Sunday, January 25, 2009

My visit to the NCI, Part 3 - An enlightening meeting

Readers will recall that Marilyn and I took a road trip from Arizona to Maryland last July. Our destination was the National Cancer Institute/National Institutes of Health, where we were to discuss a clinical trial for a matched unrelated donor stem cell transplant. We had contacted the NCI/NIH in January, following completion of my R-C(V)P treatment for CLL and AIHA. I’d had a rough time in 2007; we didn’t know how well the chemo would work, and we were looking at the prospect of moving to transplant sooner rather than later if the chemo didn’t hold. The NCI trial, besides being well designed, had the advantage of being free of charge, and my health insurer specifically forbids stem cell (“bone marrow”) transplants. There was a possibility of a big win-win here, if the time was indeed right and a donor could be found.

As we made our
way from Hagerstown to Bethesda, the last 70 miles on our journey to the NCI/NIH, we had no idea that the question of my participation in the study had already been decided. Marilyn and I had concluded, after a day of reading and reflection while sequestered in our hotel room, that perhaps I might be jumping the gun, all things considered; we were about to find out that, for somewhat different reasons, there would be no trial for me, whether it was needed or not.

The NIH Clinical Center is shoehorned onto a cramped campus
not too far off the Capital Beltway. One is greeted at the entrance by a phalanx of bored security officers who check your ID and your car, rather lackadaisically on the lookout for terrorists. This continues as you enter the parking garage of the Mark O. Hatfield Clinical Research Center, which is part of a 40-acre complex that makes up the largest clinical research hospital in the world. A guard places an orange cone in your path as you head in, checking your visitor passes to again make sure that you are who you say you are.

The Hatfield Center is big and new; navigating through it involves a lot of sign-following and direction-taking. After being set up with an NCI patient number and file -- which was done incorrectly and led to delays -- we were sent to the 12th floor for our meeting with Dr. Steven Pavletic, the protocol chair.

It was pas
t 5 o’clock and Pavletic was running late; the place was practically empty, but had obviously gone through some heavy use earlier in the day. We couldn't help but notice how dirty and unkempt the seating area was. Lunch had happened. Not that this is the bottom line when choosing a transplant facility, but it added to our impression of a big, somewhat impersonal operation. Gone were the legion of senior citizen hospital volunteers we were used to seeing in Arizona, people who straightened the magazines, primped the cushions, and handed out complimentary fruit.

We were finally ushered into a tiny conference room by the transplant coordinator, a uniformed officer of the US Public Health Service. We chose the chairs witho
ut the potato chip remnants and awaited the good doctor.

Steven Zivko Pavletic originally hails from Croatia and is the head of the
Graft-versus-Host and Autoimmunity Unit in the Experimental Transplantation and Immunology Branch at the center. In other words, he knows his way around a transplant and has a specialty in graft vs. host issues. He’s a few years older than me; Pavletic graduated from medical school in Zagreb in 1979, the same year I earned my anthropology degree at UC Santa Cruz. His head of brown hair is starting to gray, he retains a gentle Slavic accent, and he has an easygoing if businesslike manner.

* * *

Our interview b
egan with some questions about how I was doing since my treatment had ended in December. This included a discussion of what lymph nodes can be palpated and a review of my latest CBC, which was about as picture-perfect as my CBCs get, and which elicited an “It’s wonderful!” from the doctor.

Pavletic asked if I had a history of other serious illnesses (no), allergies to m
edications (no), whether I smoked (briefly years ago), had any siblings (three half sibs, which means they may as well be strangers for transplant donor purposes), a history of cancer or leukemia in the family (not that I know of, but my mother was adopted), children (no), and what current medications I was on (2 mg of methylprednisolone plus Nasonex).

We discussed my treatment history, during the course of which I told Pavletic I was Coombs positive -- a sign that I might be prone to AIHA -- at diagnosis in 2003.

“So you never received fludarabine because they were concerned about the Coombs test?” he asked. Single-agent fludarabine has been shown to trigger AIHA in some cases, as many as 23% in one study.

I explained my story: At first we didn’t know my disease was as bad as it is, so we didn’t think we needed to bash it with heavy-duty chemo. We were concerned about fludarabine's T cell suppression leading to squamous cell skin cancers, of which I have a history. Only later, as more prognostic tests became available, did we learn that my biological markers are pretty poor. The positive Coombs had not really been an issue in the beginning -- indeed, my first oncologist had pushed me to use single-agent fludarabine without explaining, or perhaps without knowing, that it might lead to AIHA -- and I had converted to Coombs negativity after using Rituxan.

Pavletic then began what I like to think of as the good news part of our good news/bad news interview (his comments are provided here courtesy of my trusty tape recorder; don’t visit a major medical facility without one):

“The purpose of this visit is to answer your questions. You don’t have siblings so the next choice would be an unrelated donor . . . The preliminary search shows you have a reasonably good chance of a good match. [There will be much more on the donor situation in a later post.]

“You want more than one donor . . . It’s good to have a few choices because it takes a little time to get it set up, and you never know, donors can back out due to medical reasons, private reasons. So we try to have a backup, find two or three so if one falls out we have a backup.

“So I think it’s a reasonable option in your situation. You are relatively young for a transplant, and age is an important prognostic factor for outcomes.”

Here I asked at what point is one too old, or do one’s chances of success become significantly lessened by age.

“It’s linear. Ten years old is better than 35 and 35 is better than 55 and 55 is better than 70. The risk goes up mainly because the risk of Graft vs. Host Disease (GVHD) goes up with age. That’s one of the main complications, although graft vs. host can be beneficial if it’s mild. It is immunologically active against leukemia. A little graft vs. host is good.

“That’s a risk, and then other comorbidities. Right now I don’t see much in your case that you would have other comorbidities -- lung, heart, kidney, liver issues, another autoimmune disease, diabetes, an ongoing infection that’s not under control.” Pavletic said that the echocardiogram and pulmonary function tests that I had been asked to undergo before coming east were both “good.”

* * *

“That doesn’t mean doing a transplant is risk-free,” he went on. “It’s a journey, it’s a process that’s not without certain mort
ality risks, but the whole objective is to eradicate your disease. It’s not recommended unless somebody has enough high-risk features to justify that approach.

“The main prognostic factor is how the disease behaves. Certainly your biological factors, you know, like ZAP-70, are consistent with this more aggressive type, and clinically it’s been demonstrated with the recurrences of disease . . . I think it’s reasonable to consider transplantation.

“We usually recommend, if someone fails one type of therapy and the disease comes back, you sho
uld consider a transplant. Maybe we can still give another cycle of something and see how things go, you know, depends what is the interval between the first and second, but once you fail two attempts for treatment you should consider a transplant.

“In your case, [the possibility of long] life expectancy is still significant, and the likelihood that CLL is going to continue to cause trouble for you in the next year or two is very high.

“You responded well to this cyclophosphamide-based regimen, you are enjoying a good quality of life this last eight months, so you may ask ‘W
hy transplant?’"

I told him about two friends of mine who underwent transplant. One had terrible refractory disease,
couldn’t get anything approaching a CR, but had a 10/10 match and was doing fine almost a year later. The other, PC Venkat, had a double cord blood transplant and did everything right going in but was felled by something unexpected even after he had engrafted.

"I realize there is
an element of chance," I said.

“There are two reasons why people may die after transplant. One is called non-relapse mortality (NRM). It means something bad happens from the complication of the transplant procedure -- stirs up your immune system, immune suppression, toxicities, you can get infections when GVHD, or just from drugs.

“Certainly transplants that are mismatched are a little bit more risky. I would say a cord is more risky than unrelated and unrelated is more risky than sibling, though if you have a 10 out of 10 match that we are looking for, it is fairly close risk to doing a sibling transplant. It certainly inches up in terms of risk, but it’s not dramatically different . . . I w
ould say maybe the risk of GVHD, the risk of infection is certainly somewhat higher.

“Non-relapse mortality goes up with organ dysfunction and comorbidities, the performance status -- all these things are pretty good in your case. How good is the donor match. Age as well plays some rol
e. With the regimens we use these days, I would say NRM is between 10% and 15%, depends on the situation.

“Nobody has a crystal ball. What works for one person, if you survive and do well, then 1% is good. Ballpark, looking at your whole features, I would say from doing the procedure there should be a risk of somewhere between 15 and 20% of mortality within two years after procedure from some complication. That would be on the higher end, but I would say the risk is real.

* * *

“The other risk of mortality is from disease progression -- if somebody has refractory disease that’s not in remission, it’s certainly more likely to come back or not go away than if somebody has a chemo-sensitive disease and remission. As you do clearly have a chemo sensitive disease, that improves the odds of staying in remission.

“This is why we do transplants in CLL. We tend to say that it’s an uncurable disease by chemotherapy. It tends to come back.”

Pavletic used his hands to mimic a survival chart.

“This is like 5 years, 10 years, we have those survival curves maybe you have seen. If disease is more aggressive, if someone is diagnosed with disease of your features, I would say the data show the survival is somewhere like seven years. With each subse
quent treatment, the disease gets more aggressive, so -- I will make it up -- but your anticipated survival curve is maybe here, two years or something.”

I made a mental note to self: Two years seems awfully pessimistic given my situation -- Dr. Terry Hamblin has pegged survival for patients of my unmutated, 11q-ilk at between 8 and 15 years -- but the general point is well-taken.

“So a transplant kind of fits. You can get all these complications and you can potentially die during the initial phases and then it tends to kind of plateau like this [more hands] where I can’t project exactly, but I would say somebody like you has somewhere around a 70% chance o
f long-term, disease-free survival. That would be a conservative estimate. These other 30% going to --"

"Relapse or die," I interjected.


“And then you get this immunotherapy portion where we really are with CLL in transplants. You know, we get rid of the disease, but it comes back . . . It can come back, late relapses have been described occasionally, but most of this stuff happens the first years. It doesn’t mean somebody can’t relapse at seven years or fourteen years.

“The other risks of transplant besides the mortality include chronic graft vs. host disease. It could be some interrupted quality of life or disability. Some people can control this, get off all the immuno
suppression we give, but there could be some residual damage from GVHD to lungs or some other organs that can be a little bit impaired. But most of the time people can get back to normal function -- I would say in 80 to 90% of cases.

“Late effects
are cataracts, second cancers like squamous cancers, the risks go slightly up. They have to be watched for.”

Since we were on the subject, I went through a list of questions I had brought and got some interesting answers:

If someone has a history of squamous cell cancers and a tendency to rashes -- can you extrapolate from this that after transplant they may be more likely to have a graft vs. host skin condition?

“No, no. You still have to watch for skin cancers. That does increase slightly, even for people who have had no skin cancers.”

I had mononucleosis as a kid and still have the Epstein-Barr virus running around in my system. What does that imply?

“Certainly compared to situations where both you and the donor would be negative for that sort of thing, you have potential for reacting the EB virus somewhere during the transplant, but it rarely has major implications. Rarely people can develop what we call post-transplant lymphomas that can be life threatening but usually not in this kind of transplant that you would get; usually that happens in T cell-depleted transplants. Most people are positive for EBV, so it is hard to find a situation where someone is negative.”

Splenectomy is used for refractory AIHA. Would I be shooting myself in the foot, transplant-wise, by having one?

“Not really. Having no spleen theoretically makes patients in the general population a little bit more susceptible to certain bacterial infections. But in transplant the immune system is compromised already, we would do all the necessary prophylaxis, so I
would say there’s no major impact on transplant.”

If I have a successful transplant, might I be rid of the AIHA as well as the CLL?

“We don’t ever say 'never' here, but once you get a good engraftment, it would be highly unlikely to have a flare-up of AIHA.”

Pavletic began to sum up:

“So the options in your case: We can say 'Let’s see how long it goes,' maybe re-treat, some other things. Hemolytic anemia -- you never know when it’s going to hit; it could be life threatening -- rarely -- but it is certainly something that complicates this whole picture.

“My point is, you are a good transplant candidate. I think it’s a good c
onsideration. There are reasonably good choices of donors. It’s not without risk. It’s not that you need to rush for a transplant tomorrow; you can see how long it goes. I think some other drug combinations or something can again put you into remission. But it’s your personal decision. You shouldn’t feel being pressed into this. If it’s something you are considering, you’re never going to be at a better point for transplant than you are now, because later the disease may be more refractory, you may get some other medical problems. But it’s not a situation when you have to jump tomorrow, but it is a consideration that is very fair.”

* * *

And then the other shoe began to drop.

“Now, speaking of what we can do here, I have one concern that’s quite serious, because we have only one program and that protocol includes fludarabine, not only for conditioning but for preparing -- the way our protocol is written -- to get you to that conditi
oning for transplant. If your immune system is not suppressed enough, measuring by lymphocyte count, we give between one and three cycles of chemotherapy called EPOCH-FR [etoposide, prednisone, vincristine, cyclophosphamide, and adriamyacin plus fludarabine and rituximab]. We have found that it improves, accelerates the engraftment. And you get another dose of FC for conditioning, which means chemotherapy that is supposed to finally prepare your immune system. That’s how we do it here, and we don’t have wiggle room changing that protocol."

I made my pitch. I explained that I’m OK with fludarabine if I’m not actively hemolyzing and if the risks are worth the reward. I described data from MD Anderson showing that when used in combination with cyclophosphamide and Rituxan, both of which act against AIHA, the effects of fludarabine appear to be mitigated and AIHA is triggered no more than usual.

Pavletic didn't appear to be impressed by the MD Anderson study.

“I don’t think anybody would give fludarabine as part of FCR to somebody with active hemolytic anemia --"

You’d be surprised, I told him, and there was a fair amount of laughter in the room.

“It may be a consideration if that’s the only option for somebody. Yes, as you say, some people give it or some people don’t even give it with a positive Coombs test and some people, they think it’s nonsense not to give it -- so there’s a little spectrum of opinions there.

“I would personally say, if you have to give it, then give it, but if you don’t have to give it, do something else . . .

“Sometimes hemolysis can be very violent, and nobody can say if it’s going to be mild, moderate, or severe.

“I think your disease is, so far as I understand here, at a good point. I don’t feel like you need anything right now. Maybe I’m wrong on that, but it sounds like you had a good response to your treatment. Maybe they can give you a few more of this CP-Rs. It would probably have a beneficial effect again. I’m not seeing anywhere now written on the wall that
you must get fludarabine for any purpose. There’s still wiggle room around that.

“Speaking of our protocol, there are conditioning regimens and there are protocols that don’t use fludarabine. Not too many choices -- fludarabine is very popular as part of conditioning regimens -- but there are options like using total body irradiation in middle-of-the-road doses.

“So if you do a transplant here you are taking a risk, biting the bullet. There are cases we’ve done in transplant situations where nothing bad happens, and there are cases where something bad did happen. But we have this extra layer, we’re asking for more fludarabine before the transplant.

“My bottom line, what I’m saying, is it would not be a good choice to go for this study if you can find one that has no fludarabine in the conditioning. It’s just taking unnecessary risks for us and for you.

“This is a very specific protocol that may not be acceptable either to you or the study to expose you to those risks where we don’t know how it’s going to pan out. If you ask my gut feeling, there’s probably at least a 50% chance you would go through this and have no problem relating to hemolytic anemia, but why take another 50% chance or risk or 30% or 20% that something may go wrong and you say, 'Oh, my god, why did we do that?’

“Why take a 10% risk if you can not take a 10% risk? You have other headaches with a transplant.”

* * *

Pavletic suggested visiting other transplant centers where the induction and conditioning regimens would be more flexible. Much as I was disappointed in being rejected for the NCI study -- it would have been nice to have the option, if I decided I wanted it -- both Marilyn and I agreed that in an ideal world, Pavletic was right. Our plans to get better health insurance, which include moving to a state that has an insurance pool for high-risk patients that will cover a transplant, began to look more like a necessity and less like a

The doctor spoke a little more about where my case stood and what I need to consider:

“It’s your decision entirely. Do you want to move on [to transplant] or not? I think everybody would agree that it would be reasonable to move on. Nobody has a crystal ball saying how your CLL is going to behave, and you have to understand that if you say ‘I’m going to sit and wait,’ you may have some disease progression that is going to make it hard to get in remission for transplant.

“There are no great options, but maybe the same thing [R-CP] would work, maybe high-dose chlorambucil, maybe Campath, maybe investigational drugs. These sort of things could buy another inch of time, maybe a year without symptoms, maybe six months, it’s hard to say. But the more subsequent relapses you get, certainly the likelihood of transplant being effective, it’s going down. And nobody with age gets younger and healthier.

“So I think you have some wiggle room. Go around, think it out, work on
your life issues, go some other places and get a consult, stuff like that. It’s not a state of panic, but I would encourage not getting complacent.”

* * *

And so, here I am, in January 2009 having relapsed at last, not getting complacent.

There is another little NCI piece of the puzzle that merits its own post, in which I finally learned in detail what my chances really are of finding a 10/10 donor match. That will be coming soon to a blog near you.

It will, along with recent CT and FISH results and my responsiveness to just-completed R-CD therapy, shed some light on my long-term strategy. I am reviewing that now, given all that I have learned since our visit to the NCI in July. A post summarizing that, and the options as I see them, will eventually follow.

In the meantime, those keeping score will be happy to hear that my one round of R-CD has turned the corner on my hemolysis. Red counts are heading back up, my dexamethasone dose has been reduced to 2 mg a day, I've lost more weight -- another lymph node baby -- and the lymphocyte count is heading down.

It will hold me -- for now.


I received a call in August from the transplant coordinator with Dr. Pavletic's official recommendation: Enjoy my remission and then use FCR if the disease progresses, which is an interesting turn in his thinking given his objections to giving me fludarabine. FCR would then make me a candidate for a transplant. Relapse after fludarabine therapy is a common step on the way to transplant; must I prove my bona fides at some point by having fludarabine and relapsing? Or is there another path?

Thursday, January 15, 2009

Bernie Madoff screws leukemia patient

That would be me. I have been debating whether to write about this. I try to stick to chronic lymphocytic leukemia in my posts and up to now my financial situation has not been especially germane. But I have just lost my savings, and it is important to remember that not every aspect of the disease is medical.

Cancer changes lives in many ways. It refocuses energies -- mental, emotional, spiritual, financial. It transforms everything, from the mystical to the mundane. That mundane world includes money. Cancer can change your career, deplete your bank account, eat you out of house and home even as it eats away at your body.

Bernie Madoff, like a metastasizing financial tumor, has not helped matters of late.

Madoff is the former NASDAQ chairman whose Bernard L. Madoff Investment Securities LLC stole some $50 billion in history’s largest Ponzi scheme. I lost $65,000. That may not sound like much to Madoff, or perhaps even to you, but it meant a lot to me.

Ironically, when it comes to leukemia and lymphoma, I have something in common with the Madoff family. Madoff’s nephew Roger died of acute myelogenous leukemia in 2006 at the age of 32, shortly after he wrote a book called Leukemia for Chickens. His son Andrew was diagnosed with mantle cell lymphoma in 2003, which prompted Bernie to donate millions of dollars to the Lymphoma Research Foundation. My official diagnosis is CLL/SLL: chronic lymphocytic leukemia/small lymphatic lymphoma. In my more poetic moments I like to think that perhaps Bernie donated my money to efforts to beat our common beast.

Probably not.

* * *

Madoff and my family go way, way back. His wife, Ruth, went to high sc
hool with my stepmother, Cynthia, who is quoted in today's New York Times. (Cynthia is like a real mom, and is a good friend, and I love her dearly -- even when she beats me at Scrabble.) Cynthia's parents owned a small, rustic summer resort in New York's Catskill Mountains called Sunny Oaks; during the winter they lived in the same Brooklyn neighborhood as Ruth’s parents, Sol and Sarah Alpern, with whom they became friends.

The Alperns were regular guests at our hotel for two decades, arriving after Memorial Day each year and staying until Labor Day. When I was in college I waited on their table. Later, my Dad and Cynthia inherited the hotel, including the Alperns, and eventually Marilyn and I helped manage the family business and we became hosts to the Alperns. (Sunny Oaks finally closed in 1999, a relic of a Borscht Belt era that had long since passed. The Alperns had passed away by then, too.)

Sol and Sarah were easy guests. They never complained, and although they took one of the best rooms in the h
ouse, they weren’t fancy people. This wasn’t a four-star place. It was basically a collection of rickety old wooden bungalows that we dubbed “cottages,” and it was, as they say in Yiddish, haimish: homelike, friendly, folksy. The guests were treated like an extended family. And we took good care of the Alperns, even when Sarah got old and started to pee on cushions in the lounge. We’d mutter something like “Sarah Alpern is going senile” and just turn the cushions over. (This sort of thing explains why Fawlty Towers is my all-time favorite TV program, but I digress.)

It was Bernie Madoff who eventually gave us all the golden shower. But for the longest time, he was a distant acquaintance who professed nothing but gratitude for the way we took care of his in-laws. Sol, by the way, was an accountant. He knew people on Wall Street, certainly through Madoff and his circle, and he was instrumental in spreading the word at the hotel when good business opportunities came along.

Which, to make a long story short, is how we all
ended up with accounts in Madoff. My history with it goes back almost 20 years. Nobody ever questioned its legitimacy. (It probably was legitimate in the beginning; Madoff was a pioneer in electronic trading back when MS-DOS was the world's most popular operating system.) Statements from Madoff came promptly and looked proper, providing endless lists of transactions. When Marilyn added it all up at tax time, it seemed entirely believable. We often got an annual return of about 10 percent or so, which actually declined in recent years.

Our theory about that decline was that ours was
something of a nuisance account. We kept removing principal and were small financial potatoes, not worth any special effort on the part of the traders (or what we thought were the traders). Indeed, we were allowed to start our account with $50,000. This was in the early days -- a favor -- before Bernie decided you needed two million bucks to get in.

Way back when, our little hotel turned out to be fertile ground for investors for Bernie. Almost everyone in the family had a Madoff account. Accounts radiated out through the guest population, through our distant relatives and the distant relatives of guests. All told, I can think of a dozen people I know who are, collectively, out at least $5 million, and I am sure those people know another dozen people.

I was financially irresponsible, unlike a number of folks
who let their money sit in Madoff and grow and grow. It turns out that irresponsibility has its rewards because at least I got to spend most of my money. I know people -- not rich to begin with -- who are essentially broke.

We’re not talking about the P
alm Beach set that has grabbed much of the media’s attention. This is the Brooklyn-Far Rockaway-where-Madoff-grew-up set, the middle-class-people-who-worked-hard-and-saved set. I know people who lost in the hundreds of thousands, whose money represented their life’s work as well as inheritances from their parents. Some have careers or good equity in their homes or are old enough to be receiving social security or a pension. Others have less.

One cousin wrote that when her checking accou
nt is depleted in February, “I have nothing.”

* * *

I almost closed my Madoff account earlier this year. (Talk about a “D’oh” Homer Simpson kick- yourself moment.) The return was so small -- around 4 percent -- that I was tempted to find another place to put it. But the idea that the money wasn’t safe never crossed my mind. Nobody expects to be a victim of the world’s larges
t Ponzi scheme, especially after so many years, and especially by a man who was both a family friend and a respected Wall Streeter who had actually been hired as a consultant by the Securities and Exchange Commission at one point.

And inertia is a powerful force. “Madoff” was synonymous with “bank” in our circle. It was like “Kleenex” for "tissue" or “Xerox” for "photocopy
." “I’ll put the money in Madoff.” “I’ll take it out of Madoff.” Gifts, trips, cars, down payments on houses, all came from “Madoff.”

Especially in recent
years, when leukemia took a toll on my ability to work and required expensive visits to doctors, “taking another $10,000 out of Madoff” became a yearly event. In the end, I had $65,000 invested -- most of it in my father's account, which was earning a higher return. That money was there as a cushion, to be used in case I needed a transplant or other invasive therapy, in case Marilyn couldn’t work because she needed to spend several months taking care of me. (I was also secure in the knowledge that my folks -- who ultimately lost all their liquid assets to Madoff -- could lend us a financial hand if we really had our backs to the wall.)

And Madoff maintained h
is distant but cordial relationship with our family. As described in the Times article, Cynthia saw Bernie and Ruth at her 50th high school reunion in November 2007. Madoff gave her a big hug. This fall, when the market was showing signs of serious decline, Madoff assured a friend of ours that there was no cause to worry, that in September he had put everything into treasury bills.

Then, on December 11, I got a call unusually late i
n the evening. Cynthia was on the line and I asked her how she was.

“Not too good,” she said morosely. From her tone, I took it that someone had died, or been injured, or was diagnosed with a serious illness. I know all too well how such things can come out of left field.

What she told me was even more unexpected, that Madoff had been arrested and that we all had apparently “lost everything.”

In the ensuing weeks, we have been busy keeping up on the legal issues involved. It appears that eventually -- largely thanks to SIPC, the Securities Investor Protection Corporation -- some of us will see some of the money back. But it could take years, and most of us will never come close to recovering completely from the loss.

* * *

The Madoff mess has taken a toll on its victims i
n different ways. There is the obvious shock, the feeling of betrayal, the loss of security, the anger and the depression. I have been through all that, but I also have a potentially fatal leukemia and that means I have a somewhat different perspective.

Over the past few years I have lost many friends to disease. Seven months ago I lost an especially dear one, my buddy in the battle. I feel my own body struggling as the CLL progresses. I know that I may well be living my life in dog years, four years for every one. I have had to deal with the prospect of the loss of everything, and so I have become an expert on loss. I have a big picture way of looking at i

Madoff hurts, it is a horrible inconvenience, but it will not transform my life the way it will for many others. This is because leukemia has already taught me what E. M. Forster once wrote, namely that "We must be willing to let go of the life we have planned so as to have the life that is waiting for us."

I have already had my life changed, redefined, redirected by events out of my control. For many Madoff stakeholders, this is a new and frig
htening experience. For me, it’s “been there, done that.”

I did not choose to be fighting a deadly, chronic disease in my late 40s and early 50s. It upset my assumptions, put an end to dreams. But it is the life I have, and the struggle has taught me some interesting lessons. There are lessons that money and status and ambition can never teach you, things that come in quiet moments when you face the reality of life and death.

The lessons are these:

It’s not what you do for a living, it’s who you are as a human being.

It’s not what you have, it’s who you have.

I have my soul-mate, a woman who will happily live with me in an old trailer on the edge of the desert so long as we can still be toget
her. We discussed this long before Madoff collapsed, knowing that chronic disease + medical bills + self employment = a recipe for poverty.

From Marilyn (and family and friends) I have endless love in my life, and I would not trade that life -- cancer included -- for all of Madoff’s billions. And so, even in the starkest moments of financial despair, I still regard myself as the richest man in the world.

That is the perspective I keep coming back to, though sometimes it takes awhile after I hear new stories of the pain Madoff has inflicted
on others, or I see his smirking face on TV as he walks back from the courthouse to his penthouse.

The media likes to say that Bernie Madoff, financial psychopath, “destroyed lives.” He certainly disrupted lives, created misery in lives, brought great heartache. I take none of that away from anyone.

But my message to the world is that he destroyed money, not lives.

Believe me, there is a

Five years after our hotel closed, this was Sol and Sarah Alpern's room, right before demolition. There's something symbolic about the wreckage, in restrospect. It sums op our family's Alpern/Madoff experience.


Yours truly was interviewed for this Jan. 29 Bloomberg news report, which is mostly accurate, though Madoff was never a guest at our hotel. He and Ruth visited the Alperns a few times just for the day.

Wednesday, January 14, 2009

There but for the grace of God

I am reminded, whenever I am in the chemo room -- as I was Monday -- that there are worse things to have than chronic lymphocytic leukemia.

A man, three years older than me, in a wheelchair . . . Had a massive heart attack in 2001, died and was revived, six months of memory loss that led him to wonder why he had scars on his chest. Two more heart attacks.

He has myelodysplastic syndrome -- unable to create sufficient cells in the marrow. He lives on transfusions, goes in when the platelets get to 13. After getting red cells, he enjoys a hemoglobin of 10 for a few days until it starts dropping like a rock again.

He also has rectal cancer, spent six months with a colostomy bag, and is now refractory to the original treatment. Trying something new, hoping it works.

His wife runs their business, has learned the caretaker's art, deserves an honorary RN at this point. Jokes that they call him "la cucaracha" because he, like cockroaches that would manage to navigate the end of the world, is a survivor.

He makes jokes about "asshole doctors," manages some smiles. He's rooting for the Cardinals (this is Arizona). Life goes on.

Saturday, January 10, 2009

Dave's doing drugs

Among the skills I have picked up in the strange alternate universe of CLL -- I think many of us have earned a Junior Hematologist badge, for example -- is Armchair Urologist, or Parser of Piss.

I'm not sure which title I like better. It all depends on how the medal will look on my CLL Cadet uniform. I am providing a graphic of the hematology badge here, but obviously more work needs to be done on the concept, including a helmet to protect us from small children with hacking coughs.

However, I digress.

Readers may recall that hemolysis, the process by which autoimmune hemolytic anemia destroys red blood cells, can turn urine orange. This is because the red cells are red and their dead hulks combine with urine's natural yellow to make, as we all learned in first grade, orange. Several times during 2007 -- my annus horribilus of hemolysis -- I was alerted to sudden ill-fortune by the color of my urine.

On Wednesday it happened again. What floated in the toilet that evening was just too dark, too burnt, too damned orange. By Thursday morning there was no doubt about the consistency of the color. This wasn't a one-time thing; it couldn't be blamed on the contrast I had to drink for my CT scan Wednesday morning. Things had definitely changed for the worse. Marilyn verified my suspicions (oh, the wonderful stuff CLL couples get to share). I am sparing you photographic examples, dear readers, despite the age of the cheap and easy digital camera.

Since I had enough hemoglobin in reserve -- it was measured at 12.1 on Monday -- I did not hear the pounding in my ears that often comes when I am hemolyzing and the re
d cells are quickly declining. Which just goes to show that you need to multitask when looking for symptoms of hemolysis. Besides listening for pounding and examining urine, I would recommend being aware of subtle changes to your physical stamina -- for example, did you get more winded walking up the steps today than you did yesterday?

(Since we're discussing the art of hemolysis divination, this may be a useful aside: Although my hemoglobin was h
igher on Christmas Eve eve when I did hear the pounding, I had also had a lot of brandy and egg nog that night -- ho, ho, ho! -- and my theory is that the alcohol in my blood may have facilitated a thinning or enhanced an echoing that I might not have otherwise heard. This is yet another reason why getting drunk periodically is very important for those in my situation.)

* * *

Meanwhile, back at Orange Elimination Ranch . . . A phone chat with Dr. Belle on Thursday led to doubling my dose of Decadron (dexamethasone) to 8 mg daily, as well as to a stat CBC Friday morning. Sure enough, my HGB had dropped to 10.9 in just a few days; my overall red count went from 3.48 to 3.05.

The good news is that the higher dose of Decadron turned my urine a lovely pale yellow again, something that would probably be named "whispering sunrise" in the Ralph Lauren paint section (what have we come to?) at Home Depot.

But I know all too well that it won't hold me for long. So I will be arriving bright and early Monday at Dr. Belle's o
ffice for some chemotherapy, which I prefer to think of as my Day of Hematological Beauty.

We're doing a round of RCD -- Rituxan plus cyclophosphamide plus dexamethasone -- the protocol advanced by Kanti Rai and his group to combat CLL and AIHA (as well as ITP). This is quite similar t
o what I had three rounds of starting in October 2007, just without the one baby dose of vincristine and with dex instead of methylprednisolone. Hopefully that will nail the AIHA like it did in the past (all the relapsed patients in Rai's study responded when treated with RCD again).

We'll be doing a second act, of course, and maybe a third. We may do more rounds of RCD, we will explore some other ideas, and I'm sure we'll go over the CT scan to determine how hard we feel we need to hit the disease.

The fact is that I can't rely forever on RCD or a variant to get me through the CLL-AIHA double whammy.
I need to consider sterner measures that don't also have the effect of shooting myself in the foot, or at least not blowing the whole foot off. (I'm thinking that cadet uniform needs some lead boots.) Whether this means going with a traditional approach or something more experimental, only time, education, and discussion with my doctor will tell.

* * *

Meanwhile, I'll try to fit in a little rest on chemo Monday. I plan to bring a good book, The Pirate Hunter: The True Story of Captain Kidd, an entertaining read about privateers and pirates at the turn of the 18th century. This is what probably started me thinking in terms of costumes for CLLers.

That, and my natural tendency toward eccentricity, which is only enhanced by the Decadron's powerful side effects. It should be said here that having had both dex and methylprednisolone (Medrol), I can see a definite difference in the mental as well as physical effects of the 'roids. Medrol made me just a tad worried about things. I remember staring into the mirror one night and wondering if my gums were receding. Dex puts me more into overdrive, in a positive and focused way. I'm getting less sleep, but, hey, have you noticed that there are a lot more posts to this blog of late?

Speaking of which, I am promising you an interesting post next week about something else that has happened in my life, torn from today's headlines. It tuns
out that yours truly sort of knows someone famous, or that would probably be "infamous." A modern-day pirate, matey.

Aaaarrrghh! And I do mean aaaarrrghh (as opposed to aaaarrr), with all the frustration the word entails. Stay tuned.

Tuesday, January 06, 2009

I’m a lymph node baby daddy

OK, I’ll sheepishly admit that if it’s late at night and I can’t sleep, I’ll watch the Maury Povich show. It’s more mindless than medication and a lot less expensive.

Maury, for those of you who have your TVs tuned to PBS, is a long-running talk show host whose specialty is DNA paternity testing. If there’s a woman in America who slept with 20 men two years ago and can’t figure out who the father of adorable little Brandy is, Maury will keep testing until he finds out.

Like a Kabuki dance or the Oberammagau Passion Play, each Maury set pie
ce opens with a predictable series of events, usually involving a couple and a lot of bleeped cursing and protestations of the "I'm not your baby daddy!" variety. There are two possible outcomes after Maury rips open the envelope with the test results: One is to shout “You ARE the father!,” which usually leads to a crestfallen look on the part of a young gentleman. Alternately, Maury will shout “You are NOT the father!,” which will cause the man to do a little victory jig while the woman runs screaming from the stage.

Well, no special testing required, I am he
re to report that I am a lymph node baby daddy. When I began 4 mg of Decadron (dexamethasone) to control my autoimmune hemolytic anemia on Christmas Eve, I weighed 212 pounds. A week later I was down to 202. My neck was noticeably thinner, as was my abdomen. I had lost my pregnant look.

I discussed this with my doctor, Dr. Belle, during an office visit on New Year’s Eve. (In case you hadn't notice
d by now, I like to mark every holiday with a special medical event.) It is common for people to gain weight on steroids but not to lose it, she said. Not unless there is a whole lot of CLL and attendant nonsense sloshing around in the body’s 600 or so lymph nodes.

This happened to me before, in March 2007, when I first took steroids to combat the initial attack of hemolysis that led to my diagnosis with AIHA. I was on 72 mg of methylprednisolone daily then (4 mg of Decadron is worth about 21 mg of MP) and lost 20 pounds in nine days. I was bulkier to start with and was doing Rituxan at the same time, which had a synergistic effect when it comes to cell kill. In both cases I spent the first couple of nights peeing like a horse.

* * *

My weight loss has slo
wed for now, and despite the joy of effortlessly losing ten pounds, the whole episode raises some serious questions that have bearing on my next steps in terms of therapy.

One, for example, is just how pregnant with lymph nodes am I? Do I have twins in there? Triplets? (The average baby weighs six to nine pounds at birth, so I appear to be working on a second one.)

All the usual blood-based monitoring tools -- lymphocyte count, hemoglobin, platelets, annual FISH -- give us a
glimpse into the state of our disease. But especially in “bulky”or “SLL-ey” or 11q CLL patients like me -- 11q clones love to collect in the nodes -- these tests can show us just the tip of the iceberg.

It wasn’t the visible part of the berg that sunk the Titanic, after all, and more
than one CLLer has awakened from testing complacency to find something going haywire fast. Count me as one of them. I was Coombs negative in November, resting on my RBC laurels. By Christmas Eve I was hemolyzing again. The Coombs was positive, reticulocytes were high, and haptoglobin was low. It was the pattern of 2007 repeating itself again.

During the year’s remission that I enjoyed following the completion of R-C(V)P therapy in December 2007, the disease began to return, creating the conditions of immune dysfunction that led to hemolysis again. I could see the lymph nodes in my neck slowly coming back. This was no surprise -- It’s a chronic disease, after all. That I was lulled into thinking all was well by looking at the numbers -- well, that was shortsighted.

* * *

A word is in order here about lulling. I had a very rough year in 2007. So when 2008 dawned with a pencil-thin neck, low lymphocyte count, and red cells on the rebound, I was prepared to embrace the good news. Despite my trip to the NCI to discuss a stem c
ell transplant trial, I made an effort to spend as much time as possible not thinking and worrying about CLL. Managing this disease can lead to burnout, a depletion almost as profound in its own way as the effects of leukemia upon the immune system. It did not help that I lost more friends to the disease, including a particularly good one.

And so I took a bre
ak, which gave my ever-loving and giving caregiver a break, too. I didn't look for clues. I figured no news was good news, and when I got good news on a test -- and I kept getting such news into November -- I embraced it. I knew the nodes were growing and I knew I would have to be back in this fight again, so I cherished and jealously guarded the time that I was, as they say in the military, on leave.

In the end, worrying all year probably would have made little difference to the outcome. I don't blame myself for taking some down time, especially as I was ready by dint of past experience and knowledge to jump into action immediately when needed, and especially as I have a doctor who is really and truly there when I need her. Those factors made me a little more comfortable turning my back on CLL for awhile, which means that I didn't flirt -- too much -- with danger.

* * *

In CLL, many things go on where the sun don’t shine, and this especially includes the
peritoneal (abdomonal) cavity. God knows how many more lymph node babies I have in there, gumming up the works and growing into masses that not even Decadron can flush away. It can be notoriously hard to feel these nodes, or any large abdominal mass. Marilyn once had an ovarian cyst the size of a cantaloupe that she couldn’t feel until it twisted on its axis and started to abscess.

Doctors will tell you that, especially as time goes on, CLL can change in the way it behaves and the locations it chooses to hide out in. When docs refer to "the natural history of CLL," they mean the course it takes, which can in many ways be affected by the treatment we throw at it as well as the clonal evolution of the disease itself. (Clonal evolution is what happens as more bad copies of CLL cells are made, giving rise to new groups of clones with particular properties. For example, I began my CLL career without 11q and later developed it.)

One's CLL may go from being more leukemic -- present in the blood -- to congregating where it is safest from therapy, namely the deep abdominal nodes. There is a reason this is the location where Richter’s Transfor
mation to lymphoma occurs. Not that I’m worried about that at the moment, but a constellation of such nodes provides the breeding ground for that sort of thing if sufficient T cell suppression occurs. At the very least, hidden interior bulk may be keeping my immune system so dysfunctional that the AIHA can never be put somewhat confidently to rest.

* * *

So, what to do? Well, aside from Philippine psychic surgery, there’s the CT scan, and that is what Dr. Belle and Marilyn and I have agreed to do to help us d
evelop a treatment plan. The last time I had a thorough one was at diagnosis in 2003. I'm going in tomorrow for another.

I know there are those with reservations about radiation, but the prudent use of X-Ray technology can answer some important questions. Here I am, with 11q CLL, prone to bulkiness, having lost enormous lymph node weight, having relaps
ed rather suddenly. "Don't worry about what you can't see" is a rather hollow option, even though this is often repeated to us patients, sometimes by doctors. Power, such as we have it over this disease, comes from knowledge. The Titanic had a watchman who saw the iceberg in advance, just not soon enough to avoid the damage. (For a reasoned opinion on the use of CT scans and other imaging in CLL, read Dr. Terry Hamblin's blog post entitled CT Scans.)

To develop a strategy without knowing as much as I can about the enemy is wasted effort. To do treatment and say that it’s a success because all the peripheral blood numbers look fine is also folly.

We need to see as complete a picture as possible going in. Once we have that picture, we’ll have a better idea of know how to proceed. In the meantime, the steroids are holding me, just barely. My hemoglobin has been stable, at 12.1, for the last week. I feel pretty good, despite the Decadron, which gives me a wired effect that tends to make me want to dance like one of those relieved guests on Maury.

Thursday, January 01, 2009

The new adventures of old vincristine

And no, I won’t be having any more of that drug again.

Readers may recall that my doctor and I settled on R-CVP therapy (Rituxan + cyclophosphamide, vincristine, and prednisone) to treat CLL and AIHA during my hemolytic crisis of October 2007. In the research of those frantic days, I ran across all the usual warnings about chemotherapy
side effects.

I also ran a
cross what, it turns out, are disagreements among top doctors about which drugs are more disagreeable.

Dr. Clive Zent, CLL autoimmune expert at the Mayo Clinic, told me:

"Vincristine has very
good activity against AIHA and ITP in many patients -- acts against macrophages causing RBC and platelet destruction -- and is thus a useful component of treatment. Vincristine also has activity against CLL. The drug has very little other toxicity and in particular minimal bone marrow toxicity. In contrast both cyclophosphamide and corticosteroids have a wide spectrum of serious toxicities. Obviously patients need to be monitored carefully for vincristine neurotoxicity and the drug stopped early if this occurs. In most cases full recovery is likely.”

Dr. Terry Hamblin, the well-known UK researcher and clinician, had another view of vincristine:

“ . . .
It also has the added side effect of peripheral neuropathy. Experience can be dangerous here, too. Perhaps I am unfairly prejudiced against the drug after seeing an old lady confined to a wheelchair for the rest of her life after just one dose.”

Well, me, I’m not an old lady right? As my grandma from the Old Country might have said, “You are young and strong like bull.” What could go wrong?

* * *

Vincristine received FDA approval in 1963 under the trade name Oncovin, which is
the “O” in R-CHOP, another chemo regimen that node-heavy CLL and lymphoma patients sometimes find themselves experiencing. The drug is a derivative of the Madagascar periwinkle, formerly known as “Vinca rosea,” and had been used as a folk remedy before its refinement for cancer purposes.

I have provided pict
ures of this very pretty plant and I can almost see the lemurs of Madagascar swinging about by their tails and chomping on the inviting foliage -- until peripheral neuropathy sets in and they all come crashing down from the branches with a thud.

My doctor, Dr. Belle, made a good call on the first day of R-CVP therapy back in October ‘07. Because my heart was under extra stress (my hemoglobin was down to 6.8), she ordered what she called a “baby dose” of vincristine. I would norma
lly have received 1.4/mg per meter squared -- around 3 mg given my body weight. Instead I was given 1.4 mg total.

That's all the vincristine I have ever had because it turned out that I am highly sensitive to it. Within days, peripheral
neuropathy (numbness of the fingers) set in, which lasted a couple of months. My vision became blurred, which at first I blamed on all the steroids I had been taking to control the AIHA. But this was a marked blurring, which set in over a few days, hung around for several weeks, and then resolved. Given these symptoms, Dr. Belle deleted vincristine from my other two rounds of treatment, with my blessing.

* * *

Months later, in the Spring of ‘08, I began to notice what I called a “creakiness” in my legs. If I sat for awhile, my thighs would tend to fall halfway asleep and I would be very stiff when getting up. I’d walk like an old man -- weakly, unsteadily -- for a minute or so until I got “warmed up.” Even
then, when my steps were more or less normal, I experienced a subtle achiness and discomfort that I had never noticed before.

I was also having trouble being limber: Let’s say you’re laying on your back with your left knee bent. You want to raise yo
ur right leg up in the air and cross it over the left, resting it against that bent knee. I was having a lot of trouble doing that sort of thing. I would need to be using my arm to pull my right leg up and over. My leg wasn't dead weight, exactly, but it didn't want to move on its own very easily.

Getting down on my knees to look for something on the floor became an almost superhuman challenge. That's because getting back up was nearly impossible, with most of the effort having to come from my arms, grabbing hold of armchairs and tables and such to give me enough leverage to stand.

At night, I would toss and turn in bed. My hips would ache, especially where the thigh muscles seemed to attach. This achiness would generally stay with me throughout the day to one degree or another. I spent a lot of time grumbling at the mattress, which is made of pure latex rubber and had never given me such trouble before.

My primary care physician had no idea what might be causing these symptoms, and Google searches only led me to a host of scary-sounding websites that discussed in detail everything that can and will go wrong with the hips.

I eventually laid it at the feet of the steroids I had been on -- loss of muscle mass does indeed accompany steroid use. The thing is, that mass comes back as you use the muscles again. And no matter what I did -- which included several sessions of physical therapy last summer -- I did not get better. Things just stayed the same.

Until a few weeks ago when, like a storm lifting, my hips and legs went back to the way they used to be -- suddenly and unexpectedly -- over the course of no more than two days.

Which is when the light bulb went off and I realized that I had been experiencing del
ayed symptoms from that baby dose of vincristine. That the Madagascar periwinkle might have been the source of my trouble had occurred to me before; but compared to the finger numbness and blurred vision, the onset of the creakiness was delayed enough, and the effects lasted so long, that it didn't fit the pattern of what I expected, especially since I'd had such a small dose. So I blamed the steroids.

If you look at the dose-limiting side effects chart of this PDF on vincristine, you’ll see that symptoms are defined as immediate (onset hours to days), early (days to w
eeks), delayed (weeks to months), and late (months to years). Peripheral neuropathy gets an “early,” but in my case the leg part of the problem was definitely “delayed.”

And for the record, let me quote:

Neurotoxicity involves peripheral, autonomic and central neuropathy. I
t is the primary and dose-limiting toxicity of vincristine. Most side effects are dose related and reversible, but neurotoxicity can persist for months after discontinuation of therapy in some patients, and in rare cases may be disabling.

Peripheral neuropathy is the most common type of neuropathy and deve
lops in almost all patients. Loss of deep tendon reflexes, peripheral paresthesias, pain and tingling can occur. If therapy is prolonged or high doses are administered, wrist and foot drop, ataxia, a slapping gait and difficulty in walking can occur.

I'll close with a cautionary note. Your mileage may vary, of course, but as it turned out my experience with the drug was a little closer to Dr. Hamblin’s than to Dr. Zent’s. Which goes to show you again that when it comes to chemotherapy (and CLL in general), we are all individuals. Statistics are general; results are personal.

The good news is that I am hypersensitive to vincristine, which presumably means it works effectively in my case. The bad news is that I am so sensitive to it that I can never use it again. At least my experience with it did not involve regular or large doses and massive system shock and permanent damage. So in a backhanded way, I guess I was lucky.

Interesting what sometimes passes for luck when it comes to cancer.