Two thumbs down on Rituxan + fresh frozen plasma

I came. I saw. I wasted my time.

That’s my verdict on Rituxan + fresh frozen plasma. Make that two thumbs down — mine and that of a patient who posted to the ACOR CLL List that his experience with it was “arduous and ineffective.” Better words to describe it I cannot find.

Our two anecdotal cases fly in the face of the results reported by Klepfish et al. in their paper Adding fresh frozen plasma to rituximab for the treatment of patients with refractory advanced CLL, about which I wrote here. The positive results reported on the five patients in the study might as well have come from an alternate universe as far as my experience goes.

R-FFP did nothing for my red counts or platelets. It was completely ineffective on even the smallest of lymph nodes. Indeed, once Rituxan was added it seemed to lead to a mild case of tumor flare, which eventually subsided with the nodes back at baseline. My lymphocyte count did drop, perhaps at a slightly faster clip than it did the last time I used single agent Rituxan. But the difference was not especially significant and, as my oncologist pointed out, the CLL cells could just as well have been seeking refuge back in the lymph nodes. As time has gone on, my disease has become more node-centric, to coin a phrase.

I underwent two rounds before we abandoned ship, pivoting to another treatment. I am now on monthly high-dose pulses of steroids accompanied by Rituxan, and we’ll probably add some cyclophosphamide. This is essentially a steroid-heavy version of the RCD protocol that got me through my hemolytic crisis in the fall of 2007 and gained me a pretty good remission for the following year.

It's also as close as I'm willing to get to R-CHOP, which is known for its effectiveness on bulky nodes. R-CHOP is probably as much fun as it sounds, and stands for Rituxan + cyclophosphamide; Hydroxydaunorubicin (aka adriamycin or doxorubicin); Oncovin (vincristine); and prednisone. I can't see doing vincristine again, and have no desire to subject my heart muscle to adriamycin (aka "the red death") if I can avoid it.

I'd rather go the FCR route than the HO route; perhaps, with final approval of Arzerra (HuMax-CD20) by the FDA expected soon, I'll be doing FCH when the time comes. In the meantime, steroids have a proven track record of reducing nodes. Eventually I’ll have another CT scan to see how we’re doing on the abdominal nodes, and we’ll consider following up with something more powerful to deepen and consolidate the remission. We might use Campath if we can get my abdominal node mass down to less than 5 cm. It’s a work in progress.

At least it’s working. The R-FFP involved a great deal of effort for no gain. The FFP was infused at the hospital, which was followed by a short trip to the oncologist’s office for the Rituxan. The hospital took forever to get the job done, forcing me to abandon plans to get two units of FFP and 375 mg/m2 of Rituxan in one day. In the first round there were delays because the hospital took three hours to type and match my blood. I did one unit that day, followed by half the Rituxan. The next day I did the second unit and finished the Rituxan. In the second round it took from 7 a.m. to 3 p.m. for the hospital to get two units in me (note the happy expression on my face in the photo above); by then it was too late to do the Rituxan, which was infused the following morning.

Marilyn and I learned a few things about FFP. One is that premeds generally are not given prior to its administration. Two is that a type and match is good for 21 days. Three is that you can add a second filter to the IV setup if you want to be as thorough as possible in catching any errant white blood cells. We insisted on the addition of a leukopoor filter (the circular jobby in the photo) so all the FFP was double-filtered. Four is that nobody seems to know how long the complement gained from the FFP lasts in your body -- could be hours, could be days. Marilyn spoke to the director of the blood bank and he said nobody knew, that no study had ever been done.

Hopefully these details will be of no use to you as you will sensibly avoid undergoing this protocol. I might add here that my CLL is not as advanced as those in the study, nor can it be called refractory. Although I have had a lot of Rituxan in my time (two of the patients in the study were refractory to the drug), I should have been a fairly easy patient, as it were. Of course, one thing we know in CLL is that some people respond better to a particular treatment than others, and this may just not have been my cup of tea, or bag of plasma.

One of the bags was especially murky and yellow, causing the nurse to comment that the donor must have had a fatty steak dinner before they gave plasma. Perhaps the donor should also have had some jalapenos, which might have given the protocol more kick.

Beyond living "la vida leuko"

The house is a mess. I don't have time for much of anything except what absolutely must be done, which explains why I'm not blogging a lot lately. Marilyn and I are living our lives inside a turbo-charged hamster wheel consisting of treatment for CLL; renovating the house and paying for renovation of the house so that we can sell it; and keeping our business ramped up to pay for as much of the above without going into even more enormous debt than we already find ourselves in (Thank you, Bernie Madoff! May you live to be a hundred -- in jail, of course).

It’s a three-ring circus with lots of elephants plotzing around. Sometimes the building shakes. And yet this morning, as I poured a cup of coffee into my Far Side mug in the beautiful new kitchen I won’t own much longer (we hope), I felt a sense of calm and optimism that I had almost forgotten had once been part of my life.

Call it a flashback to pre-CLL, when the mere weight of the world hung around my shoulders -- as opposed to the mere weight of the world plus the prospect of death and how to avoid the latter for as long as possible.

Here I stood in a half-done house, enjoying what for us Arizonans is a delicious morning of overcast, drizzly, and cool Memorial Day weekend weather. I could look through the mess around me and see that there was a future somewhere. A move sort of impending, an adventure even, a next step that despite being in large part about CLL is not all about CLL.

The CLL part, as I have alluded to in this blog many times, has much to do with the health insurance I have. Thank God I have it, but it’s Arizona-based only and it’s restrictive and won’t pay for a stem cell transplant when and if the time comes. So unless something miraculous finally happens in Washington requiring insurers to cover people with pre-existing conditions, I will have to follow the four winds to a place where there is a high-risk insurance pool that will take me. Let’s see what moves faster -- health care reform or the sale of this house. I am hoping for both by the end of the year.

The non-CLL part has something to do with getting one’s life back in order. A lot of things have been let slide around here since I was diagnosed in 2003. Plans and projects shelved, everything deferred to matters of disease and, gradually, economics. Spin it as much as I like, it’s basically been a depressing, unhappy time. After almost six years, I have decided that you can’t truly make a silk purse out of the CLL sow’s ear. Perhaps the mistake is in trying too hard.

Now things are changing. There are physical signs of it wherever I look. And maybe as time goes on I have developed less propensity to worry. Maybe I’m sick of living la vida leuko. Maybe standing in a new kitchen amid old debris symbolizes the ability to get things done, to get moving, to somehow take a powerful step beyond the inertia that followed the gut-punch of a cancer diagnosis.

Who knows, maybe I’m just responding to negative ions in the atmosphere. I’m not expecting the CLL road to get easier. I am just hoping that my ride along it -- Marilyn’s and mine -- might be somehow less bumpy, perhaps more focused on the scenery. It’s a beautiful world, really. Sedona is a beautiful place, but I have lived in beautiful places before.

Another one, I hope, awaits. Physical, metaphorical, lyrical. I’ll take what I can get.

Perhaps, I hope, I have taken a step and am just a little bit there already.

Might as well jump (?)

I don’t usually quote Van Halen songs in this blog. But then again I don’t usually run across a nurse who says deciding whether to have a stem cell transplant is like deciding whether to jump out of a burning building.

That’s what Theresa Brown, R.N., does today in a blog on The New York Times website. The title of her post is sobering: “When Cancer Treatment Might Kill You.” She tells the story of a young multiple myeloma patient who had an allogenic stem cell transplant and is now on a ventilator, having survived four surgeries in the last eight days following a bowel perforation. Doctors have removed his colon. This is all the result of Graft vs. Host Disease, aka GvHD.

What’s interesting here is the feeling that the nurses have about transplants: Mixed at best.

“It’s tough, and among ourselves there’s a strong feeling of “I would never get an allo,” because we know how bad it can be,” writes Brown.

Nonetheless, they don't think it's entirely hopeless.

“On my floor we have a book, an old-fashioned photo album filled with pictures of the transplant patients who are still alive. To many of the nurses on this floor, the specific details of these patients’ lives are irrelevant; all we care about is that they’re alive. They talk, eat, see their grandchildren, nurture their kids, love their spouses and enjoy their friends. They fill the place in the world that is uniquely theirs.

“For me, the book of transplant patients has a magical feeling. I sample its treasures by looking at a few photographs and then I put it away. I don’t need to read the whole book; just knowing it exists is enough. 'All these people survived,' I think. 'All these people are alive because of the work we do.' ”

I find that medical personnel speaking candidly can give you the best idea of what something is really like, or of what to avoid, what to do, what limits to accept, when to push harder. My oncologist, for example, absolutely recommends against staying in the hospital if it can possibly be avoided. The reason: too many germs. “If you have to go, bring your own pillow,” she told me once. “You don’t know what’s been living in the one they give you.”

Transfusion nurses have given me knowing looks indicating that I didn’t really need a transfusion. An ER doc, during the height of my October 2007 hemolytic crisis, told me that my instincts were right, that I was better off living with low hemoglobin until chemotherapy two days later than risking what I might pick up in a transfusion of non-irradiated blood. This went against the textbook, given that my hemoglobin was 6.6, but it was the voice of experience talking.

The point is, when medical people speak honestly, I listen. So I was quite interested in Brown’s conclusions about transplants.

“I compare his choice with deciding whether to jump from a burning building. Staying in the building means certain death. But if you jump, you might break both legs and take months to heal or sustain injuries serious enough that the complications eventually kill you. But you would be alive when you hit the ground. Maybe it will only buy you a few more rough years. But you might just walk away and live.

“When it comes down to cancer patients making the choice, a few decide to stay in the building. They opt for the quicker, surer death of cancer. Others, for different reasons, don’t have the option of a transplant. But even knowing the risks, I’m pretty sure I would make the leap, endure the free-fall, feel the impact, and hope to be one of the lucky ones who survives to walk back into the life that is waiting for me.”

That is, perhaps, the best metaphor I have run across when it comes to the transplant choice.

I know people who have jumped. Some survived and walked away, others managed with the equivalent of a broken leg. Some didn’t make it, or made it but faced difficult, often life-threatening challenges later on. Right now, one of them, a patient with aggressive CLL who sailed through transplant, is dealing with severe GvHD of the gut.

“This has easily been the hardest three weeks of our lives,” writes his wife. “Not knowing the plan or what was in store was and is so hard for us. . . . (He) isn't out of the woods yet by far.”

This patient was a textbook success until things started to go wrong. His case, not unlike the patient described in Brown's post, are potent reminders. They tell us, to take the metaphor in a slightly different direction, that we patients are playing with fire whenever we make a major decision, and especially when we decide to undergo transplant.

So, what will you do when the building starts to burn?

I will jump, but probably only when the flames get as close as I can stand them.

Rituxan + fresh frozen plasma

"Here I come to save the day!" -- Mighty Mouse

Modern-day alchemists have been trying to turn rituximab into Mighty Mouse for years now. The partially murine-derived monoclonal antibody, best known by its trade name Rituxan, can be used alone or in combination with chemotherapy to treat chronic lymphocytic leukemia. It doesn’t work too well as a single agent, but that hasn’t stopped some of us from using it that way because it is considerably less toxic than the alternatives.

When Rituxan attaches itself to B lymphocytes, including literally billions of CLL clones, it creates antibody-antigen complexes; it is the immune system’s response that determines to a great degree the effectiveness of the cell kill. That response involves activation of complement (more below) as well as the onslaught of our immunity army — macrophages, neutrophils, natural killer cells, and the like. Finding ways to boost the attack, through means that are also comparatively benign, has a been a focus of research.

At MD Anderson, they added Leukine to Rituxan in a study of elderly patients. Leukine is a Granulocyte-Macrophage Colony Stimulating Factor, which means it encourages the growth of granulocytes (neutrophils, eosinophils, and basophils) and monocytes, which mature into macrophages. This booster was somewhat effective, according to the researchers, and had the added benefit of upregulating CD20 expression. CD20 is what the Rituxan gloms onto on the surface of the B cells — the more CD20 you have, the better. (CLL cells don’t have that much CD20 when compared to those of, say, non-Hodgkins Lymphoma, on which single-agent Rituxan is much more effective and for which it was first approved by the FDA.)

Neupogen, which stimulates the growth of granulocytes but not macrophages, was advanced as a booster some time ago by CLL Topics. Despite a few mouse studies and the like, the idea never made it to clinical trial in humans, which means the evidence we have is anecdotal. I tried it in 2004 and 2005 and it didn’t do much for me, either in terms of lowering my lymphocyte count or, more importantly, reducing stubborn lymph nodes. It did allow me to experience the unusual sensation of rodents running around in my bones, which was actually the sensation of cells reproducing madly, not unlike that crazed Octomom we’ve been hearing about of late.

Similarly, I tried adding Beta-glucan to Rituxan in October 2006; there is an open clinical trial on this based on some evidence that it might encourage activation of the complement system. In my experience, this was, again, more theoretical than real.

The bottom line on all these boosters is that they are pretty mild, and therefore unlikely to do much for anyone except those who have mild CLL. Those like me, with progressing disease, need a little more mighty with our mouse.

+++

A promising area of booster research focuses on complement. Complement, a system of proteins circulating in blood plasma, forms our innate immunity. It is what gives some of us CLLers a fighting chance against infection long after our immunoglobulins have declined to frighteningly low levels.

Through a complex series of events, these proteins can be brought into action, focusing the body’s attack on the offending Rituxan-CLL complexes; macrophages play a close, interactive role with complement and even create some of the proteins found in complement. Derived from the Greek for “big eaters,” macrophages are powerful tools, capable of gobbling up huge numbers of CLL cells — or, if misdirected, as in autoimmune hemolytic anemia, red blood cells. (If there were a way to get macrophages to destroy CLL cells with the same efficiency that they go after red cells in AIHA, my CLL would be cured in a few weeks.)

It is this process — known as Complement Dependent Cellular Cytotoxicity — that accounts for much of the cell kill when Rituxan is used, so finding ways to tweak it has been a focus for researchers.

One thing they have found is that complement tends to be depleted rather quickly after Rituxan is infused. Typically, there is a cell-killing frenzy in the first 24-48 hours, which declines as time goes on. Successive Rituxan infusions are accompanied by less dramatic results as complement gets used up and has little chance to recover.

This has been my pattern. For example, when I was on Dr. John Byrd's thrice-weekly Rituxan regimen in October 2006, I reported the following in this blog:

The plan was to do Rituxan three days a week for two weeks, 375 mg/m2 each time. To this I added 2000 mg of Beta-glucan daily, the same product being used in a clinical trial of CLL patients at the University of Louisville, Kentucky. My CBC was done before each infusion, so I had the opportunity to see what was happening more frequently than in the past.

The treatment opened with a bang. My absolute lymphocyte count of 153,600 dropped to 48,200 within 48 hours. My chipmunky neck began to slim down. Another 48 hours put my count at 26,600. And that’s about where it stopped. By the middle of the second week I was reaching my Rituxan plateau, both in terms of nodes and counts. . . . My doctor suggested, and I concurred, that there was little point in doing the sixth infusion.

Aside from depletion, complement deficiencies have been identified in some CLL patients, especially those with more advanced disease. It is also thought that these deficiencies may be the cause of autoimmune problems.

+++

So what if we give the patient more, possibly healthier complement from an external source?

That leads us to the latest booster in the news, fresh frozen plasma (FFP), used in a small study of Stage 4 patients by doctors in Israel and Greece. The results were published last year under the title Adding fresh frozen plasma to rituximab for the treatment of patients with refractory advanced CLL. (The study appeared in QJM: An International Journal of Medicine, a peer-reviewed publication of the Oxford University Press.) The idea was to take FFP, filled with all those complement proteins, and give it to patients along with Rituxan.

Five patients with “severe, treatment-resistant CLL,” including three who had failed Rituxan, were given two units of FFP, followed by the standard dosage of 375mg/m2 of Rituxan. Treatment was repeated every one to two weeks for two to five cycles. The authors reported that “a rapid and dramatic clinical and laboratory response was achieved in all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph nodes and spleen and improvement of the anaemia and thrombocytopenia. This could be maintained over 8 months (median) with additional cycles if necessary. Treatment was well tolerated in all cases.”

The full paper provides some useful detail; I have a hard copy, purchased by my hem/onc, who finds the R-FFP idea intriguing.

All patients showed an improvement in hemoglobin and platelets. Rituxan usually improves these figures on its own, so it is hard to say how helpful the FFP was in this regard. But since we are dealing with a group of treatment-resistant salvage patients, my guess is that the progress is meaningful. Here are the before-and-after results for each patient: Hemoglobin — 9.0/11.1; 9.7/13.0; 6.4/11.0; 9.7/14.2; 10.2/14.7. Platelets — 40,000/92,000; 75,000/128,000; 13,000/58,000; 70,000/83,000; 117,000/140,000.

Of particular interest to bulky-disease-me are results on lymph nodes. Certain nodes were measured in each patient, with these before/after results: 7cm/2cm; 1.5 cm/normal; 6 cm/3 cm; 2 cm/normal; 2.5 cm/normal. Of course, CT scans would have provided a much more accurate measurement, especially since Rituxan — like most treatments — tends to be less effective on deep abdominal nodes, which cannot be palpated (measured by hand). While I would not expect R-FFP to perform miracles in node reduction, it does seem to be more effective than Rituxan alone.

The patients were followed for a median of eight months (range 4-24) and were described as having “durable” responses, “already well over a year in two of the patients.”

The authors discuss how FFP may work by correcting “qualitative and quantitative abnormalities of the complement system reported in patients with advanced disease. Even normal complement may be rapidly depleted as a consequence of RTX therapy. Thus, supplying complement and enhancing complement-dependent cell lysis by the FFP/RTX combination may be the crucial factor. However, this is not the only mechanism possible. FFP would have provided immunoglobulins which are frequently very low in most patients with CLL and could affect the kinetics of RTX metabolism. These postulates require further study.”

The authors understand that the results of their study need to be “confirmed in larger series of patients and in controlled settings.”

But they conclude, “Our initial observations in the treatment of five patients with advanced, treatment-resistant CLL suggest that the concurrent administration of plasma with RTX may afford a remarkable clinical response that can be maintained. The clinical and hematological improvement was observed within days and occurred even in three of the patients who had failed standard RTX treatment. The administration of plasma may have corrected complement abnormalities associated either with the CLL or with RTX action and appears to be safe. Further controlled studies are required, but even now, the possibility that RTX action may be enhanced by this simple, cost effective method should be noted.”

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Before we do our R-FFP happy dance, it is worth remembering that nothing we put in our bodies to treat cancer is risk-free. FFP has some potential side effects worth noting.

Since it is a blood product, FFP carries a small risk of viral transmission similar to that of red blood cell and platelet transfusions. While red blood cells are sometimes irradiated to kill viruses, this is not done to FFP. Donor-retested FFP is probably the safest form available; this involves holding the plasma in quarantine for a minimum of 112 days until the donor can be retested to check for viruses that may not have shown up during initial screening. This is a cumbersome process, which makes donor-retested FFP difficult to come by.

An easier “fix” is for FFP to be given through a filter that should catch any errant white blood cells that may be carrying an infection such as CMV. (The plasma is supposed to be free of white cells, but a few may sneak in.)

Upon infusion, allergic reactions occur in a small number of patients, usually consisting of urticaria (hives), a rash that can be mild to severe.

Antibodies in donor plasma can also wreak havoc. According to the UCSD Laboratory Services Guide, “Antibodies in the plasma may react with the recipient's red cells, causing a positive direct antiglobulin [Coombs] test.” In other words, it could open the door to AIHA. I should point out, though, that one patient in the Israeli study had AIHA, that his HGB rose from 9.7 to 14.2, and that he was described as “asymptomatic” after treatment.

Wikipedia reports that “the potential for alloimmunization is present, as demonstrated by the infrequent formation of Rh antibodies.”

One rare, unintended side effect is the possible development of Human Anti-Mouse Antibodies — in other words, the FFP might create an allergy to Rituxan! This can happen over time anyway, as this link explains, and it doesn't necessarily mean Rituxan can't be used again. Dr. Terry Hamblin once wrote, "HAMA responses can inactivate the effect of the rituximab, but not always. Sometimes giving more antibody overcomes the response."

Another problem, UCSD adds, is that “In rare instances, noncardiogenic pulmonary edema (transfusion-related acute lung injury) may develop due to antibodies in donor plasma that react with recipient leukocytes.”

I discussed some of these issues with my doctor, who noted that FFP is a commonly-used product that seldom results in a worst-case scenario. Two units, she added, is a relatively small amount. Patients need to be watched for blood clots, which can be warded off by taking enteric-coated aspirin. (Indeed, FFP has been given in cases of ITP since it helps with clotting.) Fluid retention is also a concern, and can be relieved by diuretics such as Lasix. Those issues, and possibly a mild rash, are more likely to present themselves than exotic antibody problems.

I am left to conclude that FFP is relatively low-risk as these things go, probably on the order of Rituxan itself. Rituxan, of course, is not benign for everyone; it can cause anaphalactic shock during infusion, and later on can cause severe skin problems, lead to viral reactivation, and so on. This doesn’t happen to most people, but it does happen. Similarly, FFP appears to be easily tolerated by most, and a real problem for a few.

+++

I am going to try it. I need to do something to keep my disease in check, and I have long been fascinated by the possibilities of this combination. I enter the protocol with my eyes wide open, knowing that it is experimental and that it may not work. If it were a run-of-the-mill Rituxan booster, I wouldn't even consider it; the potential of FFP to deliver a much more powerful punch has convinced me to go ahead.

My best-case scenario is a response similar to the patients in the study, especially in terms of lymph nodes. If the protocol can make a reasonable dent in my lymphadenopathy, it will have done so at minimal cost in comparison to the alternatives. Giving R-FFP a try is unlikely to burn any bridges, and I will know in fairly short order whether it works on me.

The most likely worst-case scenario is that FFP, like the other Rituxan boosters I have used, simply won’t do much. Outside the Israeli study, I know of one patient in the USA who tried R-FFP, every two weeks for three cycles. He reported to the ACOR CLL List that he found it “arduous and ineffective.”

In which case, should my results mirror his, it may well be time for me to go a more traditional route — perhaps high-dose steroids accompanied by Rituxan and Campath, or else Revlimid.

It is worth stepping back here for a little perspective as supplied by Dr. Hamblin. "Monoclonal antibodies," he once wrote, "are not the magic bullets that people hoped they would be." Cancer cells have defenses against attack, and the way Rituxan works is not completely understood, which is why so many booster ideas are better on paper than in real life. Perhaps there is no way to create a Mighty Mouse that is truly strong enough to save the day.

Nonetheless, FFP is the most promising idea to date. The theory behind it is sensible. The study results, limited though they may be, are encouraging. And you never know what your body might respond to. My doctor and I figure it is worth a shot. Based on my history, I expect to tolerate the protocol well. I have used Rituxan extensively, with no problems, and the one time I had a blood product (IVIg), it went smoothly.

A final note: All this Rituxan-boosterism may be rendered a moot point within the next year as HuMax-CD20 presumably gains approval from the FDA under the trade name Arzerra. HuMax, a fully humanized monoclonal — no mouse! — works much better with the complement system than Rituxan does. If I could wait for it, I would. But my CLL moves faster than the government.

The news hole

The "news hole" is a term from my newspaper days, meaning that gaping maw of blank space that has to be filled with stories for each edition. The news hole is like a black hole, except you have to fill it with something.

Living in an information society, we are constantly in need of, um, information. I remember when Marilyn and I walked into a Borders after our first book was published. There it was, Disco Nixon, taking up an entire table, gleaming under spotlights and screaming, “Here I am!” And after not too long it was gone from its prominent place, lost on a shelf on the second floor, just another of the 50,000 books published in 1995. Fifty thousand! Who has time to read 50?

In the world of 24-hour news, including TV and cable TV as well as website after website, there is also a news hole. Madoff victims are helping fill it (and hey, I’m glad to see Bernie was led off to jail today). I have had some interesting requests for interviews -- French television, a chain of German newspapers, Fox News, Inside Edition, and Geraldo, among others. I've been turning them down, though a free trip to France might have swayed me on the first one, but it was not in the offing. My stepmother Cynthia is so tired of media requests that she doesn’t even reply to them any more. CBS News, who cares? Katie who?

I don’t particularly enjoy seeing myself on television, unless there is a larger point to be gained from it, and that mostly doesn't seem to be the case. It’s interesting to be in this position, fielding these sort of calls and requests, getting a feel for what it’s like to be on the opposite end of the news hole. It involves a lot of inconvenience, with the added risk of being misquoted or portrayed inaccurately. The opportunities it creates are largely opportunities to be interviewed by more reporters.

But that’s not the big news around here. Marilyn and I are swamped with our home remodeling project, which is in one of the circles of Hell. While this will net us a nicer place to live, that’s not the purpose. We are preparing our home for sale. Bernie Madoff is making us free up our equity, such as it is. The contractor is here every day, creating noise and dust and requiring us to make a thousand decisions about everything, including the kitchen sink. So what’s more important to us than Geraldo is finding the right shower valve for the new tub in the master bath, running to Home Depot to pick up pavers for the downstairs patio, deciding whether the reverse osmosis faucet in the kitchen should be brushed nickel or brushed stainless steel.

Oh, yes. CLL is in there somewhere. I need to schedule a visit with my hem/onc in Scottsdale but that has to be coordinated with the arrival of our special-order shower pan for the hall bath, which we have to pick up down there next week sometime.

This house is our news hole. The remodel monster needs to be fed. And did I mention, speaking of feeding, that mice had chewed through the insulation and some of the wiring in our carport ceiling?

These are the issues I am living with front and center, surrounded by a jumble of boxes and furniture covered with dust, topped with that cherry known as sleep deprivation. Geraldo can wait.

A tip for fellow remodelers

If you want 10% off at Lowe's (and by extension Home Depot, since they accept competitors' coupons) get thee to a US Post Office and find a "moving kit." Inside there will be a Lowe's coupon for 10% off, good until June 30. (It's amusing to see that people are selling these on eBay, raiding post offices from coast to coast and making upwards of 20 bucks for lots of 10 coupons.)

Me and Madoff in the media

For those following my Bernie Madoff saga, here is a link to the piece that ran this morning on ABC's Good Morning America. You'll see me in the video report, as well as in a web story entitled "Madoff Scam Could Cost Cancer Patient His Life."

If you are visiting this blog for the first time and are interested in my original post on Madoff, which was read by a producer at ABC News and which led to all this attention, do take a look at Bernie Madoff Screws Leukemia Patient.

And if you're a CLL patient or caregiver, a special welcome. I hope my posts and the useful links on the right side of the page are helpful to you.

Besides the report on GMA, as they call it, here are some other links of interest: Madoff's World is an excellent article in Vanity Fair that quotes from my blog. ABC's World News Tonight ran a story on March 4 called Mrs. Madoff's Money, which included my 1991 video of Ruth Madoff's parents, Sol and Sarah Alpern, at our Catskills hotel, Sunny Oaks. Bloomberg.com interviewed me for this January report entitled Madoff’s Tactics Date to 1960s When Father-in-Law Was Recruiter.

All he needs is a red clown nose.

20/20 interview delayed

A few hours before tonight's 20/20 segment on Bernard Madoff was to air, I received a call from the producer and was told that my interview had been cut for time reasons, although they do plan to use it in a future broadcast. (Apparently there's a whole section they had to cut out, plus Diane Sawyer was given more time for an update on another story.) I'll hear more from the producer next week. So stay tuned -- I'll post an update here when I know with greater certainty when the interview might be aired.

As to the segment itself: It was predictably heavy on the sexy (as they say in the news biz) Palm Beach rich-who-got-burned angle and the celebrities-who-lost-a-lot (Zsa Zsa Gabor, Kevin Bacon) angle. And let's face it, Donald Trump is always going to get more air time than me.

My family's connection goes back to Madoff's early years and 20/20 didn't have time to get into how he got his start, how his father-in-law Sol Alpern (our hotel guest) got us involved in it, and so on. That really is another story for another time.

But part of that story is that many Madoff investors were not rich or famous. My father is a retired high school teacher, for example. My stepmom made money in the real estate boom in her neighborhood during the 1980s, buying and selling a couple of properties. Our family and the guests at the hotel who had Madoff accounts were, by and large, middle class to upper middle class people. Most people I know who lost money lost in the tens or hundreds of thousands, not in the millions. That element of the story deserves to be told, including, I hope, the way it impacts the life of your average chronic lymphocytic leukemia patient who doesn't have a Picasso to sell to make ends meet.

The report featured footage of Bernie sitting at his computer in his penthouse, presumably whiling away his hours of house arrest on the internet. One wonders if he is trying to scam those infamous Nigerian scammers.

I do appreciate the fact that 20/20 was willing to raise direct questions about who else might have been involved, who might have known that this was all a Ponzi scheme. Madoff's wife Ruth (my stepmom's classmate) and his sons and brother all received a mention. As someone who has been part of running a family business, it always made me feel more secure that Madoff had brought his family into the operation. But then again, come to think of it, people in the Mafia have families, too.

I'll be on ABC's 20/20 this Friday

I was interviewed this week by ABC News correspondent Brian Ross for a special two-part investigation into Bernie Madoff, the man behind the $50 billion Ponzi scheme. The first part will air this Friday on ABC's 20/20.

Readers of CLL Diary are already familiar with my family’s longstanding acquaintance with Madoff and his wife Ruth. A producer at 20/20 read my post Bernie Madoff screws leukemia patient and one thing led to another. The post goes rather heavily into the leukemia angle, and that is part of the interview as well. I discuss how my losses in Madoff and my family’s losses impact my health care, including a possible stem cell transplant. I also talk about the perspective that my CLL diagnosis has given me on life, which affects how I feel about the Madoff mess.

Part of my motivation for doing the interview was as a patient advocate -- to get CLL into the national media, however briefly or obliquely (and also to be living proof that you can be a younger person with the disease). If people find my blog through the story -- perhaps patients and caregivers who are not familiar with the online resources available -- then they will also find the useful links I have selected on the right side of the blog page.

The producers offered to fly me and Marilyn to New York City for the interview but it was on too short notice, so ABC sent a film crew here to Sedona. Besides me sitting in a chair talking to Ross via satellite, they also took some atmospheric shots -- me looking over old Madoff statements, me standing on my deck looking at the red rocks, and me walking across Highway 89A, which is the main four-lane road through town. It's a bit odd walking for the camera -- I was reminded of Monty Python's Ministry of Silly Walks as I tried to nonchalantly navigate my way down the street. I was also thinking about Miss America starting down the runway and tried not to walk like that.

I don’t know yet what will end up on the cutting room floor, or how the story will be handled -- I am a very minor part of the report, but perhaps a human face on the scandal. I do feel that the producers and Ross are dedicated to doing a proper, investigative job when it comes to digging into the Madoff affair, and that is long overdue.

Another transplant twist, in which I learn my chances of getting a good donor match

Many months after my visit to the NCI/NIH to discuss a stem cell transplant trial, I received a call from the clinical nurse in charge of finding donors for trial participants. In the 15 or so minutes we talked, Jennifer Wilder could not have been more helpful.

While I was rejected for the trial, one of the benefits of applying for it was that I was able to get a much better handle on my donor match situation. Before the trial, all I had to go on was a preliminary search of the National Marrow Donor Program (NMDP) database, which indicated there were 22 potential 6/6 matches at low resolution on the microscope.

That’s like looking through Mr. Magoo glasses and saying there are objects in the sky twinkling at night without knowing which are stars, which are planets, and which are airplanes passing by.

For their part, the NIH needed to do enough searching at high resolution to see what the prospect of a 10/10 matched unrelated donor would be, as that level of match is required for participation in the trial. It is also generally accepted as the desirable standard at all transplant centers. Their effort would have cost me thousands of dollars had I been paying for it out of pocket.

* * *

More on the results in a minute, but first a little background:

The bottom line when it comes to adult stem cell transplants is what sort of match you can get, and not all matches are created equal.

Sibling matches, for example, can mean less Graft vs. Host Disease (GVHD), which is what can happen when your new immune system comes into contact with your old one. But this also tends to mean less Graft vs. Leukemia effect (GVL), in which the new immune system takes on the CLL cells. Engraftment is harder since the CLL cells stick around, and relapse is more likely. Statistics show that if you are rolling the dice on a cure, your brother’s or sister’s stem cells are not the best way to go.

Matched unrelated donors are preferred -- those wonderful people who volunteer to help others in need. You’d think that out of some six billion people on earth there would be more than 10 million such donors, but those who need transplants are small in number and the need for donors does not get much publicity. (That prospective donors are often charged a small fee for testing does not help; one wonders what would happen if people were paid a small fee to agree to enlist, but that is another post for another day.)

A 10/10 match -- or better -- means the stage is set for a pretty good chance of engraftment and possibly cure. At the low end, Dr. Steven Pavletic of the NCI told me, an 8/8 match is acceptable. But it’s not desirable, and it’s something I would think twice about if it were all I could muster.

Then there’s the cord blood transplant, in which the rules change a bit: The level of match is not as important since the stem cells are pretty much unformed and adaptable to your system. Double cord blood transplants are a new thing, performed in adults at only a few centers. Dr. Paveltic described them as being riskier than unrelated, which indeed appears to be the consensus as of now.

A word is in order here about the mysteries of HLA -- Human Leukocyte Antigen -- typing, the complexities of which have caused smoke to come out of my ears as well as several other orifices on more than one occasion. For those of you who want to focus on the locus, the following are some links that provide further information, one from Wikipedia, one from CLL Topics and two from the NMDP, the first one for patients, the second one for professionals. (And aren’t we patients professional researchers at this point?)

* * *

Despite the statistics on CLL outcomes, the reflexive procedure at transplant centers seems to be to look for a sibling match first and then to look for an unrelated donor if that fails. I’ve got two brothers and a sister but each of them is a half-sibling. All are willing to donate their stem cells to my cause, none of which would be helpful. So thank you Rick, Dan, and Julie, but a sibling match is out.

Wilder told me that they found 15 6/6 unrelated matches at high resolution, looking at loci A, B, C, DRB1, DRB3, and DQB1. Two potential matches “would probably fall off for ethnic or other reasons," leaving me with a pool of 13.

(Ethnicity is important in all this, and I am a bit of an odd combination. My paternal grandparents were Russian Jews, who escaped the rule of Tsar Nicholas II and came to America shortly before the Russian Revolution. My mother was adopted, which I only learned following her death in 1977; after much searching, I narrowed her birthplace to the Irish immigrant community around Crown Point, New York. So I am something of an Irish Jew, evidently, which explains my demented sense of humor but which also puts me in a distinct ethnic minority.)

Of those 13 potential matches, they had additional data on four -- enough to get close to determining a 10/10 match. Of those, there is a 50% chance of one perfect match, Wilder said. The other three would be about a 10% chance of a 10/10 match. What lurks in the “mystery nine" would have to be determined through further testing.

Beyond this, there were 10 mismatched donors, probably only one of which might be as high as a 9/10 match.

Wilder said the odds of a successful transplant with a 9/10 match are “fairly decent.” The rule of thumb is that for every mismatch, successful outcomes drop by 9%.

A mismatch of one number at a locus is called an allele mismatch, she said, which is what I appear to have in three places when compared to the usual results for Caucasians. A mismatch of both numbers is called an antigen mismatch. Wilder said that an allele mismatch is not as bad as an antigen mismatch (fun reading here.)

“Do some mismatches matter more than others?” I asked.

The consensus is “yes,” Wilder said, but nobody agrees on what they are. For example, studies suggest that a mismatch at locus A-0205 is important but these studies are from Japan and could be important only within the confines of the Japanese ethnic group.

I have three “less common alleles,” she said, which means “a less common combination of numbers.” But she described my alleles as “nothing that’s all that rare.”

Obviously they’re rare enough to turn finding a 10/10 match into a bit of work.

One of my uncommon alleles is that A-0205. If you HLA-type 100 Caucasians, most will have 0201. Another uncommon allele that I have is at locus DRB1; I have 1305, and most would be 1302. Each of these counts as a mismatch. So a mismatch on the A-0205 alone means a 9/10 match, a mismatch on both the above means 8/10, etc. Transplanters do have an order of preference for where the mismatches are, but I didn’t get into the details.

Wilder said the bottom line for me is that with continued searching and typing of more donors, I would have a pretty good chance of finding a 10/10 match, with the prospect of a 9/10 in the background.

She searched databases worldwide. Wilder noted that people do join databases and a search in another year or two could “pop up some perfect matches.”

Which was polite of her to say, but my one perfect match, if there is one, could also get hit by a truck.

* * *

I have a case of CLL in which nothing is easy. I don’t have indolent disease. I don’t have horribly aggressive disease. I have progressing disease with fairly mild clinical symptoms, if you discount episodes of hemolysis due to AIHA, which isn't exactly easy to do. But my marrow is still pretty healthy, I don't have B symptoms such as fatigue and night sweats, and I am not prone to frequent or severe infections.

Alas, I have three out of four poor biological markers -- IgVH mutational status, ZAP-70 and FISH are all bad; CD38 remains good.

December's FISH test showed no new deletions beyond the 11q, and my 11q deletion appears to be stable when compared to results from 2007 -- the deletion shows up on just over half of cells tested. It also appears that I still have some ATM (programmed cell death) functionality. ATM is located on the long arm of chromosome 11, hence the tag of 11q. (It is not present on the short or “p” arm of the chromosome.) Monoallele deletion -- which is what I have -- means the relevant bit is broken off of the long arm of one of the set of two chromosomes #11. Biallele deletion means that both of the chromosomes 11 have lost the ATM gene. It stands to reason, and appears to be born out clinically, that the monoallele deletion is the half a loaf that is better than none; how long it will stay that day, given the vagaries of clonal evolution, is anyone's guess.

The downside of my 11q is that I also have extensive abdominal lymph nodes, as my CT scan of last month made clear. They're not impinging on anything important, but they have grown into a 13 cm by 15.5 cm mass, helping driving the disease, and a mass of that size is an indicator for treatment, according to the NCI guidelines.

I know where all this eventually leads -- transplant or die -- but it is not a pell mell rush, and so there is a little wiggle room along the way in terms of the what and when of treatment.

And what I learned from Wilder is that I’m not on Easy Street when it comes to finding a 10/10 donor, either. Still, she made it clear that there's a realistic chance. So let’s hope the one or maybe two or three people in the world’s donor databases who qualify enjoy quiet evenings at home with their air purifiers and heart-healthy diets.

Is this a slim reed on which to plan a long-term strategy?

The way I see it, the alternatives do not change because of the donor match situation. Basically, I can ride along doing chemo until nothing works on me anymore and I earn my scarlet “S” for “Salvage patient,” at which point I can make my peace with the world and go out gracefully.

Or I can go for a transplant at the best level of match I can get, even if it is not ideal: 9/10 perhaps, or cord blood, or maybe that 10/10 after all.

There is an anonymous quote I ran across that sums up my opinion: “There are always two choices. Two paths to take. One is easy. And its only reward is that it's easy.”

Dragging out the chemo is the “easy” choice here, but in a way it is also the hardest. It is a personal statement that “I accept that CLL will shorten my life, and that I will live three, five, maybe eight more years.”

Making the “hard” choice to go for transplant is saying, “I know there is a reasonable chance that I could be cured of CLL and I am willing to accept the risk of getting killed in the process, or living with inconvenience afterward, in order to have a longer life.”

In my humble opinion, and it is only that, so long as transplant is a viable alternative with a reasonable chance of success, the “easy way out” is akin to writing a suicide note.

* * *

But knowing that finding a perfect match will be a bit dicey does make me wonder about the advisability of jumping sooner rather than later. In making this decision, I am juggling a lot of balls in the air, or twirling a lot of plates on sticks, or tap dancing on the backs of several hungry alligators -- pick your metaphor.

As Dr. Pavletic told me, people don’t get healthier with age. I have no comorbidities (other cancers or diseases) that might reduce my chances of success. My heart and lung function are good. I am still chemosensitive, so my chances of getting a CR, or close, are decent, though hardly guaranteed. There will never be a better time than now, Pavletic said. As a reminder, he estimated that I have a 70% chance of a cure or long-term remission, perhaps a 15-20% chance of death, based on a 10/10 match. This tracks with everything I have heard for a patient in my situation.

Then again, despite my CLL and AIHA, I am enjoying pretty good quality of life. I’m 52. I can wait until I’m 55 or even a bit older before taking the leap. This guarantees me a few more years, time to enjoy life before risking that life. What I risk in waiting is the arrival of a comorbidity, watching the disease grow more stubborn and resistant to therapy, things that might ultimately reduce my chances of transplant success. What I gain in waiting is knowing that, barring a flying anvil with my name on it, I will probably be alive in three years. I am not risking a one in five chance of death.

This is a tough one. Push is starting to come to shove. Your thoughts are welcome.

Dopey, dopey, dopey

Reading CLL discussion groups, and reading between the lines in those discussion groups, I am very much aware that some people deal with the stress of leukemia by taking drugs. And by drugs I mean alcohol and prescription antidepressants as well as illegal substances such as marijuana.

What is causing me to write about this is the tempest-in-a-bong over Olympic champion Michael Phelps. The 23-year-old swimmer was photographed smoking pot; from the overreaction of some people, you’d think he had been caught strangling mermaids with one of those ribboned gold medals.

Well, give me, and Michael Phelps, a break.

Somehow the United States managed to come into existence and prosper for its first 150 years without any restrictions on what you could put into your body. Alcohol, pot, laudanum, opium, cocaine, magic mushrooms, you name it -- all were there and ready for the taking as this country built itself into something ever more prosperous and successful.

But American respect for individual liberty has always had a counterbalance: our Puritan heritage, which entered the 20th century in the form of the temperance movement that brought us the Prohibition of alcohol.

Big success that was, of course. Since then we’ve been on a bender Prohibiting just about everything else, and that hasn’t been working, either. Our last three presidents all used illegal drugs in their youth. Our drug laws are a joke, which is hardly funny because of the enormous waste of lives, money, and resources involved.

Within the past 15 years or so, medical marijuana has gained a foothold in some states. It’s obvious that anyone with a flimsy excuse -- I do believe painful bunions were once used -- can get a doctor to prescribe pot in California. At least when it comes to marijuana, the absurdity of Prohibition is starting to break down. Gone are the days, and they were real, when people were sentenced to years in jail for possessing a joint.

* * *

I’m not a druggy personality. I like the occasional glass of red wine, but I find that being fully awake and aware in the here and now is more trippy than living in a haze. I experimented with the usual stuff in high school and college, but it’s been 30 years since I’ve smoked pot.

The only drug that I ever truly liked was LSD, which I took a half-dozen times in college. Sometimes it was revelatory, sometimes merely enjoyable, sometimes a bit of both. I recall laying on my back in the organic garden at UC Santa Cruz, watching as passing clouds smiled at me. Another time I was listening to the music of Johann Sebastian Bach, which wove itself into something resembling a complex Persian carpet right before my eyes. Never once, despite hysterical media reports that indicated it might be a real danger, was I tempted to jump off a building to see if I could fly.

In life, the Darwin Awards apply, whether you’re on drugs or not. Some people can handle drugs and some can’t.

I think we’ve all seen what happens to friends and family when people can’t cope with them, or when they take undue risks to get high. A family that has always been quite close to ours lost its sensitive and talented middle child to some bad heroin one night in New York City; he was in his 30s. Another kid I knew and worked with many a summer led a life of drugs and dissolution, stealing from his own parents as an adult, until he managed to ruin his body to the point that it killed him.

And I know many more stories involving our legal drug. alcohol; I have seen it bring heartache and pain, emotional and physical, to people who could have and should have had happier and longer lives.

I also know people in their 70s who have smoked pot their entire lives and seem none the worse for wear. Just about everyone I was close to growing up has violated our Prohibition laws on multiple occasions and most of them are quite happy and successful today.

Which leads me back to my point: Our drug laws are dopey. They’re not respected and they don’t work.

People will do what people will do, whether they’re 23-year-old swimmers or 60-year-old cancer patients. Perhaps some day American society will be ready for an adult discussion of drugs -- why they should be legal (or at least managed more sensibly) and why you should make the choice to use them sparingly.

Until then, let’s drop the hypocrisy. Let’s zip the flimsy moral outrage. Drugs are everywhere. They always have been, they always will be, and in a free society Prohibition will always fail.