Dr. Rai's Christmas present

Sorry, it’s not a cure. But it is a short and interesting interview in today’s Oncology Times.

Dr. Kanti Rai, for those who don’t know, is one of the leading lights in CLL, father of the Rai staging system no less. In the interview he touches on some of the quandaries that doctors and patients face: How do you know when it is time to start treatment? What role do prognostic tests play and do they trump, or take a back seat to, clinical symptoms? What is the best treatment? How do you balance potential benefit against potential toxicity? What is the goal of therapy -- a MRD-negative remission or perhaps a lesser response as determined by traditional methods?

Here’s a line from the article that we can all relate to:

“During the past few years, the treatment options for CLL patients have become so numerous that both physicians and patients may be confused, Dr. Rai noted.”

If you want to get an expert’s feel for the lay of the land, as it were, this piece is worth your time. From what I have gleaned in my CLL travels, Dr. Rai offers some pretty sound advice.

You can download the PDF file here.

Now I have to get back to the eggnog.

Turkey season

If you ever see me and Marilyn on Dr. Phil, we will be discussing one thing: turkeys.

For Marilyn, the time beginning before Thanksgiving and running through Christmas is “turkey season.” This is when vast quantities of what Ben Franklin nominated to be our national bird show up in supermarkets. Whole turkeys are more difficult to find at other times of the year, especially at the cheap, promotional prices offered during the holidays.

Marilyn and I recently stood before a huge rectangular case of frozen turkeys, their rounded, white-plastic-covered carcasses gleaming under a bank of florescent lights.

“Where else can you get this much meat for 47 cents a pound!” Marilyn exclaimed, eyes aglow with that crazed look common to kamikaze pilots and Scientologists.

And so it begins.

There are people who are minimalists and there are people who embrace abundance. I am one of the former, Marilyn is one of the latter, and if there is any way in which our mutual compatibility has been tested over the years, it is this.

I am not exactly like the Buddhist monk who goes around with nothing more than the clothes on his back and a bowl for food. But left to my own devices I would live in a house where material objects are on the sparser side, where I would probably know everything I own and where it was.

But we do not live in that sort of house because, over time, life’s cornucopia has spilled forth upon us. Or, in the words of Marilyn’s sister, “You guys have a LOT of stuff.” Besides turkeys, Marilyn has some other -- ahem -- areas of interest. She has been known, for example, to appreciate the occasional objet d'art. And I am pleased to report that we have no shortage of towels. But her most passionate interest is books, a category that, like the universe, is ever expanding and has no end.

My only obsession is CDs, which I am forever pointing out take up almost no room around here. OK, that and stereo equipment. I have a component system in the living room, a bookshelf system in the kitchen, a portable stereo in the eBay room, a portable stereo in the library, and a component system in the bedroom, complete with two sets of speakers, which is connected to a large television. I argue that the latter is something of a home theater. Marilyn does not entirely believe me yet.

And we do have a couple areas of common interest: One is kitchen knives, gadgets, and pots and pans. Another is cats. There is a very thin line of sanity that we dare not cross when it comes to cat collecting. So, after our Pyewacket died in 2006, we decided to get just two, to keep each other company. But since cats are contraindicated in bone marrow transplant patients, and since I am headed that way in a few years, we are holding off and may volunteer to foster cats for the animal shelter instead. We need our fix.

But I digress. It is turkey season. Minimalist me would buy one turkey, enjoy it for the week it takes to eat it, and be done with it. Marilyn would buy enough turkeys so that we could build a small pyramid and worship Gobblor, the Lord of Poultry.

The real issue -- to me anyway -- is carrying capacity. We have one refrigerator/freezer. If we also had a chest freezer, I’d have no problem with indulging in turkeys. But we don’t. Space is limited. Turkeys are large. (Marilyn figures a 22-pound turkey has more meat than a 12-pound turkey and that once you’re prepping the bird, it’s not that much harder to prep a big one.)

We entered turkey season this year with one large turkey already in the freezer. It dates, I believe, from 2005. Then, not long ago, we won a turkey at the local natural foods store. Into the freezer it went. This required some rearranging and cramming.

“Don’t block the air vent in the back!” I blustered.

It is my argument that two turkeys in the freezer means that much less space for anything else. And given the rate at which we eat turkeys -- one a year, pretty much -- we are using precious room to store something that just doesn’t get et.

Now, in Marilyn’s mind’s eye we are always enjoying a delicious roast turkey. But she forgets that making said turkey is a long process. There is the four-day Defrosting, then T day itself: The Cleaning of the Innards, the Making of the Stuffing, the Cramming of the Stuffing, and the Emplacement of the Little Metal Spikes in the skin to hold the stuffing in the cavities. This is followed by the Enracking and the hours and hours of cooking.

Then there is the midway Turning -- keep it breast-side down the first half of cooking time and you get a turkey with juicy breast meat, but you need to turn it breast-side up to get a nicely browned breast. This means that halfway through yours truly must don the most heat-proof gloves available and lift said monster turkey, which is hot and has tiny, sharp metal things sticking out of it like a porcupine. The turkey must come off the rack without sticking to the rack or getting a leg caught in the rack, and then it must be turned over without dropping. This can be done but it is something that I look forward to like visiting the dentist.

Now, four days after this process, having finished yet another turkey dinner, and after a third glass of champagne, Marilyn has been known to say things like: “This was an easy meal seeing how much food we’ve gotten out of it.”

In an alcohol-induced glaze, I sometimes find myself agreeing. But why, then, do we not do it more often?

So, at last count we had two turkeys in the freezer. Rather than being satisfied, this only opened the door to Marilyn’s obsession. When she found out that our favorite grocery store had turkeys for 47 cents a pound, we had an argument. It was settled by a roll of the dice. She won, and so we found ourselves standing in front of the frozen case.

And we now have a third turkey -- weighing in at 22.74 pounds, the heavyweight champeen of the world! -- slowly defrosting in the refrigerator. Marilyn was tempted to get a fourth turkey but took pity on me.

My argument that there is no way two people can eat all the meat on a 22-pound turkey falls on deaf ears.

Did I mention that Marilyn doesn’t eat dark meat?

Calling Dr. Phil . . .


Marilyn and I and all our turkeys wish you a happy holiday season! See you in 2008.

I’m doing chemo now, Part 2; Choosing the right therapy for my AIHA and CLL

When last we left off in Part 1, it was a Thursday and I was meeting with my hem/onc, Dr. Belle, having ditched the clueless Dr. O’Leary. Hemolysis from my autoimmune hemolytic anemia had been going on for two weeks and huge doses of steroids were only marginally effective. I was feeling weak and anemic, but we had no idea until after my office visit, when blood labs were run at a nearby hospital, that my hemoglobin (HGB) had plummeted to 7.0. What we did know was that my condition demanded immediate attention, and that chemotherapy of some kind would commence the following Monday.

We discussed the options. As readers may recall, I had been undergoing treatment for AIHA since March and had relapsed twice, the most recent event occurring when Dr. O'Leary attempted to step down my steroid to 4 mg every other day. It was becoming clear that my relapses were severe and that I was a candidate for treating the underlying CLL, which is what is done when steroids -- and failing that, Rituxan -- cannot control or resolve the hemolysis, which is the destruction of red blood cells. Let the hemolysis continue unabated and the result is death.

“The general thought on AIHA,” Dr. Terry Hamblin has written, “is that it should be controlled by steroids alone, but if it is impossible to control when the steroids are tapered then the underlying CLL needs to be treated. . . . About 30-40% of AIHA is controlled by steroids alone and does not require any treatment for the CLL.”

Hemolysis in many AIHA patients is more gentle than it has been in me: In the two weeks prior to my arrival at Dr. Belle’s office, my HGB had fallen from 12.4 -- close to normal -- to 7.0, borderline transfusible. Indeed, it reached transfusion territory -- 6.7 -- on Saturday, two days after I met with Dr. Belle.

To FCR or not to FCR, that was the question

The first thought Dr. Belle and I had was to hit it hard, which meant FCR. Despite the risks involved that have been well-documented here and elsewhere, FCR remains pretty much the most thorough and effective treatment regimen available for CLL. Indeed, a CLL expert with whom I had consulted several days earlier had suggested cyclosporin to calm the hemolysis, followed by FCR. However, this suggestion was made before we knew that my HGB was falling so rapidly. And as Dr. Hamblin has pointed out on the ACOR CLL List, “I do recommend cyclosporin, though it takes about six weeks to work.”

That six weeks was the monkey wrench in the plan. I clearly would not last that long, having lost an average of four-tenths of a point of HGB every day for two weeks. Tranfusions would not be a useful bridge here as they are of only temporary use; a unit of blood gives you about a one-point rise in HGB, which in my case would be hemolyzed away in two to three days. I also did not want to extend the stress my heart was under for several more weeks; bottom-of-the-barrel hemoglobin puts you at increased risk for a heart attack.

So, what about jumping right to FCR without the cyclosporin?

Fludarabine (as well as its purine analogue cousins pentostatin and cladribine) is a well-known catalyst for AIHA.This is because, it is believed, the drug suppresses the activity of regulatory T cells, which normally keep killer T cells from running amok and thus contributing to the establishment of autoimmune disorders. There have been cases of rapid and even fatal hemolysis following treatment with single-agent fludarabine. This information, from the 2006 American Society of Hematology Education Book, should raise a big red flag (boldface mine):

“Because of the association of AIHA with chronic lymphocytic leukemia, many people with AIHA can be expected to have been treated with purine nucleoside analogues such as fludarabine . . . In 1995, Myint et al reported on 52 patients with AIHA treated with fludarabine, in whom severe AIHA occurred in 12 (23%) after a median of four courses. Nine of these 12 had no prior evidence of AIHA. Eight were retreated with fludarabine at a later time, and severe AIHA recurred in 6. The authors opined that a disturbance of immunoregulatory T cells was responsible for the problem, in that T-cell lymphopenia is a recognized effect of fludarabine. Weiss et al reviewed this subject, and reported on 24 patients with AIHA following fludarabine therapy for chronic lymphocytic leukemia. Most of the patients developed the AIHA after one to three courses of drug, and seven (29%) died of complications related to the AIHA. Of 8 patients rechallenged with fludarabine at a later time, 7 had recurrent AIHA, and 3 died.”

There you have it again folks, the stark truth: People die of AIHA.

So the question came up: Would it be safe to use fludarabine if it was being infused in the company of cyclophosphamide and Rituxan, both of which have the opposite effect from triggering hemolysis, and both of which are used to combat AIHA?

Well, lo and behold, MD Anderson recently published an abstract on the subject of combination therapy and AIHA, with the pertinent results as follows:

“Fludarabine has been associated with AIHA, whereas both rituximab and cyclophosphamide have been used to treat this condition. Combining these agents with fludarabine may reduce the likelihood of AIHA. We report on the incidence, outcome and pretreatment predictors of IA [immune anemias] in 300 patients treated with fludarabine, cyclophosphamide and rituximab (FCR). Nineteen patients (6.5%) developed IA on or after treatment with FCR. Most patients (82.4%) with AIHA had a negative direct antiglobulin test (DAT). Additional markers of haemolysis (indirect hyperbilirubinaemia, reticulocytosis, low haptoglobin and elevated lactate dehydrogenase levels) confirmed the presence of AIHA in these patients. . . . No haemolytic crisis was observed during FCR therapy in eight patients with AIHA prior to FCR. Thus, the incidence of IA among CLL patients treated with FCR was comparable with historical rates. . . . Pre-existing AIHA need not preclude front-line FCR therapy.”

Good to go, right? Well now, wait a minute. As I have said once or twice, the key in life -- or in battling CLL -- is not to know all the answers but rather to ask the right questions.

Is FCR safe in patients undergoing active, severe hemolysis?

That was the million-dollar question. Look carefully at the MDA abstract. It does not address that concern. It says patients developed AIHA after treatment, and that most of them were Coombs (aka DAT) negative. Eight patients who had experienced AIHA previous to FCR did not have a hemolytic crisis (and do note the use of the word “crisis” here.)

This is all well and good, but I did not fit the description of those patients. I was in the middle of a hemolytic crisis. I was Coombs positive and all those markers mentioned by MD Anderson -- bilirubin, reticulocyte count, haptoglobin, and LDH -- were severely out of whack. I would be going into FCR therapy with active, nasty, life-depleting AIHA and hemoglobin so low that there was little room for error. My life was on the line here and I was determined not to proceed unless I was convinced it was safe. Dr. Belle shared my concern.

Alas, there is precious little information on this subject available on the internet. I have run across anecdotal accounts of hemolyzing patients being treated with FCR and the like. But as my mother used to say, "If everyone else was jumping off a cliff, would you jump off, too?" I wanted information that was a little more solid, and, as anemic as I was, I set out to find it.

I had recently read with interest a paper by Drs. Clive Zent and Wei Ding of the Mayo Clinic in Rochester, MN. Called Diagnosis and Management of Autoimmune Complications of CLL/SLL, it lays out several of the treatment options for autoimmune disorders. This paragraph caught my eye: “Refractory AIHA can be difficult to manage, with no consistently effective treatment options. Splenectomy can decrease hemolysis but is less effective than in management of ITP. An alternative therapeutic approach is chemoimmunotherapy with regimens such as rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), which combine drugs with single-agent efficacy in the management of AIHA. Despite of lack of published trials, our experience suggests that this therapy is frequently effective.”

Dr. Zent is Mayo’s resident expert on such matters and he was kind enough to correspond with me when I asked for some further information. It should be emphasized here that I did not ask Dr. Zent for medical advice; I was asking him to further illuminate issues raised in his paper and elsewhere. That he did, and it is with his gracious permission that I post his answers here to share with the patient community (any boldface in his comments, or elsewhere, is mine).

“Use of purine analogues (fludarabine, pentostatin or 2CdA [cladribine]) as monotherapy in CLL after AIHA is not a good idea,” he told me.”Use of FCR or PCR is very controversial. Although these combinations have been used without precipitating AIHA in some patients, we have seen recurrence of AIHA and ITP. My preference is to avoid purine analogues whenever possible. Am also concerned about use of alemtuzumab [Campath] monotherapy although we have used alemtuzumab and rituximab with good results in a few patients. Problem at this time is lack of controlled trials of any of these combinations in patients with CLL and autoimmune complications.”

(So, in case you missed it, it is useful to point out that not everyone shares MD Anderson’s confidence that FCR can be administered to patients with a history of AIHA. A patient’s case history, clinical symptoms, and long-term treatment strategy no doubt play a big role in deciding whether FCR is advisable at some point.)

I asked Dr. Zent about R+CD, which is Rituxan, cyclophosphamide, and dexamethasone, a protocol used successfully by Kanti Rai et al to treat steroid-refractory AIHA. It is similar to R+CVP, except that it lacks vincristine. Had they tried R+CD at Mayo, I wondered, and did the vincristine really add that much to it?

“RCD and R-CVP are usually indicated for patients who need treatment for both CLL and their autoimmune complications, less often for "steroid resistant" AIHA in CLL,” he replied. “We have tried the RCD protocol and also use the R-CVP protocol without vincristine for some patients (very similar to RCD). Dexamethasone at 12 mg/dose is equivalent potency and toxicity to the prednisone (40 mg/m2) of the R-CVP protocol.

"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.”

(On the subject of vincristine, I followed up with this question: If a patient develops any symptoms of neurotoxicity -- no matter how mild -- is that an indication to stop treatment with the drug? Can the drug be safely used later if the the symptoms resolve, or is it best not to use it again, period?

“There are no data that I am aware of that answer this question," Dr. Zent replied. “My suggestion is that vincristine use can be continued if all neurological symptoms and signs resolve at the time of the next treatment, that the dose should be reduced if minimal symptoms persist and the the drug should be stopped if marked symptoms occur.”)

Finally, I asked this direct question: What do you generally recommend for patients with steroid-resistant AIHA who are actively hemolyzing? Would adding a purine analogue at that point, in the context of FCR or PCR, be acceptable or is it possible to make the hemolysis even worse by doing so?

His reply:

“Would depend on whether the CLL needs treatment on its own merits -- and that is a complex problem. If actively hemolyzing and CLL does not need treatment would consider adding rituximab to corticosteroids and then adding cyclosporin if that does not work. Acute hemolysis treatment options also include IVIG. If actively hemolyzing and needs treatment for CLL as well, would then consider R-CVP, alemtuzumab and rituximab, etc. Using a purine analogue would be very risky even in combination therapy."

"Very risky" was warning enough for me. That answer confirmed my suspicions and led to a new direction in thinking.

Settling on a better choice

So if FCR was out, what would be the next best thing? What would deliver the punch to get the job done without exposing me to risky purine analogues?

There were two candidate therapies: R+CD and R+CVP.

The Rai protocol and its results in a small group of patients is described in a 2002 paper and a follow-up 2006 abstract. All the patients had recovery of hemoglobin, with 50% achieving Coombs negativity. For those patients, the mean duration of response was 23 months, as opposed to 8.8 months for those who remained Coombs positive. “This finding that Coombs conversion portends a longer duration of response suggests treatment goals for AIHA should be a conversion to Coombs negative, and not stopped with recovery of HGB,” the authors wrote. It should be noted here that all the patients in this study were Rituxan-naive, which I am certainly not.

I asked Dr. Zent about the aim of treatment: Do you regard achievement of Coombs negativity as the end goal of treatment? If it is not achieved with one regimen, say R+CD or R+CVP, is it worth following up with another -- say Rituxan plus Campath -- in an attempt to achieve that goal?

“The clinical end point of treatment should be control of hemolysis. This is sometimes achievable with a shorter course of therapy and sometimes needs maintenance therapy (e.g. longer term prednisone). Conversion to a negative DAT (Coombs) test does correlate with a better response. However this is not always achievable and attempting to achieve this goal can cause considerable toxicity in some patients. You may recall that up to 30% of all CLL patients can have a positive DAT at some time during the course of their disease, and only a small fraction will have clinically relevant hemolysis.”

R+CVP is usually used to treat Non-Hodgkins Lymphoma and Follicular Lymphoma and is not a choice, under normal circumstances, for the treatment of CLL. (Indeed, an older study of advanced CLL patients compared chlorambucil + prednisone to CVP and found no advantage for CVP. The addition of Rituxan no doubt increases the effectiveness of both regimens, but there is a reason why R+CVP is not a frontline choice in CLL therapy and why its use is best restricted to unusual cases like mine.)

While not especially marrow toxic and well-tolerated by many patients, vincristine can cause potentially serious problems. These include peripheral neuropathy, central nervous system difficulties, and damage to the optic nerve. (Because of this, some doctors just don’t like it; Dr. Hamblin, in a comment on Part 1 of this post, wrote that he had seen “an old lady confined to a wheelchair for the rest of her life after just one dose.”) However, as Dr. Zent pointed out, vincristine has potent effects against the out-of-control macrophages that chew up precious red blood cells, as well as against the CLL. Clearly, as with any chemotherapy drug, there is an element of risk; the question is, under what circumstances might the rewards outweigh that risk?

Marilyn and I discussed all this, Dr. Belle and I touched base by phone and e-mail, and I also had a long talk with a learned friend. The upshot of all this was to recognize the following: Of the three components of the Rai protocol -- Rituxan, cyclophosphamide, and a steroid -- I had already used two. Rituxan, of which I have had bucketfuls since January 2004, does not work as well in me now as it did early on. While still somewhat effective, it could not be counted on to work as well as it did in those Rituxan-naive patients described in the study. Similarly, I was becoming steroid refractory. The only new element was the cyclophosphamide. Would it be enough, even in synergy with the other two drugs, to stop the hemolysis, help turn my red counts around, and maybe even get me to Coombs negativity?

The chances of success appeared greater by adding another agent, the vincristine. Two new drugs would probably lead to a deeper response than one. R+CVP was the strongest response that I could safely mount given the seriousness of my situation. The lack of a clinical trial was not a big stumbling block as I regard Mayo as one of the very best centers for treating CLL. Their leukemia team is filled with bright, reliable, and upstanding researchers and clinicians. If they feel comfortable recommending it in their article on autoimmune disorders, I feel comfortable trying it.

And so, the choice was made and I began treatment on Monday, October 22. How it has worked out thus far is described in the “How I’m Doing” section below.

One last note: I had long considered that my next step in treating CLL after single-agent Rituxan would be steroids in combination with Rituxan. On a pulsed, occasional basis steroids can help Rituxan by pushing CLL cells out of the marrow and nodes and into the bloodstream, where the monoclonal antibody can more easily get at them. Steroids by themselves can also help relieve painful, swollen nodes, at least temporarily. But, as I have learned this year, long-term, rather high doses of steroids of the sort used to treat my AIHA provide a limited CLL remission and are accompanied by potentially problematic side effects, osteoporosis and loss of muscle mass being the best known.

My next line of defense was to be the addition of an alkalyting agent, which means chlorambucil or cyclophosphamide. The former is not used to treat AIHA and indeed can trigger AIHA as often as fludarabine, though the episodes are not so severe. The latter is used to treat AIHA and can provide an immediate result. That made the choice easy. That Dr. John Byrd had also told me that cyclophosphamide is effective in 11q-deleted patients was a bonus that I hope will net me a decent remission when it comes to the CLL.

Some cautions and conclusions

I have gone into detail here because AIHA is tricky and because many patients and some doctors, such as my now-fired Dr. O’Leary, are at a loss as to what to do about it. The seriousness of the situation is often overlooked. As Dr. Hamblin said in his comments on Part 1 of my post:

“There is no doubt that AIHA is a serious problem in CLL, and if it does not respond to steroids and stay responding then the CLL must be treated. There are no clinical trials that tell us how it should be treated (it would be very difficult to organise one).

“I have personal experience of losing patients to AIHA, but not many doctors have. So you need a doctor who has enough experience to take it seriously. Recently, I have been giving medico legal opinions on young doctors who fail to recognise AIHA in CLL or fail to take it seriously enough.”

My purpose here is to get you, the patient, to take it seriously -- and by extension your doctor. I have provided Dr. Zent’s comments, as well as Dr. Hamblin’s, in the hope that they will help you finesse the issue as they helped me. AIHA is under-discussed on the internet; good information is hard to come by. I hope I have helped to close that gap a little.

And it is a serious matter. Even if I get to Coombs negativity, I cannot count on it lasting forever. Rai’s Coombs-negative patients stayed that way for a median of 23 months. AIHA is now front and center in decisions I make about treating my CLL. It only confirms in my mind the eventual need for a stem cell transplant and in the meantime it dictates the choices I make. FCR, for example, is something I can only risk when Coombs negative and when all other measures, such as haptoglobin, are in the healthy range. Campath by itself is contraindicated for AIHA, which is why experts such as Zent use it in combination with Rituxan. In fact, this warning now appears on the Campath box: “Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath.”

In my research I did find a couple of recent abstracts from overseas in which single-agent Campath has been used to treat AIHA; apparently you can play Russian Roulette and win, but it hardly seems worth the risk when adding Rituxan increases the safety margin significantly. (Or as a friend put it, "There are morons everywhere.")

What I found most interesting about these abstracts was the description of the patients, whose AIHA had gotten almost unfathomably bad. I provide this by way of a warning to, again, take AIHA seriously. Here is the start of an abstract from Sweden:

“Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy.We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy . . .”

Those people had been through it all and were being kept alive only by blood transfusions. Is that any way to live? Here is another abstract, this time from Hong Kong:

“A 58-year-old man with warm-antibody-mediated autoimmune hemolytic anemia (AIHA) refractory to prednisolone, azathioprine, splenectomy, rituximab and combination chemotherapy, and with unacceptably high transfusion requirement, was treated with alemtuzumab. . . .”

That man could be me if I am not careful, or he could be you.

I asked Dr. Zent the following: Does AIHA ever simply go away for good following treatment, or is a patient who has it once always at risk for relapse?

“The answer to this depends on whether the AIHA was provoked by therapy (e.g. fludarabine) or occurred spontaneously,” he wrote. “Most patients with spontaneous onset AIHA will tend to have a higher risk of relapse -- this is a relapsing condition and needs to be monitored indefinitely. I am sure that a few patients will have long lasting remissions off all treatment, but this will be a rare and retrospective finding.”

In other words, if you’ve come down with AIHA spontaneously -- and there really isn't much rhyme or reason as to who is likely to get it and who isn't -- it is likely to always be lurking in the background.

My final advice is this: If you have pernicious AIHA that gives rise to episodes of serious hemolysis, get yourself to a leading CLL center, such as Mayo, for an evaluation. In my case there wasn’t time and my health insurance doesn’t cover care outside of Arizona, which leads the nation in cacti and skin cancer but not CLL research and treatment. (Within the next year I am going to do something drastic about this.) Do not “hope for the best” and “assume it will all work out OK” because your local doctor says so. (Who knows what would have happened to me had I followed O’Leary’s suggestion that I fight severe hemolysis with just 8 mg of steroids, as described in Part 1.) Do not wait, like some patients I know, until you collapse in the shower or on the street or until your heart fails because it is working well past overtime in an oxygen-starved environment. AIHA can be managed effectively, but it is obvious to me that this is a medical niche, not a common skill, and that you need to find the right people to help.

HOW I’M DOING

So far I have had two cycles of treatment, three weeks apart. The protocol is 375 mg/m2 of Rituxan, followed by 750 mg/m2 of cyclophosphamide and 1.4 mg/m2 of vincristine. As I have also been on methylprednisolone for months, that serves as a substitute for the “P” in the protocol, which calls for 40 mg of prednsione on days 1-5. Since we cannot pulse my steroid, we have kept me on it daily and began to step down once it was clear the hemolysis had stopped. I began the first cycle at 72 mg daily, the second at 40 mg. (Mayo sometimes adds Rituxan on days 8 and 15; given my long history of Rituxan use, Dr. Belle saw little reason to overplay that weak hand.) For the third cycle, which starts this Monday, I will be on 20 mg of methylprednisolone.

The hemolysis came to a screeching halt after the first treatment. Bilirubin and LDH had been high and were normal as of my Nov. 9 blood work. As of Nov. 28, HGB had recovered to 11, hematocrit to 34, and total RBC to 3.09. I am still Coombs positive, though I will do another two cycles at least and can expect a greater likelihood of conversion to negativity as time goes on.

As for the CLL, many lymph nodes have simply disappeared; one node I used to monitor in my neck, which never got much below 3 cm no matter what I did, is now the size of a pea and barely palpable. I can still find some pelvic and abdominal nodes, however; these are reducing but are going to be the last to go, if they go, which I think is increasingly unlikely.

My platelets are at 212, about 50 points higher than they had been, on average, for the last couple of years. The absolute lymphocyte count is way down. It had been at 180,000 before treatment, thanks in large part to the steroids kicking the CLL out of the marrow and nodes and into the bloodstream. It’s now at 20,000 and I can probably expect it to normalize, which is what it did for almost everyone in Rai’s study. Overall, while I am secretly hoping for a CR –- what patient isn’t? -- given the state of the nodes, I will probably get a good PR instead.

There have been downsides. The biggie is that I am highly sensitive to vincristine. Dr. Belle administered only 1.4 mg total during the first infusion, playing it conservatively because of my low HGB and the stress my heart was under. Within two weeks I developed a toxicity that led us to suspend use of the drug.

What I have is the most common side effect, peripheral neuropathy, or numbness in the tips of my fingers. According to a physicians-only website that lists drug side effects, a print-out from which Dr. Belle gave me: “Peripheral neuropathy: Frequently the dose-limiting toxicity of vincristine. Most frequent in patients >40 years of age; occurs usually after an average of 3 weekly doses, but may occur after just one dose.” That’s me. I have a mild case, fortunately, and it should resolve eventually.

I also had, for about two weeks, some mildly blurred vision, which also results from the drug, and which resolved completely.

I wish I had tolerated the vincristine better, since it would do that much more to batter the CLL and send me to Coombs negativity. We may yet use it again in baby doses if the peripheral neuropathy resolves. In the meantime, I am now basically on the Rai protocol, hopefully having gotten some good benefit from the vincristine that first time around. You do what you have to do and hope it works; as I said in an earlier post, sometimes you have to fight fire with fire and either might burn you. I have no regrets and still look forward to normalizing my red counts, perhaps achieving Coombs negativity, and getting a hopefully lengthy break from the AIHA.

I have also been dealing with elevated glucose issues -- the steroids contribute to this, but so does the cyclophosphamide, a delayed side effect of which can be hyperglycemia. I am monitoring my glucose levels daily and have been on a rather Draconian almost-no-sugar, almost-no-carb diet to keep it under control. This, too, should resolve when treatment is completed. (Interestingly, consumption of alcohol keeps the liver from producing glucose, so drinking brut champagne every night with dinner guarantees me a normal result in the morning. What sacrifices we must make for our health!)

For a while we also worried about another side effect of the cyclophosphamide -- somewhat low serum sodium and serum chloride levels, which can lead to kidney problems. At first I was drinking Gatorade Rain to restore electrolyte balance, but it has a lot of sugar and this was discontinued in favor of Inland Sea Water, an electrolyte product Marilyn found that has a high concentration of salt and no glucose, and which resolved these issues in a matter of days.

So, in general, I am feeling much better and managing the side effects of treatment effectively. So far no nausea, which is common with cyclophosphamide, and no hair loss. I don’t have a lot to lose anyway, and I have been losing my hair since I was 13, so alopecia doesn’t freak me out as much as it could.

ABOUT THE ILLUSTRATIONS

The graphics accompanying this post are from a video game called Re-Mission, which is designed for children and teens coping with cancer. It’s a great idea, and a great way to visualize killing cancer cells, which has been shown to be an effective complement to treatment. I imagine adults can play it, too. You can learn all about it here.

Second blogiversary

My, how tempus fugits. Another year of blogging has now passed and CLL Diary enters Year Three.

I recently made a point of rereading everything I have written to date; the purpose was to keep the blog in good running condition -- to do things like fix broken links, and to add updates and afterwords where I thought appropriate if I have new information or further comments that might be of use.

But it also gave me a perspective on how my disease has changed and progressed, and how my reaction to it has also. I feel a bit older and wiser about chronic lymphocytic leukemia now than when I started, and I feel as if I am starting to hit my stride in terms of perspectives on treatments, balancing risks and rewards, and so on. (Of course, every time I think I have things sort of figured out, something comes along to humble me again; 'twas ever thus with CLL.)

I do this blog for two reasons. The selfish one is that it serves as a creative outlet; I have been a writer all my life and, as they say, "write what you know." The second reason is that I have a genuine desire to help other patients and their caregivers, and if any of my experiences and perspectives prove useful to you, then it is profoundly gratifying to me. Eventually, after my transplant and my cure -- I am an optimist by nature -- I could see working as a patient advocate if there is some way of making a living at it. So far CLL has been a vast sinkhole for time, energy, and money.

I will continue CLL Diary for the foreseeable future, even as I expect the next year to bring some big changes in my life. More on those as they unfold.

And I will continue to follow the credo that I started with: to be honest and true, to discuss my bad choices as well as my good, and to tell it as I see it. Only then does this blog have real value, and the exercise of writing it serves to keep me honest to myself as well as to you.

Late night thoughts on chemo and CLL

I am sleepless in Sedona, up in the middle of the night, thinking. It is the writer’s curse to be filled with ideas at inconvenient times.

I have written a lot about chemotherapy in this blog without actually having had any (Rituxan being immunotherapy, and a lot easier on the system). Now I am having it, and am coping with both the joy of success –- watching my red counts recover rapidly and the color, such as it was, return to my cheeks –- and some of the side effects: I am highly sensitive to vincristine as I have some numbness in my fingers after just one dose, and it was a half-dose. The cyclophosphamide is challenging me with hyperglycemia –- which, on top of the effects of the steroids, means I am on a Draconian no-glucose diet, at least temporarily.

But I don’t care. The big picture is that my back was to the wall and I did what I had to do and I am glad it is working. That big picture is the thing we CLL patients constantly try to grasp, yet there are so many mirages in CLL Bizarro World that we are often left clutching a fistful of illusions.

So I want to say some things about chemotherapy and also about CLL, provide some perspective I have been gaining.

The CLL lullaby

The first brain muddle we patients get into is that we all have the same disease. There was a time a couple of decades ago, when CLL was poorly understood, when that appeared even to the experts to be the case. And when it also appeared that survival and response to treatment had more to do with luck than anything else. Now, while luck plays a role in everything in life, we know today that CLL is not the same for all of us.

A reader of this blog wrote me and said, “I know someone who has had CLL for 30 years.” When I first was diagnosed I began trolling the internet for stories of people who had had CLL for a long time, concrete examples to hold on to, and I began to write them down in a page in a journal. And then as time went on, I came to know some of these people myself. More power to them. They are alive after all this time because they have very indolent CLL, possibly this asymptomatic lymphocytosis that Dr. Terry Hamblin writes about, possibly something a little worse than that but still so low-level as to be kept in check by their own immune systems or to respond to therapy for a long, long time. These are the people with IgVH mutated status who also have things like a deletion on one arm of the 13q gene, and who are CD38 and ZAP-70 negative –- Chaya Venkat’s Bucket A and A+. For the most part they do not have great secrets to tell us about how to overcome CLL. They are not geniuses; they are fortunate. They overcome CLL because for them it is a low-level, indolent disease -– the very picture of the “good cancer” –- and it is not really the same disease that the rest of us have.

This is why prognostic tests are important. They do not provide a complete picture, but they do give us the outlines. They do not always follow true to form –- you can have good markers and bad disease, and more rarely bad markers and not-so-bad-disease –- but they generally do. There are no doubt prognostic factors that have yet to be ironed out, discovered, entered into the CLL vernacular that will one day show us more. But today’s tests -– IgVH mutational status, FISH, CD38, ZAP-70 as done at a reliable research institution as opposed to a commercial lab –- will tell you a lot about your CLL.

Not getting them done is, to my mind, just plain stupid. When you’re first diagnosed and you’re feeling scared and vulnerable for a while, I can see holding off. But after you’ve gotten your CLL sea legs and realized that you’re not going to keel over tomorrow, it’s time to grow up and get real. Knowing your prognostic score, as it were, gives you more of a fighting chance when it comes to choosing the right risk-adapted therapy and in planning a long-term strategy.

That is, of course, if you acknowledge and act upon the results and don’t go putting your head in the sand when you hear them. But putting our heads in the sand is one thing we do because we are human, and also because we are encouraged to do it from the very beginning. We are told we have the “good cancer,” which leads to complacency. Even if we are not aware of it, it gives us subconscious permission to ignore CLL, to downgrade it, to pretend it won’t hurt us. (The fact that most of us also have a period of years before the disease begins to significantly impact our lives reinforces this misconception.) We are told “you will probably die with it, not because of it.” Well, that is true if you have an indolent form. Or if you are diagnosed at, say, 70, when your natural life span is starting to skate on statistically thinner ice anyway.

But that is not true for us younger people, and I know people diagnosed with this disease who are in their 20s. I know a young mother who is in hospice. I know that for those of us who are younger than 60, unless we are blessed with Bucket A CLL, most of us will die because of the disease and not with it, and we will die earlier than we would otherwise. Except for those who are saved by a transplant, which is the only cure we have for now. So therein lies hope, and it is where mine resides.

Transplants are tricky. They might cure you, they might kill you. Chaya has written with cautious optimism about them. Terry reminds us that life after a transplant can be hard to endure. Like so much having to do with CLL, the results are individual. Some people do well with minimal fuss, others struggle with nasty issues of graft versus host disease. My view is that the risk is better than the alternative.

Doctors

Which brings us back to chemo, sort of, except that I have another tangent first:

CLL is a confusing world in which patients still have trouble getting it into their heads that one size does not fit all, and that we do not all leave the starting gate at diagnosis in the same shape (and that clonal evolution can also change the order of things). Unfortunately, this thinking is reinforced by legions of local hem/oncs who have the same idea. CLLers form a small percentage of their practices and they deal with much more dramatic cancers, where life and death is indeed compressed into months or a few years. In that perspective, CLL is comparatively a good cancer. But as John Byrd has been heard to say, the only good cancer is the one you don’t have.

The bigger point here is that in my unscientific estimation from reading countless patient accounts, roughly half the hem/oncs out there are incompetent to treat CLL and its complications to an adequate standard. They are not up on the current thinking on prognostics, they are not up on the latest treatments, they don’t even know to put patients undergoing treatment on prophylactic meds, they’re fairly clueless about the laundry list of complications such as AIHA and ITP, they have no sense of the subtleties of when to end “watch and wait” and when to start treatment, they are so undereducated and inexperienced as to have little ability when it comes to the art of medicine as it relates to CLL. My history of having to fire doctors is not uncommon.

All this speaks to why you should see a CLL expert. I’ve seen a few. They may tell you different things about what to do if you need treatment, but there will be a sound reason behind each of their approaches. One must remember that even our expert doctors can only make the best possible guess as to what is right, and that the art of medicine does not guarantee a particular outcome. ("We like to pretend that medicine is an exact science, and that is hogwash,” Dr. Michael Keating told a friend of mine.) This is true of doctoring in general, and I would be remiss if I did not say that there are many good, dedicated local hem/oncs like my Dr. Belle that do all they can do to provide excellent care in our oft-befuddling landscape.

So, seeing an expert is essential. As is finding a local doctor who does their best to stay current on CLL and who is willing to work with you to understand it even better. The quality of your doctor(s) is a prognostic factor that influences your overall survival just like IgVH and the other medical tests.

Chemo

Now, back to chemo. Like many patients, I started out after diagnosis being afraid of the word. “Chemo” is a loaded term in our society. It’s what desperate, really sick people do. It means a bald head that makes you stand out in a crowd. It means being attached to bags of fluids in a room filled with people who are fighting for their lives. It means relatives who suddenly look scared, friends who whisper. It means chemicals with a laundry list of potential side effects getting into your body. It is all these monsters crawling out from under the psychic bed, shouting at you in the face: This is serious! You could die!

The subconscious idea that we CLLers have a “good,” indolent cancer predisposes us to not want to believe that such a serious thing as chemo is necessary or even right for us. After all, many CLLers do go on and on and on without it. But we are not all equal out of that starting gate, remember?

I have long had trepidations about the side effects of chemotherapy, not so much the annoying, mostly controllable stuff such as bald-headedness, peripheral neuropathy, and high glucose. More the uncontrollable risk of developing disease resistance to further therapy, a mucked up p53 pathway, an immune system so suppressed that Richter’s gets going, the big picture kind of stuff. This is why I have sided with the school of thought that believes in graduated treatment, soft-glove first. Arguments of merit can be made for the opposite view, the “nail it” approach. I do not fault those who go that way. I am happy when I hear a patient say, “I had FCR and my report now shows no detectable CLL anywhere in my body.”

I have also had trepidations because I have seen chemo be, for lack of a better term, abused. Abused by those local hem/oncs who really should not be treating CLLers, the kind who treat too soon and who treat with, say, single-agent fludarabine –- years after CLL experts agree that it is no longer the right approach.

I have expressed all these things in this blog, but I have not expressed enough of the following, so it stands here to be said:

Chemotherapy is an invaluable tool that should be used when it is needed. It should not be avoided at all possible cost. It should be used at the right time, which is tricky in CLL, and which is why you need to see a CLL expert and/or have a good local doctor who understands the current guidelines for treatment and who has some grasp of the art of medicine. And which is why you yourself should educate yourself as much as you can.

Timing is everything; my AIHA made the decision easy for me. I am glad the chemo was there to deal with the problem. When macrophages are eating your red cells with the ferocity usually found only at Nathan’s annual hot dog-eating contest, chemo starts looking mighty user-friendly.

When I had my first round of R+CVP a couple of weeks ago and the cyclophosphamide went in and the vincristine was injected, it was simple, it was painless, it all came in clear liquid just like the Rituxan, just like the saline. That is how it looked physically. What was being injected, psychically, was power, was purpose, was hope. Drugs ceased being a compendium of potential side effects –- the trees -– and started looking more like something that would prolong my existence –- the forest.

As Chaya points out always, there is no free lunch. Perhaps I have set in motion some things that I will not be happy about later. But in the risk-reward scale, there is no doubt in my mind that the rewards were worth the risks. Sometimes we must fight fire with fire and either may burn us.

Finding out when the rewards are worth the risk to you is one of the keys to success in battling CLL. Taking action in that window of time is the right thing to do. I once wrote about opportunity costs, a concept that I got from talking to Chaya and her husband PC, whose familiarity with so many patient case histories has given them a good perspective on the lay of the land.

Not taking action, refusing to believe things are as bad as they are, hanging on to some subconscious idea that CLL is still a “good,” indolent disease that Joe Blow has been living with for 30 years without chemo so why can’t I, that is foolishness. Lullaby and goodnight.

The best rule of thumb I can come up with is this: If you have aggressive disease, treat it aggressively. If you have progressing disease that is getting you into trouble, treat it as intelligently as you can, but treat it.

And do not go it alone. Go it with a good local doctor, go it by seeing an expert, go it by reading CLL Topics religiously, go it by reading Dr. Hamblin’s blog and keeping abreast of his answers on the ACOR CLL List, go it by hashing out ideas with other patients in places like CLL Forum.

Sometimes I think I have spent too much time online, reading all those things, connecting with patients, learning from experts. Then, this year, when push came to shove, I found that I knew some things that had a profound and important impact on the quality of my medical care and therefore on my life. So stay online and learn, humbled though you will always be by the vastness of what you still don’t know.

Patient, you must be ever vigilant. You will never know all the answers but you must learn to ask the right questions at the right time.

Knowledge is power, wisdom is the proper application of that power. That is what to strive for.

Now, I need to go back to sleep.

I’m doing chemo now, Part 1: How the need rather suddenly came upon me

I am now undergoing R+CVP therapy to treat both my AIHA and CLL. I’ll explain that therapy choice in another installment, but for now, first things first. This is the story of how things turned from good to bad almost overnight; about how patients should sometimes trust their instincts more than their doctors; and about how there are dedicated, caring doctors out there who can help at pivotal times.

I once had a gun put to my head during a robbery. The assailant didn’t shoot, or you wouldn’t be reading about my struggle with chronic lymphocytic leukemia. But he easily could have, and I would rather risk a gun to the head again than have to deal with autoimmune hemolytic anemia (AIHA), which is a byproduct of my CLL. That tells you how much I hate it, and here is why:

The morning of October 4 dawned like any other in central Arizona; bright, warm, endless blue sky, freeways filled with drivers gabbing on cell phones and oblivious to the speed limit. I was in Scottsdale to see Dr. O’Leary, whom I had been seeing since May, after my previous doctor, Dr. Belle, was dismissed from the very same practice due to some sort of rabid doctor-on-doctor office politics.

Dr. Belle had been promising all summer to go into practice again and I expected to return to her when she did. But as time dragged on, I had gotten used to O’Leary. With his thick glasses, checkered shirts, and dyed hair, he reminded me of my high school chemistry teacher: nerdy, a bit set in his ways but not dogmatic, working at the same place a long, long time. Seen it all, done it all, had developed a pleasant persona for dealing with patients. He was one of the original partners, in practice since the 1980s, now comfortably lumbering on until retirement. He had even been voted one of the top doctors in a Phoenix Magazine poll, which is where friends get friends to vote to give each other more business. As I learned from my one-time visit with Dr. Lord, and was to find out with O’Leary, any poll of top doctors is useless. Readers, do not be fooled! You are better off picking a name out of the phone book!

A little background

Dr. Belle had managed my AIHA after it was diagnosed in March, and O’Leary took over after she left. He was there for my relapse in July, and he was there but not there for my relapse in October, which is what this post is about.

Those with a taste for my full chronological history can read these posts. But here is the brief review: My March AIHA responded overnight to high-dose steroids, which is the standard first-line treatment. I was also receiving low-dose Rituxan, which went on for 12 weeks, well after the steroids were tapered off. As it turned out, the low-dose Rituxan acted as a substitute for the steroid, extending my AIHA remission. I got some IVIg at the end for good measure and was sent out into the world in June, red counts pretty much normalized but still Coombs positive. I relapsed three weeks later.

I suspected I was relapsing because I noticed on a Tuesday that my urine was starting to turn a darker color -- an orange-red, which is the byproduct of the dead husks if red blood cells being passed through the kidneys. By Friday I was in O’Leary’s office, a CBC confirmed my suspicions, and I was back on high-dose steroids. Again, they worked like a charm. Overnight my urine turned yellow. As I began to recover, O’Leary threw in four once-weekly doses of standard-strength Rituxan, which is a common procedure with AIHA. I was continued on the steroids and he began to taper them down. My red counts achieved a certain stability, though the hemoglobin (HGB) remained just shy of normal and I remained Coombs positive, though less so than at relapse.

The doctor’s plan

When the morning of October 4 came around, things were looking pretty good. In early September I had been stepped down from 8 mg of methylprednisolone daily to 4 mg. I was a bit nervous about this, going to the lowest dose, but my office visit CBC actually showed a very mild improvement in the reds, so my mind was put at ease somewhat.

Dr. O’Leary seemed pleased as well -- so much so that he felt it was time to step down even further, which came as a bit of a surprise to me. He wanted me to start taking my 4 mg pill every other day, as opposed to every day. “This will give your body a chance to recover, get used to not having the steroids,” he said.

“Do you think this is a bit too soon?,” I asked.

“Well, we have to do it sometime,” he said, “and you seem to be responding well.”

This sounded logical enough to me, though I had an intuitive feeling we were potentially starting to skate on some thin ice. But there was no harm, I figured, in following the doctor’s orders and giving it a try. We agreed to meet again in a month. Marilyn and I left his office, had lunch at a Vietnamese restaurant, and figured we’d get on with our lives as we had before.

Code orange

And so, that very day, I took no steroid. And lo, by the next day my urine was suspiciously orange. And I told myself: “No, this couldn’t be happening.” But over the weekend there was a definite urinary color trend. I knew I was hemolyzing again.

I called the doctor’s office on Monday the 8th and reported to the nurse: My urine is turning orange-red, which probably means I am hemolyzing because that is what this symptom has meant in the past. And can I have a CBC order faxed to my local lab so that we can just verify whether I am right or wrong?

“I’ll talk to the doctor,” she said. O’Leary, like others in his practice, is not big on giving out his e-mail address or cell phone number to patients. One must traverse a wall of tone-deaf and largely incompetent nurse meat to pose a question. (And, by the way, this is a long-established, well-known practice in a wealthy community, so they have had ample time and money to get organized.)

That afternoon the nurse called back: “The doctor does not think it is steroid-related. He suggests you have your primary care doctor do a urinalysis.”

I was a bit in shock. “And the CBC?” I asked.

No need, I was told.

When Marilyn came in to ask how the call went, I said, “I’ve been dissed.”

After my anger and disappointment had worn off a bit, I contacted the physician’s assistant at my primary care doctor’s office. Both the PA and the doc are good, solid professionals. The PA agreed to the urinalysis and also to a CBC at my request and faxed the order to the local lab.

I went in for the tests. As I expected, the urinalysis showed no infection. It did not, however, call for a count of red blood cells in the urine. I have since learned that there are urinalyses and then there are urinalyses.

But the most important thing was the CBC: It was showing a drop in the reds, not dramatic but enough to prove my point: Oct. 4 HGB was 12.4; by October 8 it was 11.9. Hematocrit went from 37.7 to 33.8. Overall red blood count dropped from 3.69 to 3.29. Yes, these results came from different labs, but the trend was unmistakable.

On Tuesday I called O’Leary’s nurse again. I told her the numbers, which I had gotten via telephone from the PA. I asked if I should up the steroid. She said she would talk to the doctor after she received a fax of the CBC.

“Can’t you just relay the numbers to him in the interim?” I asked.

Oh, you mean as in trusting that the patient has a brain larger than that of a banana slug and can actually write down numbers on a piece of paper with accuracy?

“No, he’ll want the full report.” And I had no doubt she was being honest, as O’Leary is nothing if not a little anal about having everything done in what he sees as the proper fashion.

And so this took time, the getting the one end to fax the other, the getting the fax to arrive, the wondering where the fax went and the refaxing, all of which went into Wednesday.

At which point I finally spoke to the nurse again: O’Leary will squeeze me in on Friday. Don’t change the steroid.

Well, I had already started to cheat, adding a little more methylprednisolone here and there on the “on” days. I wanted to slow any hemolysis. There was no point in letting it get further out of control.

Friday, bloodless Friday

Marilyn and I arrived late at O’Leary’s, having driven two hours from Sedona and being delayed further by a traffic accident on the main freeway into Phoenix, no doubt caused by someone going 85 miles an hour with one hand on the wheel while gabbing into their cell phone about Dancing with the Stars.

The CBC was a shocker: HGB down to 9.3, as bad as in my July relapse. Hematocrit 28.8. Overall RBC 2.68. The drop had accelerated sharply since Monday, despite my cheating on steroids. Anyone with that bigger-than-banana slug brain could see the steroids were failing me.

When I saw O’Leary I basically told him I told you so, as nicely as I could, given that I was still working with him. There is a certain inertia in working with a doctor, and until this past week he had seemed to be on top of things and at least acceptably attentive.

Could I forgive him, could I accept the role that human error plays, could I be comfortable knowing that his lapse in judgment might have been only that? I had already forgiven him for trying to step my steroids down, which had backfired. It was not an illogical step. What worried me was his failure to take me seriously during this past week.

I was prepared to see what he said, but I now had an ace in the hole: I just learned that Dr. Belle was finally back in practice.

Sadly, O’Leary appeared clueless. Months before I had given him the Mayo Clinic’s new paper by Drs. Clive Zent and Wei Ding discussing the treatment of autoimmune disorders in CLL. O’Leary had seemed impressed that I had managed to snag so recent a document off the internet (I told him about CLL Topics, which had alerted the patient community to it, and he promised to check Topics out one day, which he finally did, and reported back that he was “very impressed.”) We had even touched on some of the options mentioned in the paper in our conversations over the months, including Rituxan, cyclosporin, IVIg, and R+CVP, as well as other ideas like Kanti Rai’s R+CD and even FCR.

So at some point, when he was most lucid, O’Leary was aware of the options; but I think he was not used to seeing patients with AIHA as bad as mine, and was wedded to what had worked on the last patient, and maybe the one before that.

At any rate, O’Leary’s response to my CBC was astonishingly underwhelming.

“I don’t think I need to put you on the highest dose (72 mg) of steroids again,” he said. He wanted me to go back on just 8 mg daily. I was floored. Going back on high-dose steroids would be standard procedure as a stopgap, followed by something else ASAP.

And so, the visit began to take on the aura of the car wreck I had seen that morning. I was watching an accident happen. I did not trust him to address the immediate crisis or the long-term problem. This was the end of our relationship, and as he prattled on about something the plan became clear in the back of my mind: Get out of his office and take things into my own hands.

I got him to agree to double the 8 mg to 16 and got a prescription for a horse-choking supply of methylprednisolone. I put myself back on the 72 mg that had worked so well in the past, and I called Dr. Belle’s new office on Monday, scheduling an appointment for that Thursday. I expected that the high dose steroids would arrest the hemolysis, or at least slow it dramatically, and that Dr. Belle and I would figure out a more effective treatment for what clearly was and is a worse than average case of AIHA.

Saved by the Belle

I read an article recently on Time magazine’s website. It’s called Q: What Scares Doctors? A: Being the Patient. In one section, it discusses a study that shows that you are probably better off with a younger doctor, no more than ten years out of residency, than a doctor with more experience (my apologies here to the many older doctors who are indeed on the top of their game and whose expertise is invaluable to us all):

“But younger physicians may have other advantages – like a fresher sense of the latest standards of care. Many doctors have concluded that there is something of a sweet spot on the age-education-experience continuum. They seek out clinicians who are no more than 10 years out of residency, old enough to have some mileage, young enough to be up to speed. There is actually some hard data for this rule. A review published last year in the Annals of Internal Medicine examined the connection between a doctor's years in practice and the quality of care he or she provided. To the surprise of everyone – including the review's author, Harvard Medical School's Dr. Niteesh Choudhry – more than half the studies found decreasing performance with increasing years in practice for all outcomes assessed; only 4% found increasing performance with increasing age for some or all outcomes. One study found that for heart-attack patients, mortality increased 0.5% for every year the physician had been out of medical school.”

That quote could have been describing the difference between Deadwood O’Leary, as I have taken to calling him now, and Dr. Belle. Dr. Belle is young but a little bit seasoned. Besides having an excellent bedside manner, and especially an ability to treat patients honestly and directly as adults, she is interested in keeping up on the latest clinical trials and learning what she does not know. She seems excited about her work and gives her e-mail address and cell phone number to patients.

While starting out with no more knowledge of CLL and its complications that the average hem/onc, she has picked up some information through her experience with treating more than one patient. She knows I am pretty well informed about CLL and the choices I face, and we can have a free give-and-take conversation about it without any of the barriers that usually get in the way between doctor and patient. I should add here that, for all I know about CLL, I also know that my doctor has some experience and knowledge that I will never have. I cannot fix myself, nor would I want to try it alone. It is a partnership.

When we arrived at Dr. Belle’s new office on Thursday, it was a world apart from O’Leary’s. The colors were sunnier, the staff were universally pleasant, the vibe was “welcome,” not “sit there and wait for somebody to call you.”

When the doors to the back did open, we were happily surprised to see Dr. Belle’s nurse from the old practice, who left in solidarity when Dr. Belle was booted out. And then we saw Dr. Belle herself, who seemed much more at ease than she had been before. It was like a reunion of old friends, and then we got down to the business of my AIHA.

The practice being new, there was no machine on the premises to run a CBC; that would be done afterward, at a nearby hospital. In the meantime, Dr. Belle confirmed by physical exam that my liver was enlarged, the result of hemolysis, which could also be seen in the yellow cast of the whites of my eyes. I had no idea what my hemoglobin was at the moment but I knew I was feeling the effects of being anemic. While I had not thought the 72 mg would work a miracle as in the past, my urine had seemed more clear at times during the six days since I left O’Leary’s office. I figured my hemoglobin was perhaps stable, or had only dropped slightly since the 9.3 measurement at O’Leary’s.

We began to talk about treatment options; it was clear to both of us that steroids were failing me, that my AIHA was severe, and that we needed to treat the underlying CLL as well as the AIHA. Ideas were thrown out: use cyclosporin to stablize the situation and then follow with FCR, which had been recommended to me in correspondence by someone whose opinions I greatly respect. Consider R+CVP, which Mayo’s Zent wrote approvingly of. Consider Kanti Rai’s R+CD, which is essentially R+CVP without the V, or vincristine. In the end, we set an appointment for Monday for “chemo of an unknown kind.” We would each look into some of the questions about safety and efficacy that we had and would put our heads together over the weekend. Meanwhile, we’d see what the blood tests said.

A weekend of worse

Much to my surprise, and Marilyn’s -- and I want say here that we patients owe our caregivers the world, especially in such times -- my HGB that evening was down to 7.0. Hematocrit 20.4. RBC 1.67. The high-dose steroids had not been working nearly as well as I had hoped.

A hemoglobin of 7.0 is the line in the sand for transfusions for many doctors, including Dr. Belle. Below it, you get blood. At or above, you get left alone. We spoke to Dr. Belle by phone about the results. She offered the choice of doing chemo in the hospital immediately -- which would require an immediate choice of therapy -- but said she felt more comfortable doing it in the office on Monday. One reason is that stays in the hospital are to be avoided; the potential for a person who is already immune-compromised to pick up an infection is not to be discounted. We opted for Monday, and we agreed to do CBCs daily over the weekend to keep track of my hemoglobin.

Friday’s CBC from the lab here in Sedona showed a HGB of 7.8, which came as a pleasant surprise. I wondered if the steroids had finally begun to work their magic -- perhaps the 7.0 was my nadir and I was now starting to work my way back up.

Saturday’s CBC, at the lab in our regional hospital, disabused me of that notion: My HGB was 6.7.

I spoke to Dr. Belle by phone and she said she had suspected that the 7.8 had been an anomaly. She suggested I go on over to the ER, check in, and get two units of blood. Marilyn wheeled me there -- I was at the point of needing a wheelchair to navigate the long hospital corridors without getting unacceptably winded. I was given a fast pass to my own private room and an IV line was inserted into my left hand in preparation for the transfusion. In came the portable EKG machine -- result: normal. (This is important, as the heart is put under great stress trying to pump oxygen via a diminishing cadre of red blood cells.) In came the chest X-ray machine -- result: clear. And in came the doctor, who I’ll call Jim.

Jim is another one of those young doctors with enough experience to have navigated a pitfall or two, as well as the enthusiasm to care about each case. He looked me over, asked a number of questions -- Was I short of breath? Did I have blood in my stool? -- and concluded that I was asymptomatic, that my body had adjusted well to the gradual loss of red blood.

“If you were in an accident and had lost that amount of blood quickly, you’d be dead,” he said.

We talked a bit about my condition, including my expectation that in the longer term I would need a transplant to save me from CLL, and then I asked the million-dollar question: Is the blood irradiated?

Irradiated blood is recommended for immune-compromised patients. While it does not entirely reduce the danger of picking up a virus or something else that can put you in harm’s way, it is safer than plain old street blood. It would not be to my advantage to pick up CMV, let’s say, as I entered chemotherapy that was going to suppress my immune system even more than the steroids already had. Or to let slip into my bloodstream some other nasty that might rear its ugly head now or during a transplant.

The answer to my blood question was “no,” and Jim checked to see if it could be irradiated, and the answer was still “no”. Marilyn and I knew instantly that there would be no transfusion there that day. Meanwhile, a new blood test came back showing my HGB up a tenth, to 6.8.

Dr. Jim confided off the record that he didn’t think I really needed the transfusion given my asymptomatic nature and the dangers of picking up something in the blood -- or in the hospital -- that might cause me harm.

“Personally, I’d let it bleed down to about 4,” he said. This seemed a little low to me, but the message I was getting was this: In my practical experience you are doing OK, you can make it to Monday, better to play it safe by not taking on any additional risks. This dovetailed with our thinking. The nurse, who had overheard it all, also told us confidentially that we were making the right choice.

Jim spoke to Dr. Belle, who understood our concern. And so I was unhooked from the IV line and sent home, facing a $300 co-pay for an emergency room visit that wasn’t what I expected, but which was fruitful nonetheless.

I spoke to Dr. Belle. She said patients are routinely given chemo with HGB in the 6 range, so lack of a transfusion would not endanger the start of treatment.

It was Saturday at 4 p.m.. Treatment would start on Monday at 9 a.m. The only hitch: figuring out what it was to be.

In Part 2, I’ll explain why we chose R+CVP.

HOW I'M DOING - updated Nov. 5

For those interested in a health update, I have had one round of chemo and it appears to be doing the trick with minimal side effects. Today is Nov. 5 and the hemolysis has ended and the red counts are going in the right direction -- today's CBC shows hemoglobin is up to 10 two weeks after therapy, rising from 7.9 in the last five days alone. An added plus, of course, is that we are treating the CLL. My lymphocyte count has dropped from 180k to 50k and stubborn lymph nodes that were once 3 cm are now the size of peas. Next round of chemo is scheduled for Nov. 12.

And yes, UC Santa Cruz is my alma mater. This is where I learned to write down numbers on a piece of paper, which was quite a feat given the distraction caused by the redwoods (which is where all those yellow banana slugs can be found), the Pacific Ocean, and the other joys of college life, including meeting a certain Marilyn.