukemia or not. To me, unless I have truly earned my stripes, been to the edge and back, it is not right to adopt it as a label, because survival is just part of the act of living. Anyone alive is a survivor, really. And a philosopher I know suggests to me that since CLL is chronic, do we really survive it? Or do we survive along with it?

Speaking of “Survivor,” one cannot help but think of the CBS TV reality show of the same name. The motto of the show, in which contestants are pitted against one another in a remote place, usually a tropical island, is “Outwit. Outplay. Outlast.” In a strange way, that just about sums up the battle many of us have with CLL. A few false mov
es, a streak of bad luck, and you can get voted off the island, which is not a pleasant prospect. Play it right, choose treatment wisely, get a little lucky, and you just might make it to the end. There’s no million dollar prize, but life itself is infinitely more valuable.

That leaves us with “dude.” I like the blend of serious and casual that comes with “leukemia dude.” It is unexpected; it is impossible to conjure up a stereotype of how a leukemia dude looks or acts, and it breaks through the fog of negativity that others can mentally impose on those with our condition. If “dude” implies a somewhat looser, going-with-the-flow approach to life, even someone who’s cool, then maybe we need to add that element to the picture that others have of us.

Of course, you can just be a little less trendy and say “person.” That is what I still feel that I am, something whole and unbent, not a stereotype or a role or a sound bite. I have hazel eyes and a brown cat and a silver car and some extra white cells.

The phrase “CLL’er” has been used on occasion. It’s a bit flip, perhaps, but rather neutral. I don’t mind it. Taking a page from ethnic descriptions, there’s also “Leukemic-American,” or “Leukemic-Canadian,” and so on. And at times I feel like one of the “Leukemically Challenged.”

Though I’m not sure quite what to call myself, I do believe in the power of language. We are what we tell ourselves we are. Let us not forget that we are whole, made up of many things, and that CLL may be part of us but it is not everything about us.

Tuesday, November 22, 2005

Diagnosing your doctor

As my adventures with Dr. Lippencot and her new office partner demonstrated, the choice of a doctor is crucial in helping patients deal intelligently with CLL.

But when it comes to doctors, otherwise intelligent people sometimes see their good sense fly straight out the window. Doctors may offer the keys to salvation, after all, and some patients tend to be sheepish in their presence, regarding them with the obeisance normally reserved for deities. Religious matters aside, many people simply feel ignorant about the disease and how it works -- not to mention overwhelmed by the shock of their diagnosis -- and therefore embarrassed or at a loss to question what they are told.

Fortunately, the internet provides us with the opportunity to learn, quickly, what we need to know. And that leaves as our only excuse the not wanting to know. Sometimes I hear a patient say: “I let my doctor do the driving because it is too much for me to handle.”

I am reminded here of Toonces, the Cat Who Could Drive a Car. This was a gag on Saturday Night Live in which a gray tabby cat takes the wheel and successfully ma
nages to stick to the road for a few seconds before plunging himself, and his smiling human passengers, over a cliff.

The point I am making is that doctors are people, not gods, and they make mistakes in judgment, especially about tricky diseases like CLL. And they are busy, and not always up on the latest treatments and prognostic tests.

Even CLL experts, at a CLL Consortium institution, can still drive you over a cliff.

So, without further ado, please go to CLL Topics and read the article I wrote there called “Diagnosing Your Doctor.” Here’s the link:

(And for those who want to take a spin with Toonces, go to YouTube.)

Saturday, November 19, 2005

My adventures with Dr. Do-little, or how I narrowly avoided the wrong treatment and learned a lot of big words

Dr. Lynn Lippencot had deep blue eyes and gentle wrinkles born of age and experience, with gray hair swirled about her head in some sort of styling afterthought. She was busy, as was her staff, and her office was so harried that it always seemed to be one patient away from gridlock. Yet in the few minutes allotted for my appointment, the doctor managed to find a sense of calm, a momentary focus, and she exuded reassurance. This is what a new patient wants.

Her chemo infusio
n room, arrayed with oak bookshelves and overstuffed recliners with a magnificent view of the local scenery, even looked like a not unpleasant place to be. I recall, after my first visit to Lippencot in October 2003, thinking: This won’t be so bad. I envisioned bringing my lunch, catching up on my reading as the infusion proceeded, perhaps laying back for a nap as I watched the sun wash across the cliffs in the distance. Of course, I’d have rather avoided the whole thing, but everyone was telling me I had “the good cancer,” and there was nothing to worry about.

The doctor was certainly upbeat. My CLL had been discovered during a routine blood test the month before, and a subsequent flow cytometry test had come back, indicating I had what she called “garden variety CLL.” Sort of like a weed, I guess. Fortunately, I had no “B” symptoms such as fatigue or night sweats, and my platelet and red blood cell production were normal, two important factors that normally argued against starting treatment. Even a fairly high lymphocyte count, 130,000, was no cause for jumping into therapy.

But a CT scan showed a number of lymph nodes throughout my body enlarged up to 3 cm. My spleen was at 18 cm. I didn’t really know what these numbers meant, and only later would I figure out that the swelling, while of some concern, was not nearly as bad as ma
ny patients experience.

The doctor was worried, though, that a swollen node could “cut off a kidney” by
closing a bile duct. Visions of kidney failure loomed, and therefore treatment was advised, she said. I could take a pill called chlorambucil, which was an older therapy, not exactly on the cutting edge, and would take some time to work. Or I could opt for fludarabine, which she described as “well-tolerated, with an acceptable toxicity profile.” Fludarabine was the “gold standard” of treatment, and it would work quickly and effectively. “I have one patient who’s been coming in every few years for ten years and getting fludarabine and he’s still going strong,” she said, reassuringly.

Dr. Lippencot would have preferred a decision from me then and there, but I asked for a few days to ponder the choices. On my way out of the office I was handed the “leukemia packet” of booklets about CLL and chemotherapy, including one produced by Berlex, the makers of “Fludara for injection,” trade name for fludarabine. On the cover there was a drawing of a woman, one hand resting on her chin, as if she were deep in thought, though not overly concerned.

It was a brave new world, but it seemed as if I would be well taken care of. Indeed, if I had only just go
ne along, my life would have been easier.

But probably shorter.

Cartoon chemotherapy

The Fludara booklet was written at about an eighth grade level and was filled with cartoon drawings, one of which pictured B cells as looking like the monster in The Blob, a '50s horror movie classic. The booklet addressed issues of hair loss and nausea, which I had always assumed were the worst effects of chemotherapy. I could handle that, especially since I had already been losing hair for years and had gotten past my fears of baldness.

But tucked into a flap in the back was the actual “package insert,” a single page with printing so small that it almost required an electron microscope to read it. Some things caught my eye. Fludarabine could be mutagenic; it could cause a coma; it leads to neutropenia, thrombocytopenia and anemia in a majority of patients; I had a 16% to 22% chance of coming down with pneumonia. There was more. And even if I wasn’t sure what all those things meant, they sounded serious enough to break through the pleasant fog that had surrounded me since leaving the doctor’s office.

The fog continued to lift as my wife, Marilyn, and I began to poke around the internet, finding further studies that raised more red flags. Indeed, the more we learned, the more we realized that there were serious questions surrounding the side effects of chemotherapy. Hair loss and nausea had nothing to do with it.

Nonetheless, with my kidney ostensibly resting uneasily beneath the Lymph Node of Damocles, I remained focused on treatment. After all, my oncologist said I needed it. And my expectations were at work, too – when you have cancer, you try to kill it. That’s what I’d always been led to believe. It’s natural, when you’re newly-diagnosed and scared, to want to do something to get as much of the CLL out of your body as possible. And this dovetails into the disposition many oncologists have to treat, even when not treating, or treating less, may be a better idea. (The "watch-and-wait" concept of doing nothing was counter-intuitive, at least at that point in my education.)

It wasn’t long before I stumbled across an interesting treatment prospect, outlined in the Spring 2003 Leukemia Insights newsletter from the MD Anderson Cancer Center in Houston. The article, accompanied by a photo of a bearded and beaming Dr. Michael Keating, who also looked full of experience and reassurance, reported that a new combination of rituximab, fludarabine, and cyclophosphamide (RFC) had a 69% “complete response” rate in previously untreated patients. (Eventually, patient reader, I will post in detail about “complete” and other responses in CLL; as usual with this disease, things are never as they seem.)

If I had to do chemo, RFC made better sense than fludarabine alone, which had a much lower response rate. Indeed, the very important fact that there was only a 20 percent chance that fludarab
ine would provide me with a “complete response” had been ignored by both my doctor and Berlex. When my doctor called to ask me what I had decided, I told her about RFC, which seemed to me to be a promising discovery.

“Oh, that,” she said. “I tried that with someone and he ended up in the hospital on a ventilator.”


“Let me think about this some more,” I said. “I’ll get back to you.”

No easy choices

The more Marilyn learned about the side effects of chemo, the more she threatened to break my kneecaps if I ever decided to leave the house for treatment. Indeed, the evidence began to mount that some side effects could in themselves be life threatening. I realized that there were s
ome unlucky people who were, evidently, done in by their treatment. Remissions were followed by fatal secondary cancers, bone marrow was so compromised that it became “dead” and the patient had no immune system left. Simple infections could then prove fatal.

Some time later we learned that fludarabine has been shown to give a free pass -- at your expense -- to the worst type of CLL cell, the one with the 17p deletion. Bear with me for a minute, if you're interested in further proof of the theory of evolution: CLL cells are wonky little buggers, deformed as a result of chromosomal abnormalities, some of which doctors have recently become familiar with. There is a test called FISH (Flouresence In-Situ Hybridization) that checks for the more common abnormalities. The worst of them is what’s called the 17p deletion, which carries with it a much shorter median survival for the patient than any other prognostic indicator in CLL.

In a nor
mal situation, thanks to a functioning “TP53”gene -- where the 17p is located -- cells have a mechanism by which they can tell themselves to die. This death is called "apoptosis" (or perhaps "Apophis," for confused Stargate SG-1 fans). Every CLL patient most likely has a few B cells with this deletion or that, including 17p. (The FISH test only puts up the red flag when a high percentage of cells tested show a particular deletion, about 20% being the problem point for 17p.) A few out of billions isn't going to matter, usually, since they all compete to survive, often preventing the worst one from predominating. So along comes fludarabine, which relies on the 17p function to do its job, to tell the cell to die. It kills off those CLL clones with functioning 17p. And what doesn’t it kill? The ones where the 17p is deleted, the very worst ones of all. The other clones having been eliminated, the bad boys now have the field – your body – to themselves. Very Darwinian.

This danger is mitigated somewhat by adding other agents that don't rely on 17p, s
uch as rituximab, to fludarabine therapy. Indeed, there is a more-is-better school of thought when it comes to chemo, if you can get past the potentially life-threatening toxicities. But those should not be taken lightly, especially if your back isn't to the wall. It now appears, for example, that the use of fludarabine and immunosuppressive combination therapies such as RFC may be implicated in the overall rise in cases of Richter’s Transformation; this is where the disease takes a nasty turn into large cell lymphoma, and the median survival time is less than a year.

I had to weigh the choices: If there was a chemo regimen that could guarantee a cure, or at least a very good chance of one, it might be worth taking the risks. But there’s a reason it’s called a chronic disease: chemo can delay it but it cannot stop it. And while there certainly are cases where aggressive chemotherapy is absolutely justified, I had to wonder if mine was one of them. Remember, the main reason for treatment at all was "cutting off a kidney." The only prognostic test I could get at that time -- just two years ago but eons past in terms of available prognostics -- was CD 38, which showed me at 12%, and therefore "negative," and therefore ostensibly with less aggressive CLL.

Still, if I needed treatment, then I had to do something. So we continued our resea
rch, trying to absorb as many big words and new concepts as we could while my oncologist fidgeted nervously in the background, visions of exploding kidneys dancing in her head. As it turned out, the more we looked into things, the more we learned that my doctor’s concern about the kidney was highly unusual. We began to suspect that despite charging more than $400 per 10-minute visit, we might not be getting our money’s worth, or our insurance company’s money’s worth, when it came to her CLL expertise.

The worst word in the English language

Meanwhile, we ran across something else to be concerned about, a simple word that Berlex failed to mention anywhere and that my doctor had also avoided: refractory.

"Refractory" is my least favorite word, and that’s quite an accolade, since there are
so many to choose from. Removing the side effects issue from the discussion for a moment, if chemotherapy was guaranteed to work every couple of years ad infinitum, then we’d already be at the point where CLL is a controlled disease. But one of the problems is that nothing works forever. Patients can become refractory to a drug, which means the drug won’t work on them anymore. Almost everyone becomes refractory to fludarabine, for example.

This came as a rude shock, something that drug companies and doctors don’t really like to discuss and that patients don’t like to hear. The guy that Dr. Lippencot said had been on fludarabine for “ten years and going strong” was probably skating on very thin ice at this point.

Out of this discovery about “refractory” came some crystal clear logic that began to guide my treatment decision:

Use a drug today when you don’t need to, and that’s one less time you can use it in the future. You only get so many chances with the various drugs that are available, and you’ll likely have no idea how many chances you’ll get with any given one. Don’t burn any bridges before it is wise –- or at least unavoidable -- to do so.

Google does good

One night I decided to investigate this rituximab stuff (trade name Rituxan) that had been so instrumental in the apparent success of the RFC protocol at MD Anderson. I did a Google search and ran across CLL Topics for the first time. Suddenly another side of the story came into view: Rituxan as a single agent, or "monotherapy." Here was this retired chemist named Chaya Venkat, who was reinventing the wheel in an effort to save her husband’s life, saying things like, “Be smart in making your therapy decisions, play for time and stay as healthy as possible in
the meanwhile. Live to fight another day when the odds are even more in your favor.”

That made sense.

It was also heartening to see that someone out there with absolutely no vested interest in the cancer business had begun to intelligently deal with all the issues that Marilyn and I had been wondering about: toxicity, effectiveness, what to do and when to start, what tests to have and how to get a handle on where my disease really stood.

As I perused Topics I began to get a better grasp of the science, and I saw a little light in the darkness: Rituximab is a monoclonal antibody (thus the "mab" in the name) created from mouse cells. It is designed to bind to the CD 20 receptors on human B cells, and creates an antigen-antibody complex that signals to the body's immune system that we are being invaded and need to fight back. The body -- through such things as neutrophils, NK cells, macrophages, and a mysterious soup called complement -- assists the Rituxan in the cell kill. There are few downsides for most people, usually the worst being that Rituxan also tags normal B cells as well. CLL patients still have a few of them, and their function is important, so one is left with some immune weakness during and after Rituxan therapy, though this pales in comparison to what chemo drugs do.

Rituxan works well in non-Hodgkin's lymphoma, where CD 20 levels are usually over the top, and I read on Topics that it also seemed to work fairly well on some CLL patients, especially those with highly-expressed CD 20. Excited about the prospect of finding a treatment that would possibly control my CLL with minimal side effects, I went immediately to the file cabinet and pulled out my medical records. I knew I had been tested for CD-this and CD-that. And there it was, CD 20: Moderately bright, expressed on 92 percent of cells.

I was a go
od candidate for Rituxan monotherapy. There was a way out. (And for those of you who, on the surface, may not be such good candidates, don’t get discouraged. It seems to work pretty well in some people with “dim’ CD 20, too.)

Jumping the SS Lippencot

On my next visit to Dr. Lippencot, I discovered that she was actually afraid of Rituxan. She didn’t want to use it, either alone or in combination with anything else. It might, she asserted, "crum up" my kidneys. Indeed, in the very early days of Rituxan's use in CLL, doctors sometimes did not anticipate the high degree of tumor lysis, or cell die-off, that would result. This did lead to kidney problems in a few patients. But with adequate precautions -- taking allopurinol, drinking a lot of water, slower infusions over more days, even leukepheresis -- this is now a dead issue, and should have been in late 2003, also. I had to wonder, following the ventilator story she had told me, whether another CLL patient was now on dialysis somewhere following her administration of Rituxan.

Finally, Lippencot resorted to pulling out tricks at random. My insurance, she claimed, might not pay for Rituxan (not that she'd asked them, and she was wrong). Reservations about chemotherapy are the products of "fear-based thinking," so I was a misguided wuss. Fludarabine, in her experience, "works repeatedly." Noticing my lazy right eye, she posited that it could be the result of CLL getting into my central nervous system (highly unusual, by the way). Finally, she exclaimed, "I've been doing this for a lot of years!"

What I learned was that she had her comfort zone, which started with chlorambucil and ended with fludarabine. Her self-limitations were limiting my choices, and compromising my medical care. Ultimately, she could do little for me.

Sensing that my balkiness would not be easily overcome, she had me see her new partner, an oncologist whom, she volunteered, "has had a lot of experience with CLL." It was his first day at work, and he did what any good business partner does: stood by her decision tooth and nail.

Our conversation started badly and then devolved. He spat out various acronyms of older therapies that he was familiar with -- CHOP and COP and so on -- and ended up by insisting that fludarabine was "all you need." Rituxan, comparatively mild and already demonstrated to add enormously to the effectiveness of fludarabine therapy, was out of the question. When I mentioned using Rituxan by itself, I may as well have been yelling "The power of Christ be upon you" at a demon-possessed child. “Rituxan is not standard therapy for CLL!” he repeated at least three times, his voice growing more shrill and his face growing redder. If he could have rotated his head 360 degrees while spewing green slime, he probably would have done so.

Finally, like my Jewish grandmother, he ended up warning: “You could end up in the ER here with kidney failure! Is that what you want to happen?”

Armed with the power of information, Marilyn and I knew that it wasn’t going to happen, and we knew this would be our last visit to this office. On the way out we passed the pleasant infusion room with the spectacular view. It had now taken on an almost sinister aura, and we were glad to be done with the place.

A room without a view

Through patient networking I managed to find an open-minded oncologist a couple of hours away. She was younger, down to earth, pleasant but hardly the touchy-feely type. Lippencot had initially exuded an enveloping sense of calm, until my kidneys got the best of her; my new doctor was pretty much all business. I realized that bedside manner is not the end point of treatment, and I was grateful to have found someone familiar with recent advances in CLL therapy.

The new doctor was open to RFC, and I considered it. It was then, and is now, a new treatment, its track record being written as we speak. There was no way of knowing how long a remission might last, assuming I had no nasty complications. Even a best case scenario -- maybe five years? -- didn't answer that eternally nagging question in CLL therapy: Then what? So I opted for the less dramatic but safer and to me more logical choice: Rituxan alone. RFC, or the next generation of combination chemo, would always be there if I needed it.

We decided to proceed with Rituxan sooner rather than later because my disease had progressed to the point that Rituxan’s effectiveness might be significantly diminished if I waited much longer. The more impacted lymph nodes, and the bigger they are, the harder it is for Rituxan to get into them and do the job.

It was a fine line to walk, of course. I had possibly set the clock ticking on Rituxan’s usefulness in my case, though the jury is still out on if, and to what degree, CLL patients become refractory to it. But I did not want to let my disease get to the point where I would have no choice but to use something more heavy-duty. I was playing for time and it was a calculated risk, which is the name of the game in CLL.

My new doctor’s infusion room was about as inspiring as a bus station, but I didn’t mind. After the first infusion, my absolute lymphocyte count dropped from 157,000 to 9,900. The second week saw my spleen empty out. By the time I was done with eight rounds of Rituxan, my lymphocyte count was down to 2,300. My spleen appeared to be normal, and most lymph nodes were as well. It hadn’t been so effective on a few, and I knew going in that Rituxan doesn’t clean out the marrow like some of the tougher chemo regimens do. But it also doesn’t have the long-term negative effects, and I had not engaged in any significant bridge-burning.

I felt, as I left the office following my last treatment, that I had done the right thing. Everyone in life has their regrets; I am glad that when it came to this life-and-dea
th matter, I had none.


A year and a half later, when the IgVH mutational status test became widely available through Quest Diagnostics, I found out that my decision to avoid single-agent fludarabine was a good one for another reason: I am unmutated, in that unfortunate group whose CLL tends to reproduce more quickly. But I also have a “normal” FISH result, with no deletions in crucial chromosomes such as 17p and 11q, and this has probably kept the disease reasonably well-behaved up to now. Had I followed Lippencot's advice and used fludarabine alone, there is a decent chance that it might have selected for CLL cells with the worst deletion possible – 17p – leaving me with a recipe for the worst form of CLL: a bad karotype and unmutated. And likely a lot less time on the planet.

I also discovered after the fact that Dr. Lippencot had been pushing fludarabine knowing full well that a blood test had shown that I was "Coombs positive." This means I have developed antibodies to my own red blood cells, not a pleasant thought, and therefore am more prone than average to develop a full-blown case of autoimmune hemolytic anemia, or AIHA, which is no walk in the park. Even the cartoon booklet published by Berlex mentioned this one. The Mayo Clinic, in its latest standards and practices of care, cautions against the use of fludarabine in such patients, as fludarabine can trigger AIHA. Even though I was no longer Lippencot's patient, I dropped a copy of the Mayo article off at her office, hoping against hope that she might, through some miracle that would rival the parting of the Red Sea, absorb the information.


For more about the current state of CLL treatment, and for some very interesting comments on fludarabine refractory patients – and that means you, eventually, if you use it – read this article by the highly-respected Dr. John Byrd and others:

You can read about the Mayo Clinic's "Current Approach to Diagnosis and Management of CLL" at:

For more about prognostic testing, such as the IgVH mutational status and FISH tests referenced above, check out this link at CLL Topics, which also contains links to other articles about prognostics:

Vis-a-vis the question of immunosuppressive therapy and Richter's Transformation, there is an abstract here:

I will post more about the pluses and minuses of single-therapy Rituxan, as well as combination chemotherapy (there is an interesting and important debate over RFC). Figuring out what kind of CLL you have, and what to do about it, is the main task that patients face.

And, yes, Lynn Lippencot is not her real name.

September 3, 2003: Diagnosis Day

I was having an odd dream during the early morning hours of September 3, 2003. In it, Marilyn and I had a loft apartment in a big city, and we were hosting a party during which we were showing off some modern art on the walls. At one point, I found myself sitting in a chair and was about to stand up when one of the guests said, “Don’t try to stand up! You’ve had too much to drink.”

That’s odd, I thought
to myself in the dream, I haven’t been drinking. This contradiction brought me to consciousness, and even though my eyes were closed, it felt like the room was spinning, as if I had actually been drinking. It was an odd sensation, and not a pleasant one, and I wasn’t sure if I was still dreaming, or if I was waking up.

I opened my eyes and the room was, indeed, spinning. I felt nauseous. This had
never happened to me before, drinking or no. Slowly I managed to sit on the edge of the bed. The chair opposite was moving gently, up and down, as if it were on the deck of a ship. One grows used to the idea that one’s eyes always tell the truth, and that the signals they send accurately help direct the movements of the body. It is scary when, after half a lifetime, things go haywire. When I stood up, I was unable to walk straight, and had to grip the walls to make it to the bathroom.

Just give me a minute, I thought to myself. I can figure out what is going on.

I am not a panicky
type, nor am I a hypochondriac. Until that morning, I had seldom visited the doctor. I had graduated with honors from the school of It’s No Big Deal, I Can Get Over It. And indeed, whether I had a cold or hay fever or a bad headache, I had always managed without too much fuss. I could even handle minor dentistry without novocaine.

But I knew, as I looked in the bathroom mirror that morning, that I was not going to feel better from this without some help. I was turning whiter than white and sweating profusely. Am I having a stroke? I wondered. I was almost 47 and out of shape. I puked in the bobbing sink and then sat on the toilet for a few minutes, watching in the mirror opposite as sweat cascaded from m
y wet hair down my face. It was not getting better.

I gathered my sea legs and made my way back to the bedroom, where I woke Marilyn, and she drove me to the emergency room. I held a wastebasket in my lap, into which I continued to pour whatever I had eaten the night before.

I was immediately admitted to the ER and escorted to a bed, where I was suitably engowned and then hooked up to an IV bag of Phenergan, which for the next hour appeared to me to be the single greatest invention in the whole history of mankind. Slowly, as the drug suffused through my veins, the nausea began to vanish, the walls began to straighten, the ceiling lights assumed a fixed position in the acoustic-paneled firmament.

Marilyn sat to my right, holding my hand. The doctor would have to run some routine tests, but it wasn’t a stroke. I would be home by noon. They marched me through some X-rays. I was hooked up to an EKG. Some blood was drawn. The curtain to our cubicle was pulled and we waited, secure in the knowledge that the emergency was growing less acute as the minutes went by.

It gets worse

After a short while, there was a rattle as the curtains were drawn back. A thin, gray-haired nurse walked in, a little too rushed and businesslike.

“Have you ever been diagnosed with leukemia?” she asked.

“No,” I responded, as a knot began to grow in my already overworked stomach. The nurse turned and left us, abruptly, on her way to something important.

Marilyn squeezed my hand. We looked at each other.


Neither of us knew much about it, except that we knew it was something that affected children, and w
e assumed it was usually fatal.

I fought off a tendency to think that it can’t be true. Laying in a hospital bed, exhausted from my vertigo and vomiting, was proof enough that something was wrong with my body. My survival instinct kicked in, and I somehow found the strength to hold it together and deal with the news. There would be no rest, no welcome dozing, no letting go.

Tears began to creep down Marilyn’s face. Abruptly awakened from very little sleep, she had been coping with the unknown all day; now circumstances had forced a new role upon her, one of a helper who often feels helpless, a watcher of fate. There would be no going back to that morning before my dream, or to last night, or to last year, or to any time when health could be taken for granted and life could be lived as if there would always be another tomorrow.

A young orderly c
ame in, fresh-faced and well-scrubbed, as if minted from some technical school for medical assistants that is advertised on afternoon TV. He proceeded to tell me, in almost breathless and excited tones – as if this were making his day – that my white blood count was 144,000, and that normal was somewhere between 4, 500 and 11,000. He said something about lymphocytes, which in my case accounted for 129,600 of the total, and then prattled on about other types of blood cells that I had barely heard of. I had not had a CBC -– complete blood count -- in seven years, thanks in part to changes in health insurance that tended to obstruct, rather than enhance, medical care. I’d had my cholesterol checked a couple of times at health fairs, and I’d even donated blood the previous year, for which they perform a rudimentary screening, but not for leukemia. Being middle aged, I had assumed heart issues were my primary concern, and that there was little value in a full blood panel.

In retrospect, as I will explain more fully in another post, my ignorance was probably a blessing.

The longest ten minutes, ever

The doctor came in and the orderly left, wheeling the EKG machine away, undoubtedly off to phone his friends with the news that, dude, this guy is full of like, lymphocytes.

The doctor was about my age, white-coated, with reddish hair and a pleasant manner that did not diminish with the news. Yes, she said, it appeared that I did have leukemia, and they needed to find out what kind I had. If it was an acute case, I would need to go to a hospital immediately (I was at our small town’s medical center, which is affiliated with larger hospitals in the area). If I had a chronic case, I could just go home.

My vertigo, she said, was probably “just” labrynthitis, an inner ear infection of unknown origin and for which there is no particular treatment.

“Is it caused by th
e leukemia?” I asked.

“Probably not,” she replied. And then she paused. “Well, I suppose it could be caused by one of the acute forms.”

Something spiked in me. Blood pressure? Stomach acid? Adrenalin?

My blood had been sent down the hall to the office of Dr. Lynn Lippencot, a hematologist/oncologist, which means a blood doctor/cancer doctor. She would look at it under a microscope and let us know what kind of leukemia I had. If the blood was full of tiny blast cells, it would mean acute. If it was full of larger but immature lymphocytes, it would mean chronic. It would take ten minutes or so to find out. The ER doctor went back to her other duties, leaving the curtains open.

Marilyn and I tried to hold a conversation about the merits of, worst case scenario, having to go to Hospital A or Hospital B. Tears ran down her cheeks. The real conversation, the one we didn’t need words for, went like this:

I love you and I am so sorry.

I love you, too.

We held hands in silence, and we waited. And waited.

The "good news"

We could see the doctor from our cubicle, sitting at the nurses’ station when the call came in. “Excellent!” she yelled, punching the air with her pen. She came back into the room.

“You appear to have chronic” -- she stumbled over the next word – “lymphat – lympha -- lymph-o-cytic leukemia

“This is good n
ews, in a way,” she went on. “It’s the best leukemia to have. It’s very slow-moving, and most people die with it, not because of it. In fact,” she added a little sheepishly, “some people call it a good cancer.”

Marilyn and I squeezed hands again. I would be going home. And it looked like I might not be dead next week.

The doctor went on to tell me that CLL was something I could live with without much trouble, and that they even had a doctor on the staff who had it.

She felt the lymph nodes in my neck -- “yes, I can see they’re enlarged” -- and reported that the X-rays done earlier showed that my spleen was a little swollen.

“Don’t worry,” she said cheerily. “You can always have your spleen or your lymph nodes taken out.”

The doctor breezed off to process my discharge papers as I got dressed. On my way out she handed me a prescription for more Phenergan and relayed the message that Dr. Lippencot w
anted me to set up an appointment.

But there was one thing I couldn’t get out of my head:

The best leukemia? A good cancer?

I remember thinking, as I left the ER with my wastebasket in tow, that the day had become every bit as surreal as my dream.