My Christmas lump of coal

On the eve of Christmas Eve I had a little too much egg nog with brandy. One thing I have learned over time is that alcohol really does thin the blood, so to speak. Indeed, studies show that low hemoglobin can accompany chronic alcoholism. My excuse for low hemoglobin is autoimmmune hemolytic anemia resulting from my CLL (though if life keeps getting more stressful I may decide to add chronic alcoholism to the list).

Hemolysis, in which the body destroys its own red blood cells, is the thing to watch for in AIHA. It can come on suddenly, and over time I have become adept at looking for the signs and signals. Catching hemolysis early on is essential to keeping it in check. The more it begins to snowball, to use a seasonal metaphor, the more it can get out of control, requiring tougher steps to control it. Oh, and there’s that little thing about putting your life in danger as your body runs out of red blood cells. You never want that particular Elvis to leave the building.

If there is a decline in my hemoglobin, the first thing I usually notice is a pounding in my ears. What I’m hearing is my heart pumping away, and when HGB is really low, it’s like a marching band. When HGB is just a bit low, it’s like an occasional lone drummer offstage. When HGB is normal, I don't hear it at all.

Well, the Little Drummer Boy was busy as I tossed and turned in bed a few hours after placing my nog-drenched frame in the prone position. The easiest way for me to tell how my HGB is doing is to drink a lot, then go to bed. That’s just one of the tricks of the AIHA trade that your doctor probably won’t tell you about.

Sure enough, blood tests the next day -- I have that holiday miracle, a doctor who answers her cell phone on Christmas Eve -- confirm that I’m hemolyzing again. On Dec. 2 all my red counts were normal. Twenty-two days later the HGB was down to 11.6 (from 13.5), the MCH and RDW were high, and overall RBC was 3.66, down from 4.47. My LDH, which measures turnover of cellular activity -- as in red cells being chomped by macrophages -- had gone from mid-normal to high-normal, and total bilirubin was now at the very top of normal, meaning debris was moving through the liver.

Results of the Direct Coombs, haptoglobin and reticulocyte tests will have to wait until Friday or Monday. But based on past experience, what we have here is active hemolysis, not quite out of control but definitely past the Miss Manners stage of fine macrophage dining.

So, hello Decadron. Hello, doctor next week. Hello, chemo very soon.

And hello, CLL curveball. As they used to say on Monty Python, “Nobody expects the Spanish Inquisition!” We CLLers with active disease had better learn to expect it at any time, and that includes holidays.

Ataraxia

I ran across the word “ataraxia” a while back and I liked it. Not only for the way it rolls across the tongue (at-uh-RAK-see-uh), sounding like so many things: an exotic city on a distant continent, a make-believe world conjured by a child, a potent drink that promises to liberate the soul.

No, I also liked it because of its meaning, from the Greek ataraktos, or “not disturbed”: A state of freedom from disturbance of mind. Calmness untroubled by mental or emotional disquiet

Faced with the ever-shifting challenges of the “new normal” that is life with chronic lymphocytic leukemia, ataraxia is something that we patients and caregivers often find lacking in our lives. We crave calmness of mind. Every bad test result or new symptom is a reminder of just how far we can find ourselves from peace and serenity.

It is therefore no surprise that ataraxia is hard to come by in CLL, as the Mayo Clinic has officially found -- I do believe this disease would present something of a challenge to the coping skills of the Dalai Lama. But nothing is impossible, and I sometimes find vignettes, little triumphs of the spirit that show ataraxia is possible in the face of adversity:

A caregiver, whose husband is in ill health and responding poorly to chemotherapy, wakes up to find that her cow broke through a fence and ate her carefully-tended garden. After she cries her eyes out, she and her daughter go out and buy new plants and, together, start all over again. In replanting, she finds strength.

A patient, who has bad prognostics and is undergoing tough chemotherapy, feels like crap. But he loves to cook, and he cooks a dinner for his wife and their two closest friends. At the end of the night they shoot off fireworks.

A man in his 50s, having fought aggressive CLL with aggressive therapy, including a failed stem cell transplant, rides out into the desert on his motorcycle and plays his guitar, composing songs amid the windswept rocks.

A young mother, whose disease has transformed to something worse after chemotherapy, is in hospice care at home. She is in pain, lymph nodes are pressing on her, but her husband buys her a new coat and the two of them and their three-year-old daughter go to the beach and play in the sand and the waves.

There are more stories like these. I like to keep them in mind. Those of us touched by CLL quickly learn that life is fragile, but these stories also tell me that the will to live is strong and that we are resilient. That at times, even in the worst of times, we can reach ataraxia.

My visit to the NCI, Part 2 - The expert consensus on transplants

Readers will recall that in Part 1, I had approached the National Cancer Institute about a transplant clinical trial, a possible donor had been identified, and I was asked to meet with a transplant doctor to determine what to do next. Marilyn and I set out from Arizona on a road trip to Bethesda, MD, where the NCI -- and possible salvation from CLL -- awaited.

Tucked under the passenger seat of our Prius was a black folder stuffed with articles and studies that weighed the risks and rewards of a transplant. Taken together, Marilyn and I hoped they would help provide an answer to the question: When is a transplant a good idea, and am I at that point? At the very least, we hoped to learn enough to be able to walk into the NCI and have an adult conversation.

The day before our meeting in Bethesda, we sequestered ourselves in our hotel room and read. And read. Avoiding temptations like The Simpsons Movie on HBO, we spent the day awash in Post-Its and highlighters, scribbling notes and occasionally announcing epiphanies.

Some of the articles were especially helpful in getting the lay of the land. Among these were a CLL Topics piece called What Say You Dr. Expert?; an overview by Dr. Andrew Pettitt written for the UK CLL Support Association; and a paper entitled Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus, which reflects the views of European experts (there is no US equivalent). The latter is hard to get hold of but I can send you a PDF if you write to me.

The bottom lines, as near as we could tell, are these (and I would encourage you to find your own hotel and do your own reading and reach your own conclusions):

• Allogeneic transplants are still too risky to undertake without serious thought and thorough investigation. There is a two-thirds or better chance that you’ll get a long term remission or a cure. But it doesn’t take a math genius to realize that there is a fair chance of death or relapse, not to mention the possibility of significantly reduced quality of life due to graft vs. host disease (GVHD).

• Prognostic tests (aka “biological risk factors” or “biomarkers”) alone (FISH, IgVH, ZAP-70, CD38) are insufficient grounds to undertake a transplant, except perhaps in the case of 17p-deleted patients, whose disease is by its very nature resistant to most chemo and likely to be aggressive and result in early death. As the European paper states, “. . . an adverse prognosis suggested by biological risk factors must be substantiated by an unfavorable clinical course.”

• The favorability of your clinical course is generally determined by how well you respond to purine-analogue based therapy (i.e., fludarabine or pentostatin). If you don’t respond well, or if you relapse within two years after combination therapy such as FCR or PCR, you are a good candidate for a transplant. (If you respond to FCR for at least two years, you’ll likely be given FCR again.) A short period (less than 12 months) between diagnosis and the need for treatment is another sign of aggressive disease, though I think it can be argued that since we are all diagnosed at different points in our disease progression, this is something of a moving target.
  
  Dr. Pettitt makes a useful point: “It is very important to remember that the clinical and therapeutic context has a major impact on the prognostic value of some biomarkers. For example the real strength of IgVH gene mutation, CD38 and ZAP70 is in predicting time to progression in newly diagnosed patients with early-stage disease. In patients who have already progressed to the point of requiring treatment, these biomarkers have a relative weak effect on outcome whereas 17p deletion retains its profound adverse prognostic effect. As for patients who are resistant to fludarabine-based regimens, this probably trumps all biomarkers, which therefore become redundant in this setting.”

• The 17p deletion indicates non-functionality of the p53 pathway, in which the 11q deletion is also implicated. The less the p53 pathway functions, the more the body is incapable of killing mangled, mutant cells even with chemotherapy, and therefore the more aggressive the disease. Dr. Terry Hamblin makes the point that “TP53 functional assays might be better than FISH.” Such an assay may be very helpful in further determining whether your CLL is reaching the point of getting out of control. Apparently such an assay is not easy to come by -- welcome to CLL.

• Doctors tend to agree that 17p-deleted patients are better off having a transplant when they achieve their first remission. For the rest of us, they tend to think it should be after the second remission and some might even advise waiting a bit longer, depending upon the patient’s age, general health, prognostics, ability to respond to chemo, duration of remission, and ways in which the disease may be impinging on quality of life.
  
  To see just how unclear the thinking is on this one, the Europeans note: “Although conclusive evidence for CLL is still lacking, experience from other entities suggests that the success rate of the allo-SCT can decrease as the number of pretreatment cytotoxic lines [English translation: chemo regimens] grows. This implies that it might be advisable to consider allo-SCT in eligible patients as soon as criteria for poor-risk CLL are fulfilled. However, the available body of evidence does not allow sound recommendations on this issue.”

• So, in the absence of conclusive evidence, what can we infer from the data we have? Does it make sense to transplant sooner rather than later?
  
  There are two big arguments for not waiting too long. One is that your general health is likely to be better the younger you are, and that means fewer comorbidities and a better chance of successfully undergoing the rigors of transplant. The second argument, and the conventional wisdom, is that CLLers going into transplant with a CR -- which is more likely to be achieved if you have not had too many "pretreatment cytotoxic lines" and become too resistant to drugs -- stand a better chance of success. From what I can tell, this is true. A 2007 study at the Hutch in Seattle showed that none of seven CLLers with a CR relapsed in the first 14 months, while out of 75 CLLers who didn’t have a CR, 31% relapsed.
  
  But that is not the end of the discussion because the risk of death is high enough -- and the success rate of non-CR patients is good enough -- to make waiting a little longer a reasonable course of action for some. It all depends on how you want to play the risk game: transplant sooner and risk not having time you would have had otherwise; transplant later and, having maximized your time already, assume a somewhat greater risk of not having any more of it. This is the crappy craps game you'll have to play.
  
  The European paper has a table that covers seven different studies of patients who underwent transplant. For each study, the percentage of fludarabine-refractory patients is given. I was surprised to see that there were not huge differences in overall survival between studies that had high percentages of fludarabine-refractory folks and those that didn’t. In one study of 73 patients, 82% of whom were fludarabine refractory -- which we can take as a rough guide for how many may have entered transplant without a CR -- the relapse rate was 28% after two years. Indeed, the relapse rate after two years seems to be about 30% in many studies.
  
  Despite the Hutch’s figures on that rather small group of seven patients, there is no guarantee that a CR patient will not relapse. or will not die for some other reason. Having a CR does not protect you from complications and early death (in the first 100 days), which is something around 7%. Nor is it a guarantee against transplant-related mortality, where you might well have a leg up on the non-CR people, but which runs about 15% to 20% in the first two years among all CLLers.
  
  My conclusion is that while a CR is preferable, the desire to attain it does not necessarily trump everything else in making the transplant decision. Statistics are significant from the angle that you look at them. The Hutch study indicates that 69% of non-CR patients had NOT relapsed. The European study shows that after two years 70% out of a heavily-fludarabine-refractory group had not relapsed. My guesstimate is that going into transplant with a CR might add another 10% or 15% to those numbers in your favor. That should not be dismissed, nor should it be seen as the certain difference between life and death. In the end, luck is going to play a crucial role in your outcome.

• For those of us playing softball with CLL by using single-agent Rituxan and the like, it may be hard to define “first” and “second” remission. Most of the experts assume you’ll be using purine-analogue-based combination therapy. How many relapses after Rituxan does it take to equal the “first” or “second” relapse that the experts talk about? All I can suggest is that you look at your ongoing responsiveness to Rituxan, and any additional chemo, as a guide. Eventually, because of AIHA, I needed to graduate to something stronger, the R-C(V)P I had at the end of 2007. I am making an educated guess that my relapse from that regimen will constitute the equivalent of “first” relapse.

• I am making that inference in large part because I seem to respond well to drugs. I always have, be it allergy medication or chemotherapy. The experts agree that disease resistance on the part of CLL will build; the question is at what rate. When there are signs that responsiveness is significantly diminishing, it’s time to think about transplant. Remember Dr. Pettitt’s point about resistance to fludarabine trumping all biomarkers; when the drugs stop working on you, nothing else is going to matter.

• The art of medicine is definitely in play here, as you can tell by reading “What say you, Dr. Expert?” There are the vagaries of the bell curve, the idiosyncratic individual CLL that may give you a break, or maybe not. Ultimately, as I see it, and as I think a lot of the doctors see it, your responsiveness to therapy, your quality of life, and your clinical course and status (e.g, is your marrow still functioning reasonably well?; can you fight off infections?) are the practical factors that outweigh all others. The path to a transplant does not go like clockwork; there is always the need to finesse.
  
  To illustrate that point, here are thoughts from two doctors about the dangers of starting too early and starting too late:
  
  “I had a young patient (50 years old) with unfavorable prognostic factors who was anxious to go to transplant,” Dr. William Wierda of MD Anderson wrote. “He was in CR after his initial treatment. He was transplanted by one of the other transplanters here at MDACC. I was somewhat relieved that he had a sister who was a full match and expected this would reduce his risk for complications. This patient died during transplant, before he had a chance to be discharged from the hospital. I have had many others that have been successfully transplanted, however, this one patient, and the painful conversations I had with his wife after his death, have clearly affected my view of transplant and when to transplant. This is something that I would not like to consider for a 45-year-old with five children.”
  
  Dr. Hamblin points out the dangers of waiting too long: “The thing that stands out for me is that transplanting too late is a disaster. I have seen patients who remain in hospital for over a year after their transplant before they die. They fluctuate between CMV reactivation and GVHD. The treatment for one makes the other one worse. What is common to these patients is that they were transplanted late in their disease.”

• So there is definitely a sweet spot, a best window of opportunity for transplant. Not too early (17p excepted, perhaps) and not too late. While you’re still responsive to therapy, but not while you still have a lot of bullets left. While you’re young and fit enough to cope with the rigors of transplant, but, um, not while you’re young and fit enough to enjoy good quality of life while controlling your CLL with chemotherapy.
  
  To quote Dr. Pettitt again: “At the end of the day, allografting amounts to a big gamble in which short-term risks are traded off against potential long-term gains. The dilemma is not only one of whether or not to have an allograft, but also when to have one. Thus, transplants consistently achieve the best results in patients who have not received too much in the way of previous treatment and are in remission at the time of transplantation. On the other hand, allografting has the potential to shorten as well as prolong life. This is very much an area where there are no clear answers, and under these circumstances patient choice is of paramount importance.”
  
  Which is why I always say: Go with your intuition.

After mulling over these points, Marilyn and I concluded that I was not yet ready to take the leap. While my 11q deletion is not the best of news -- though even 11q is not monolithic, so to speak, and there are better and worse variations that we are only beginning to understand, some of which Dr. John Byrd is testing for at his lab in Columbus -- my better-than-expected response to what was essentially mild chemotherapy was proof that my clinical course was not sufficiently unfavorable, at least not yet, to justify the risk.

Our feelings were validated when we returned home and a new CBC showed that my lymphocyte count was still stable, my red counts had climbed to mid-normal, and best of all I was finally Coombs negative, meaning the AIHA was now less likely to return.

In Part 3, I’ll report on my interview with Dr. Steven Pavletic, transplant protocol chair at the NCI, and his conclusions about my case and insights into the transplant process.

Free at last

I must admit to having cried last night when Barack Obama was elected the 44th president of the United States.

Part of it was jubilation, the sort of feeling prevalent in Eastern Europe back in 1989 when the Berlin Wall came crashing down. As Marilyn said, it feels like we have finally gotten rid of the Ceausescus. That big crowd in front of the White House may as well have been carrying pitchforks.

But the big reason, the one that actually set me to sobbing, was the fact that my country has elected a black man, chosen a leader not for the color of his skin but rather for the content of his character. He will be the head of state, but he will be more than that: like all presidents, he is a symbol of the nation he leads. We do not have a royal family here, but we do have a first family, and they are Barack and Michelle, Sasha and Malia, and a puppy as yet to be named.

Oh, how far we've come.

Racism has always been a part of American life. Our very Constitution established that for census purposes “non-free” residents should count as three-fifths of a person. The Civil War may have ended slavery, but for at least a century afterwards we were enslaved by bigotry. Blacks have been lynched, denied the right to vote, denied educational and economic opportunity, denied the right to ride in the front of the bus. I am not all that old, but I am old enough to remember the events of the 1960s -- the fire hoses, the attack dogs, the murders of Medgar Evers, Martin Luther King Jr. and others -- black and white -- who laid their lives on the line to put an end to this madness.

And then, last night, Americans did something that signified in a profound way that we have changed, that we have become something different, that we have become something better than we were. There was something almost effortless about it, until we remember all the sacrifices it took to get here.

Those racists who were responsible for the Jim Crow laws, for the murders in the middle of the night, are no doubt spinning in their graves right now, working their way ever closer to Hell. Those who are still with us, who just can’t stand the idea of a black man as their leader, as their national symbol, have some waking up to do.

I saw a pickup truck recently with a Confederate flag sticker and the words “Kick Ass White Boy” written above it. Next to it was a big American flag. Well, Kick Ass White Boy just got his ass kicked. And I’ll take those Stars and Stripes back, thank you. They belong to a country that is bigger, grander, wiser, and more diverse than it once ever dreamed it could be.

This is the America I love, the one that shows it is, in ways, the Promised Land. It has not been all that many years since Dr. King spoke on the steps of the Lincoln Memorial. I remember hearing his speech as a kid, and his thrilling words have never rung truer than they do right now:

“And when this happens, when we allow freedom to ring, when we let it ring from every village and every hamlet, from every state and every city, we will be able to speed up that day when all of God's children, black men and white men, Jews and Gentiles, Protestants and Catholics, will be able to join hands and sing in the words of the old Negro spiritual, "Free at last! Free at last! Thank God Almighty, we are free at last!"

The joy of Coombs negativity

Been busy here. Kitchen remodel + Ikea = eating too many Swedish meatballs after tramping around a football-field-sized maze of furniture where everything has names like Akurum, Famtid, and Wurm. Me, Marilyn, and half of Phoenix were there on Sunday. Soylent Green is people!

The good news is that I am healthy enough to endure the experience, which is not unlike a Bataan Death March through a pressboard jungle where gibberish is the lingua franca. My hemoglobin is 14.7, more than double what it was a year ago when I was in the throes of autoimmune hemolytic anemia (AIHA). My RBC is 4.72, hematocrit 41.2. All are well within the normal reference range.

The big cherry on this red blood sundae is that my last two Coombs tests have come up negative, which means the AIHA beast is in its cave, unlikely to show up in the dramatic fashion by which it attacked me last year. Converting to Coombs negativity was my not-so-secret hope when I underwent R+C(V)P therapy for AIHA and CLL, which commenced on October 22, 2007. Conversion took so long to happen that I thought it wasn’t going to. And then on August 19 it did. And on October 7 it did again. (I am a believer in the “make sure you get two tests to confirm a trend” school of blood draw divination.)

According to a study by Dr. Kanti Rai, et al of CLLers with AIHA treated with a similar protocol to mine, conversion to Coombs negativity led to a mean response of 23 months, as opposed to 8.8 months for those who remained Coombs positive. “This finding that Coombs conversion portends a longer duration of response suggests treatment goals for AIHA should be a conversion to Coombs negative, and not stopped with recovery of HGB,” the authors wrote.

Well, I’ll be damned, pass the lingonberries and pour some Absolut in my Ljuvlig, I am one of the lucky ones. I am also lucky in that I achieved this following just three rounds of chemo (not the five or so that most of Rai’s patients had). And that my absolute lymphocyte count is 8.9 a year later, much lower than I ever thought it would stay.

The imperfect part of the picture is that the lymph nodes began to return, slowly, around June and July. This follows the typical pattern of 11q-deleted disease, where the CLL collects in the nodes. They aren’t as bad as they used to be, but they’re there, a definite reminder that CLL relapse after chemotherapy is, like getting a Florvag for your Tolga, inevitable.

Nonetheless, I am for the moment enjoying a satisfying, quiet victory over the most acute medical crisis I have ever faced. My saga is a reminder of how easy it is to take the fundamentals of health for granted, and what a long and difficult slog it can be to return to a simple, functional state.

There are two lessons I am taking away. One is that things don’t always go by the book, that statistics are general but results are individual. By all counts, my response to therapy shouldn’t have been this good. Rai’s patients were Rituxan-naive; I certainly am not, and I had fewer rounds of chemo than they did. Two is that I believe controlling my AIHA is directly proportional to controlling my CLL; when time comes again for treatment I am going to make sure there is at least as much punch to it as there was before. The days of single-agent Rituxan as a means of controlling my CLL are almost assuredly over.

The nice thing about a remission is that I don’t think about these things that much right now. Instead, I ponder what to do with the three extra inches on the wall over the sink, what color granite goes with Adel medium brown, and whether to put a Luftig over the Mumsig.

Had I tried to make it through Ikea this time last year, when my HGB was 6.8, they would have had to carry me out on an Ektorp.

Ibuprofen and AIHA

A few years ago, I read on the ACOR CLL List about a patient who took ibuprofen when his swollen lymph nodes began to bother him. His doctor said it was OK to take 1600 mg daily for a week, which is half the maximum allowable daily dose.

The lure of NSAIDs (non-steroidal-anti-inflammatory drugs) like ibuprofen is their easy availability, low cost, and ability to alleviate symptoms. But like all drugs they come with side effects and toxicities, which means that their role in combating CLL is necessarily limited.

When I read about ibuprofen controlling the nodes, I decided to give it a try. I didn't need a lot of convincing, as I had always rather enjoyed the effects of ibuprofen on those rare occasions when I took it for a headache or muscle pain. It would leave me with a pleasant feeling, not exactly tranquilized, but just that more at peace with the world.

I found that it worked on the nodes to a small and very temporary degree, just enough that I began to take it when my ever-growing nodes got painful. Even then, I never went up to the line and used it as much as I could. I am rather conservative about drug use. The most I did was take it once or twice a day for two or three days.

Later, by the way, when I used steroids, the nodes reduced dramatically, so there really is no contest when it comes to NSAIDs vs. SAIDs. But steroids are much worse in terms of side effects; being conservative about drugs, I used single-agent Rituxan for as long as I could before circumstances, in the form of my AIHA diagnosis last March, forced me to throw steroids into the mix. AIHA, of course, is short for autoimmune hemolytic anemia, about which I have written a great deal, and which I would not wish on my worst enemy.

After I came down with AIHA, I stumbled across an interesting bit of information in the Merck Manual online. Ibuprofen was listed in a table as one of several drugs "that can cause warm antibody [autoimmune] hemolytic anemia."

It was hard to find any more information on the subject, but I immediately quit using it, even on the rarest of occasions. I am convinced, based on my reading and the conventional wisdom of doctors, that my AIHA came about as a result of the CLL having gotten out of control and gumming up the immunity works. But the thought that ibuprofen might have had even a tiny role in helping me reach the tipping point into hemolysis -- the vicious cycle in which the body destroys its own red blood cells -- was enough to make me quit using it.

Some time later, after my R-C(V)P therapy at the end of last year, I wrote to Dr. Clive Zent of the Mayo Clinic. Dr. Zent is a CLL and autoimmune disease expert who has generously allowed me to share his thoughts with you. I asked, quite simply, whether it w as safe to use ibuprofen, or whether it could contribute to a possible relapse of AIHA. Here's his reply:

Ibuprofen -- this is certainly a drug that has been associated with autoimmune complications including AIHA. It (and all the other drugs in its class -- NSAID) have many other potential toxicities which are generally rare. We rarely determine the triggers (if any) of AIHA in an individual. This is all a prelude to saying that unless ibuprofen was the cause of your AIHA, I don't believe that you are at high risk of causing a relapse of your AIHA if you use the drug, but it (and all other drugs) should be used only when indicated. If acetaminophen is effective for your pain, it could be a safer option. 

The bottom line is "better safe than sorry." How to handle CLL and its myriad effects is something that keeps even the experts guessing. Those of you out there who are Coombs positive, or have been diagnosed with AIHA, and who are also scarfing down the ibuprofen, may want to think twice about it.

The sea otter with CLL

Chronic lymphocytic leukemia is not the province of people alone. If you've been around Google a few times you've run into references of CLL in dogs and cats. Indeed, they're pretty much subject to the whole range of leukemias and lymphomas that we humans are. When it comes to CLL, our pets get some of the same treatments that we do. CLL kitties can live a year or two if given chlorambucil. French researchers found that dogs responded to a combination of prednisolone and melphalan (the latter being an older drug that is rarely used in human CLL today).

The animal world has lost its first CLL celebrity, a sea otter named Nyac. She was a 20-year-old survivor of the Exxon Valdez oil spill and a popular resident of the Vancouver Aquarium. Whether or not the oil spill had anything to do with her CLL is unknown, but it didn't seem to interfere with her longevity. Sea otters usually live 10 or 15 years and some have reached 20 in captivity, so she died at a ripe old age.

A statement by the Vancouver Aquarium on Tuesday read in part:

"Nyac was at the upper limit of a female sea otter life span. Over the last 2-3 years Nyac has been showing signs of her advanced age most obviously a gradual slowing down in her general behaviours. In July, Nyac suddenly showed limited energy and mobility. The Aquarium’s veterinary team immediately began their work in an attempt to determine a reason for the sudden deterioration of Nyac’s health. An MRI revealed a serious inner ear infection however blood test results showed a more serious underlying disorder.

"With treatment, Nyac’s behaviour improved and since that time she had been under close observation by the marine mammal and veterinary care teams. Last Friday her condition worsened and she was diagnosed with chronic lymphocytic leukemia.

"Nyac was placed under 24-hour care with key staff in attendance. Her condition continued to worsen until Nyac passed away early this morning.

“Nyac was a very special animal and had been placed under palliative care. Our entire veterinary and marine mammal care team is, of course, devastated this morning. Lymphocytic leukemia has not been previously reported in sea otters and because there is some association with contact with petroleum in other species, she is an important animal. From a medical perspective, Nyac is also very important because of her long life. Even as we’ll miss her we know she’ll continue to provide vital information on the long-term effects of oil exposure.” said Dr. Martin Haulena, Staff Veterinarian, Vancouver Aquarium."

Below is the YouTube video that made her famous. Get out your hankies.

A house of cards

What a mess we’re in. As Chris Dodd put it, we’ve entered an era of privatized profit and socialized debt.

Greed is at the center of it all, greed and lack of meaningful oversight, not just on the part of government regulators but also on the part of corporate elders who should have known better, or should have cared more.

Back in 1984, Marilyn and I bought out first house at a cost of $87,500. It was a definite fixer, an older home with an in-law apartment that had been added downstairs. The couple who owned it were divorcing. She lived upstairs, he was consigned to the dungeon, which he trashed. Termites had built themselves a magical kingdom in the walls. The fireplace was leaning away from the house. Roots from a giant willow tree routinely plugged up the sewer lines. It wasn’t in the best neighborhood. But it was just about the last house in Berkeley, CA for under $100,000 and we were lucky to get it, with 20% down and a 13.25%, 30-year fixed loan.

Jumping through hoops to get financing was expected, and made some sense. The lender needed to know that we could afford to pay the mortgage.

That was back in the good old days, when homes almost everywhere in the country were in reach of people with average incomes. I took a look at zillow.com, just to see how our first home has fared. Riding a real estate boomlet, we sold it in 1989 for $200,000, a record for the block. The boom steadied and the people who bought it from us sold it in 1994 for $235,000.

They’re probably kicking themselves. By 2003, it was worth around $580,000. In mid-05 the old dump reached its peak value, $818,000. Today, it’s $661,500 and heading south.

How can people pay for such huge mortgages? Smoke, mirrors, and lemming-like behavior. Things like 100% financing, or 80/20 financing, interest-only loans, ARMs from Hell, HELOCs, refinancing, issuing loans to the insolvent, paying routine bills with credit cards, which were passed out like candy.

As Suze Orman has repeatedly pointed out, financial management skills should be a required course in high school. Just because someone offers you something you can't afford doesn't mean you have to take it.

This madness started in California, then spread to Nevada, Arizona, Florida and a lot of other places that were considered desirable. I have been to all these places, have lived in two of them, and let me say here that none of them are THAT nice.

Anyone with common sense could see that this could not continue. Our Berkeley hovel more than tripled in value from 1994 to 2005. Were they thinking it would more than triple again, be worth $2.5 million in another ten or eleven years? And who did they think (in their right mind anyway) would buy it at that price?

That we are now in a financial crisis, built on bad mortages, should really come as a surprise to no one. It was almost like everyone, from Wall Street to Main Street, was doing financial crack. Everyone ran on overdrive, pocketing money that wasn’t there.

Now this binge has to be paid for, and we’re all going to suffer. Like most Americans, my visceral reaction to the idea of a $700 billion bailout involves a fair amount of disgust. I don’t like rewarding the avaricious. Especially when this money could be better spent on things like health care, cancer research, and so on.

But I am told that we have no choice. That’s probably the case. We have built ourselves an enormous house of cards, not just in real estate but in credit and investments, things that drive our economy and provide financial security and opportunity. It's a monument to folly that we will be paying for, one way or the other, for a long time to come.

My visit to the NCI, Part 1

Marilyn and I like road trips. We’ve taken them for as long as we’ve had something with four wheels and an engine.

In the old days we went car camping out of our Toyota Celica, pitching a backpacking tent in Death Valley, which threatened to blow away during a dust storm -- with us in it. Then we upgraded to a Volkswagen Westfalia van with a pop-up roof, in which we went over the Rockies in first gear. Our cat, Tut, used to nap on a picnic basket wedged between the two front seats. This was followed by the RV era, which involved towing a house (aka fifth-wheel trailer) behind us. Now we’re back to square one -- just a car -- though we prefer motels to tents these days.

And now that I have chronic lymphocytic leukemia, we’ve combined road tripping with doctor visiting. In 2006, we set out for Columbus, OH, home of Dr. John Byrd. And in July of this year we took off for Bethesda, MD, home of the National Cancer Institute and National Institutes of Health.

We were going because I was looking into a clinical trial that offers free reduced-intensity- conditioning stem cell transplants using matched unrelated donors -- the popular mini-MUD. I need an unrelated donor because I have no sibling donors; my two brothers and one sister are all half-siblings. Since my health insurance won’t cover transplants, participating would be like winning a million-dollar lottery of sorts. Of course, I’d rather win a million dollars and not have CLL, but that’s another story.

CLL Topics published an article about the trial in January, one month after I completed my R-C(V)P therapy for CLL and autoimmune hemolytic anemia (AIHA). The year 2007 had not been kind to me: AIHA was diagnosed in March, treated, and followed by relapses in July and October, each worse than the one before. Not only was my quality of life going down the tubes, it appeared the AIHA might be uncontrollable. The idea of a transplant, which had once been fuzzy and distant, was now taking on some immediacy. It was prudent to look into it seriously, especially as I had no idea in January how long my remission might last.

One in seven million

So I called the transplant coordinator and explained my situation. He said I was, on the face of it, worthy of consideration.

The first step would be to see whether there was a 10/10 HLA match, which is required for participation. (A less-than-optimal match equals less-than-optimal results, both for me and the trial.) A blood kit with two tubes was sent from Bethesda. I had the blood drawn at a local lab and then Fed-Exed the package back to the NCI, along with copies of my medical records.

It took several months to get any answers, partly because the trial was stopped at one point to allow for a routine review of how the protocol was working. It turned out that the six people who had undergone transplants were doing well, and so accrual of patients resumed. A total of 20 people will eventually be enrolled.

The NCI first looked at my blood on low resolution for 6/6 matches, and when a number of those were confirmed by searching worldwide donor databases, moved onto the next step: testing at low resolution for 10/10 matches. Twelve were found, and this was followed by the final search at high resolution, after which the transplant coordinator called with the news: Of the twelve 10/10 low-res matches, only one donor, out of seven million in the databases, appeared to be a 10/10 match at high res.

But one, as he pointed out, is all it takes.

He added that the next step in testing, should I be provisionally accepted into the trial, would be to contact the donor and make sure he or she had no infectious diseases and was physically able to undergo the donation procedure.

The testing and donor searching that had already been done -- which would have cost me $15,000 or more had I been paying for it myself -- thus answered a very important question: Are there donors for me and is an adult stem cell transplant therefore going to be an option now or in the future?

The answer is -- and it’s fortunate that I am not a Type A personality -- “maybe.” It is worth noting here that the 5-million-strong U.S. National Marrow Donor Program database returned 22 low-res 6/6 matches when I used their website's HLA matching gizmo last year. In retrospect, those results are pretty much meaningless. When the rubber meets the road in the form of further testing, 22 6/6 matches can mean bupkus, or close to bupkus. (For those unfamiliar with road trips, Bupkus is just east of WaKeeney, in central Kansas.)

Having completed the HLA preliminaries, the transplant coordinator wanted to move ahead to the next step, an “informational meeting” with one of the doctors involved in the trial. I could have done this by phone, but I hate talking on the phone. You can’t see who you’re dealing with, you don’t have the presence of mind that you do when you’re there with all five senses, and you can’t grok the facility, get an impression of what actually taking such a big step would be like. So off we went.

Did I mention that this was also a good excuse for a road trip?

Meanwhile, back at CBC ranch

In the months following my three rounds of R-C(V)P, my CBC continued to look better and better. Not only had the hemolysis stopped, but my red counts were making a slow climb toward normal. My lymphocyte count was continuing to drift downward. My lymph nodes, which were knocked back to the point of being less swollen than they were at diagnosis in 2003, were stable. By the time we went to Bethesda, my red counts had crossed the line into the low-normal range and my Coombs test, though still positive, was now only “microscopically” so. The nodes had come back a little, but not much. My spleen and liver were behaving themselves. The lymphocyte count had dropped to its lowest level since I had the chemo eight months before.

In other words, I was doing better than I could have hoped when I finished the R-C(V)P in December and approached the NCI in January. And so the transplant immediacy factor was beginning to diminish. When your back is against the wall, you do what you have to do, regardless of the risk. When the pressure is off, you look at things from a different perspective, especially when you are considering taking a step that has a 15% to 20% chance of killing you.

But the prospect of having just one donor added a little drama to my decision as we traveled east. Do I seize the moment before there is no donor at all? Or would it be reasonable to expect that more donors might come along in the future?

And are those even the right issues to be focusing on?

For as a learned friend once told me when I was young and we were all sitting around a campfire drinking a lot of beer, “The thing in life is not to know all the answers but rather to ask the right questions."

In Part 2, I will discuss the questions I asked, the answers I found, and the general consensus to date when experts grapple with the question, "Who should have a transplant when?"


We stopped to see the giant Van Gogh sunflower canvas in Greatland, KS. Apparently Van Gogh was taller than we thought and traveled further afield than is commonly known. The middle photo is of our cat Pyewacket in the driver's seat on our (doctor-visitless) road trip to Nova Scotia in 2004. Both of our cats have enjoyed traveling; we adopted Pye at an RV park. The top photo shows Tut enjoying a claw-scratch at a campground, circa 1987. That's a 1971 VW.

Then and now, Part 2 -- Five years later

Wednesday marked the fifth anniversary of my CLL diagnosis. I am now entering year six of a journey that, according to survival statistics, should last another two to nine years. At which point I will become permanently out of print. Crossed out by the Big Blue Pencil. Remaindered at the bookstore in the sky.

Unless, of course, I get lucky. Which, the statistics show, can also happen.

My feelings about chronic lymphocytic leukemia are a lot different today than they were five years ago. Then, it was a challenge that demanded my full attention: How can I get a grip on the unfathomable to outwit the unthinkable? Now, the adrenaline response to diagnosis is gone. The war of attrition has set in. CLL is less of an imminent threat and more of a lethal annoyance.

This has led me to conclude that, as much as I can, it’s time to get on with my life. In the words of that sage philosopher Doris Day, “Que sera, sera. Whatever will be, will be.”

Over the years I have learned what to expect. I know how the disease progresses, how drug resistance develops, how I respond to therapy, how clinical symptoms have impacted my life. I have seen the pace at which new therapies come along and I know that at the end of my CLL journey, barring something fairly miraculous, there will be a transplant of some kind. And that it will probably either cure me or kill me, and that nothing I do can control the outcome with certainty.

I am along for the ride. Over time I have come to accept my situation, and very little good can be said about it. CLL is a bitch. But I am getting used to it. As the days go by and the crises come and go, it feels less like a roller coaster and more like a bumpy road. And so the experience has taken on a more even feel. It’s not new anymore. It’s just that thing you do, that thing that happens to you.

I used to look for silver linings, and I suppose there have been some. For example, getting to know other people affected by CLL has brought out my empathetic side, made me more comfortable speaking the language of emotion and acknowledging pain and loss. I learned through this blog and online forums that I could turn my experiences into something that might be of help to others. When things have gotten bad for me personally, I have found an inner strength I didn’t know was there, an ability to hold things together and stay focused and not freak out. You could say that I have grown as a person. The shorter my life threatens to become, the fuller it is.

But this is a war of attrition, and that takes something out of you. The silver linings usually pale in comparison to the clouds. There is a slow drain of resources: emotional, financial, and in the form of dreams deferred and plans altered. Five years ago, CLL had an air of unreality about it; now it has been around long enough to have impacted almost everything in my life. It is impossible to deny.

After five years, I have also learned that knowledge is imperfect. For example, in the time since my diagnosis, FISH testing has become part of the diagnostic and prognostic workup. But the test looks for just a few things, and many lay hidden, unseen players in the game. There is a lot that the experts still don’t know about CLL, and the learning curve requires patience; the first chromosomal abnormality (Trisomy 12) was discovered the year I graduated from college, 1979. And in the words of Dr. Terry Hamblin, “We still do not know what it means.”

On a more practical level, I have learned that knowledge can only take you so far. Understanding the tests and treatments and all that is essential. But how your disease progresses, how it reacts to therapy, these do not always follow the rather incomplete book. CLL is notoriously idiosyncratic, and there’s a lot of trial and error when it comes to managing it. There is no way to know for whom the bell curve tolls. And so I have learned to expect the unexpected.

Over time, I have also come to see that knowledge only takes you so far, for reasons that have nothing to do with medicine. The quality of the CLL experience is something that evolves in part from your reaction to it. I am talking about the emotional and spiritual component, what the clouds and their silver linings, the thunder and lightning, does inside of you. There’s who you are going into this and who you become.

In my case, I was afraid of death and am now less afraid. I’m not happy about it, mind you. But I’ve gotten used to the prospect.

I have also found some balance. A CLL diagnosis comes as a shock, and the ongoing experiences of getting test results, visiting doctors, being treated and then relapsing, all these things can create a life lived on a medical treadmill. This was the case with me, and then I realized that when the treadmill slowed, the sun was still rising and shining on a planet that contains more than B lymphocytes. The beauty in life began to reassert itself.

For a time the world is CLL, and then it becomes the world again.

Knowledge only takes you so far. The whispering in your soul takes you the rest of the way. This is where CLL meets the cosmos. Where a terrible burden meets its context. Where the stars float and you do, too, set loose by the unbearable lightness of being.

CLL is nothing more than one possible end to your story.

So keep writing.