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 café 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!

Faith

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.

RESOURCES

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

http://en.wikipedia.org/wiki/Agnostic

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

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.

RESOURCES

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

http://tinyurl.com/78ktd

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

http://www.clinicaltrials.gov/ct/show/NCT00166335?order=1

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

UPDATE

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

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.

Please.

RESOURCES

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:

http://www.asheducationbook.org/cgi/content/full/2005/1/285

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 dictionary.com, 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.

"Incurable"

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 . . .

RESOURCES

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: http://www.asheducationbook.org/cgi/content/full/2005/1/292

Read more on how transplants could save your life, including ways to increase the odds in your favor: http://www.clltopics.org/BMT/OnlyRealCure.htm

Who is Tom McCune and why is he smiling?:
http://www.mccune.cc/CLL.htm

CLL Biology and Prognosis by Guillaume Dighiero:
http://www.asheducationbook.org/cgi/content/full/2005/1/278

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:
http://www.newspeakdictionary.com/