I’m doing chemo now, Part 3: The results

Well, the results are in from the R+CVP, which became R+CP after my fingers started to tingle and my vision started to blur . . .

The overriding goal of stopping the severe hemolysis, which in October had taken me on a trip that was a little too close to death’s door for comfort, was accomplished. As readers will recall, this hemolysis, or destruction of red blood cells, was caused by autoimmune hemolytic anemia, or AIHA. That condition is a result of my immune system having deteriorated into some kind of Keystone Cops routine thanks to all those CLL cells sending out silly messages.

My hemoglobin recovered from 6.7 to around 12, where it has stayed for the past six weeks. Hematocrit is in the mid-30s. Overall red blood count is in the 3.5 range. While none of these qualify as a return to normal, they do represent enough of a rebound that I feel pretty energetic. My body seems to have adapted to this “new normal” in my red counts, rendering me as active as I used to be, more or less. (It’s not like I ran marathons.) Now, if I were suddenly to find myself in the normal range, I’d probably feel that much more energy, but at this point it could be said that I don’t know what I’m missing. And given how bad things had gotten -- imagine being unable to bend over to put a dish in the dishwasher -- things are “normal” now by comparison.

The other pretty big success in the treatment was the reduction of lymph nodes. The swelling in my neck and under my arms is, quite simply, gone. My spleen is so petite that, if it were not for something of a pot belly and a little gender issue, I could compete in the Miss America contest. The only holdout nodes I detect are in the abdominal area, which are often the hardest to get rid of, especially in an 11q-deleted patient like me. However, even the mass of nodes on my left side (the “abominable lymph node”) is well reduced, not too noticeable, and no longer painful.

On the downside, two things didn’t work as well as I’d hoped:

One, the absolute lymphocyte count bottomed out in the low 20s, which means that I have a good number of CLL cells resistant to Rituxan and cyclophosphamide. (And god knows what else, but I’d prefer not to think about it.) Fortunately, the count has been stable for the past couple of months.

Two, I never converted to Coombs negativity, which was my not-so-secret desire in all this. Such a conversion would presage a longer remission from the AIHA. However, as Dr. Clive Zent of the Mayo Clinic pointed out to me, the goal of treatment is to control the hemolysis and not subject the patient to any more chemo toxicity than necessary. My hem/onc felt that after three cycles of R+C(V)P, we had accomplished that basic goal and were showing no signs of improving on things any further. I agreed, and that regimen will be held in reserve if I should begin another severe relapse.

It is living with that possibility that qualifies as the newest “new normal” that I have to adapt to. As Dr. Zent also pointed out, patients with AIHA seldom get rid of it. There is nothing I’d rather be rid of more, of course. Wrapping my head around the idea that it could return after such a “big” treatment is taking some doing. But experience teaches, and having a hem/onc who recognizes the severity of the problem also helps. So I am doubly vigilant, and that much more prepared, at any sign of trouble. (The monthly CBC has now become bi-weekly, for example.)

For now, I am continuing on steroids, currently at 12 mg of methylprednisolone daily, with the goal to go even lower. We will add in some periodic low-dose Rituxan, based on my experience with it last spring, in which it was able to control hemolysis when I was off the steroids. IVIg, another anti-hemolysis tool, will also be in the works as my Immunoglobulin G has now fallen below 300 for the first time. I am amazed that I have not come down with an infection, but perhaps I have more reserve immunity than the numbers would indicate. And we have been careful. Marilyn caught a bad cold and wore a surgical mask around the house while she had it, and she washed her hands constantly. Alas, no smooching, and I owe her a big one for taking such pains to keep me from getting sick. (Of course, we patients owe our caregivers not just a kiss but the world.)

As to the tingling fingers (peripheral neuropathy), they are slowly returning to normal. The blurred vision resolved after a few weeks. All this means I can use vincristine again in the future, albeit in very small doses. Had I been able to tolerate it better, it is possible I would have gotten a deeper and better remission, but those are the breaks in chemoland.

In the meantime, since I am in remission, I am trying to enjoy that aspect of it. The “new normal” has its rewards. This is a comparative “rest period” as opposed to the manic “what do we do/time to see another doctor/yes, I have good veins and you can use any one you want” period that accompanied my AIHA backslide in October.

Ultimately, though, my continuing AIHA saga, not to mention the rock-bottom immunoglobulins, illustrates that my immune system is pretty much shot. A stem cell transplant is becoming all the more necessary, and the time frame for it is no longer “some day” but more likely within the next two to three years. Investigating that course is now front and center in my ongoing CLL education.

As Roseanne Rosannadanna said, “It’s always something.”

The A-I-freaking-H-A

Not long ago, I was a reasonably content little watcher-and-waiter, using single-agent Rituxan to plug the holes in my CLL dike. Water still gathered around my ankles, but I muddled through the puddle with a quality of life that looked a lot like it did before CLL.

Now, after the arrival of autoimmune hemolytic anemia (AIHA), the unwelcome house guest that does not want to leave, I hear voices. Specifically, I hear the AIHA mimicking the imperious tones of King Louis XV of France. Louis, who toward the end of his reign sensed a collapse of the old order in the not-too-distant future, is reported to have said: “Apres moi, le deluge!”

AIHA is a sign of many things. It is a sign that chronic lymphocytic leukemia has gummed up my immune system enough to create a situation where my macrophages are attacking and destroying my red blood cells. It is a sign that my quality of life is diminishing because of my disease. It is a sign that my carefully nurtured avoidance of real chemotherapy is going to end sooner rather than later. And it is a sign that I had better have my long-term treatment strategy thought through and in place.

What is AIHA?

AIHA is a not-completely-understood fact of life for about 5% to 11% of CLLers, depending upon whose statistics you read. It can occur at any stage of the disease, though according to a recent Italian study it appears to be a bigger issue in the middle and later stages, in older patients, and in those who have had more therapy. It takes off when the immune system loses its ability to distinguish “self” from “non-self.” The end result is that the body creates antibodies to its own red blood cells and macrophages go on the attack, which leads to hemolysis -- literally the “breaking open” or destruction of red blood cells.

As Dr. Kanti Rai and his group at Long Island Jewish Medical Center put it in a 2002 study (bracketed comments mine):

“CLL is known to be associated with various autoimmune phenomena. AIHA is the commonest manifestation of such disorders in CLL. . . . The exact role of B lymphocytes in the pathogenesis of AIHA associated with CLL remains unclear. It has been suggested that complex interactions between the 'B' and the 'T' lymphocytes result in breakdown of self-tolerance, which eventually leads to the formation of antibodies against self-antigens such as erythrocytes [red blood cells] and platelets [which is the cause of that other joy of CLL, Immune Thrombocytopenia, or ITP].” The double whammy of having AIHA and ITP together is called Evans Syndrome.

AIHA can arise naturally but it can also be triggered by treatment with single-agent fludarabine or single-agent chlorambucil. When those drugs are used in combination with others, such as Rituxan and cyclophosphamide, the risk of triggering an attack is pretty much eliminated.

How do you know if you’ve got it?

A big problem patients face is doctors who mistake tanking red counts for marrow impaction when it is really an autoimmune problem. Drs. Wei Ding and Clive Zent of the Mayo Clinic go into this issue in a new article called Diagnosis and Management of Autoimmune Complications of CLL/SLL. This overview is worth reading and sharing with your doctor.

My own experience illustrates the need for patients to be on top of things. If I have learned one thing about CLL, it is to never, ever take what your doctor says for granted. Sometimes they are flat-out wrong.

Back in March, I noticed a suspicious drop in my hemoglobin (HGB) from one CBC to another -- it had been 13.0 on Feb. 28 and by Friday, March 9 was 10.8. (Hemoglobin is the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues to the lungs. The iron contained in hemoglobin is responsible for the red color of blood.)

When I mentioned this to my hem/onc, Dr. Belle, that Friday, she said it was probably just marrow impaction. This didn’t ring right to me, but it was at the end of our visit and she was already out the door. When I arrived back at her office the following Monday, absolutely convinced by symptoms (and research) over the weekend that I had AIHA, the head nurse looked at me like I was an idiot and repeated the same line. Only my insistence that I be tested for AIHA led to its diagnosis and treatment in a timely manner. Had I not made myself a pain in the ass, which is not easy to do when you are feeling anemic, I would have ended up in the emergency room requiring transfusions. On that Monday my HGB was 10.2. Two days later, when the diagnosis was confirmed and I began steroid and low-dose-Rituxan therapy, it was down to 8.9.

What made me suspect AIHA, besides the unusual drop in my hemoglobin, which had never been below normal, was three things: First, I woke up in the middle of the night to what only can be described as a marching in my ears. This was the sound of my heartbeat, working harder to provide oxygen to the blood. Second, I began to notice that my urine was turning an orange-red. This, it turns out, was due to red blood cells being destroyed and passed through the kidneys. Third, I began to have trouble doing things, such as walking up the stairs or squatting down to get carrots out of the vegetable crisper in the refrigerator, without becoming winded. This was subtle -- indeed, in retrospect I had been noticing small changes for a month or more -- but it definitely accelerated as the hemolysis increased.

My guess is that low-level hemolysis had been occurring since sometime in February, as even a HGB of 13, while at the bottom end of normal, is low for me. The hemolysis continued in early March and hit its stride over that weekend of March 10 and 11. By March 12, I was looking noticeably paler, which is no mean feat given my natural Pillsbury doughboy complexion.

Besides watching for symptoms, be aware of those blood tests. Monitor your total red blood count (RBC), your hemoglobin, and your hematocrit (HCT). The hematocrit is the proportion, by volume, of the blood that consists of red blood cells. When you get to what the infusion nurses call “10/30" -- HGB of 10, HCT of 30 -- you are in a potentially dangerous enough situation to require a transfusion.

Marrow impaction generally leads to a slow, tapered decline in RBC, HGB, and HCT. Anything suspiciously dramatic should raise an autoimmune red flag.

To diagnose AIHA, some of the more common tests done are haptoglobin level, reticulocyte count, and direct Coombs (aka DAT, or drect antiglobulin test). Coombs positivity means that antibodies are found on the surface of red blood cells. Haptoglobin is a protein that forms a complex with hemoglobin, and its decline is indicative of autoimmune anemia when associated with falling hemoglobin and increased reticulocyte count. Reticulocytes are baby red cells -- if the levels are high, this means the bone marrow is pumping them out to compensate for the destruction of red blood cells. If your marrow is impacted by CLL, you won’t be able to churn them out; if the count is higher than normal, your problem is likely to be autoimmune.

What to do about it?

Treatment can be geared to the AIHA specifically or to both the AIHA and the CLL. Again, like so much in CLL treatment decision-making, the question is of risks v. rewards. One can try to manage AIHA through a lighter touch, but this risks a sooner relapse.

Like CLL, AIHA is hard to get rid of completely. It can become a sleeping dragon, but the issue of relapse must be taken seriously, as I have learned the hard way.

The Mayo article points out that 65% of patients who respond to steroids, which are frontline management for AIHA, “will have evidence of recurrence of hemolysis as the prednisone dose is decreased and will require either maintenance corticosteroids or alternative therapy.”

Perhaps you don’t mind being on steroids for just about forever, but there are serious consequences to their long-term use, among these being a reduction or loss of vision. It also doesn’t make a lot of sense to take an immune-compromised patient, which you are just by having CLL, and put them on a long-term therapy that works by further immunosuppression. (Ding and Zent of Mayo point out that pneumonia is a risk here.) Like a big band aid, steroids only stop the macrophages from doing their job; steroids don’t get to the root of the problem. And what’s worse is that you can become refractory to steroids -- which means they won’t work on the AIHA anymore.

Ding and Zent (sounds like a discount warehouse store) point out that AIHA is not something that is likely to go away easily: “Autoimmune cytopenia can complicate all stages of CLL and can cause severe morbidity and mortality. Accurate and early diagnosis of the autoimmune cytopenia is important for optimal management. Therapy depends on the clinical severity of the cytopenia and CLL. Appropriate therapy can be highly effective but is rarely curative. All patients require careful long-term follow-up and early intervention for relapse.”

The message here is that AIHA takes your CLL to a whole ‘nother level. Especially for those with severe AIHA, like me, it may be worth pulling out some of those chemo guns that you’ve been saving.

Rituxan and steroids

Rituxan can be effective in treating AIHA and is often added to the steroids to create a combination frontline treatment. It can also be used by itself. After my CLL diagnosis in 2003, I tested Coombs positive but had no evidence of hemolysis, which is not uncommon. (According to Ding and Zent, “Autoantibodies specific for RBCs are detectable by the direct antiglobulin test in up to 20% of patients with advanced CLL but cause AIHA in only a minority of these patients.”) After a course of Rituxan for my CLL, I converted to Coombs negative. And then I went happily on my way, assuming that a nice byproduct of my continued Rituxan therapies would be that Coombs positivity, and therefore the possibility of AIHA, would be held at bay.

This may have worked for awhile, but it didn’t work forever, as I found out in March.

As readers of this blog know, in June I completed 12 weeks of low-dose Rituxan, which included nine days of methylprednisolone for the AIHA. It appeared to work, as the numbers show, even though I remained Coombs positive (more about those italics later):

On March 14, my RBC was 2.65, HGB 8.9, and HCT 26.9. On June 11, the RBC was 4.07, HGB 12.8, and HCT 38.5. And on June 19, I was treated by my health insurer to $18,000 worth of IVIG, which I figured would pretty much put the nail in the AIHA coffin. (IVIG, according to the Mayo authors, “can induce a rapid but usually short-duration response.”) It did clear up my sinus infection, thank you.

And the result of all that therapy was that I was pretty much hemolysis-free -- for another three weeks.

On Tuesday, July 10, I began to notice the tell-tale signs again. Darker urine was the first one, and then a little marching in the ears. I considered going to the ER but I had a longstanding appointment with my GP on Thursday, and one with my new hem/onc, Dr. O’Leary, on Friday. Blood work was taken Thursday and I began the steroids again pending the outcome; on Friday I learned that my RBC was 2.82, my HGB 9.4, and my HCT 27.7. The hemolysis had been worse than I expected.

As I write this I am on steroids again, 14 days worth of methylprednisolone at 72 mg/m2. The first week showed a marginal improvement in my situation, but Dr.O’Leary felt it was time to add some standard-dose Rituxan to the mix, so I am now scheduled for four weeks of that.

It is interesting to compare my first-week response from March, when I had steroids combined with low-dose Rituxan, and my first-week response in July, when I had steroids alone:

Methylprednisolone + low-dose Rituxan

. . March 14 . . March 21 . . Change (+)

RBC . . 2.65 . . 2.86 -- .21

HGB . . 8.9 . . 10.4 --- 1.5

HCT . . 26.9 . . 31.6 --- 4.7

Methylprednisolone alone

. . July 13 . . July 20 . . Change (+)

RBC . . 2.82 . . 2.91 -- .09

HGB . . 9.4 . . 9.8 --- .4

HCT . . 27.7 . . 30.6 -- 2.9

The Rituxan clearly boosted my response. How it works against AIHA is not exactly understood. Ding and Zent again: “Although rituximab is highly effective against the normal B cells responsible for synthesis of anti-RBC antibodies, this does not explain the rapid responses to therapy that have been observed.”

Dr. O’Leary is thinking, and he may be right, that four standard doses of the stuff will do more against the AIHA than all the low-dose -- which amounted to just two standard doses over 12 weeks -- did.

Avoiding yet another relapse, or biting the chemo bullet

And then what? So we get my HGB and HCT back to normal, or close. How do we prevent a relapse?

The key may be found in a recent abstract by Kanti Rai et al, following up on their earlier study (links to follow). What the researchers found was that patients who converted to Coombs negativity had a much longer remission on average (23 months) than those who did not convert (8.8 months).

“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.

So for me, as for many of you with AIHA, the big question is: Will the treatment I am doing lead to that conversion? Standard-dose Rituxan has done it for me in the past, but that was before I developed full-blown AIHA. Putting steroids together with standard-dose Rituxan seems like it is worth a try. If you can accomplish a task through less invasive means, do so. But given the seriousness of AIHA, by all means you have to accomplish the task.

If this treatment fails to give me that Coombs conversion, then it is time to consider what else can be done. And one good answer I have found is right in Kanti Rai’s study: Rituxan plus cyclophosphamide and dexamethasone.

Rai has used R+CD with success in steroid-refractory patients. The initial study showed that all eight patients treated achieved median hemoglobin of 14.2 for a median duration of 13 months. Later data with a larger patient sample, which included some with ITP by the way, indicated a mean duration of 22 months. (Many of these responders had already had fludarabine, it is interesting to note.)

An added plus for me is that cyclophosphamide is supposed to be especially helpful in 11q-deleted cases such as mine, according to Drs. John Byrd and Michael Keating. Besides controlling AIHA, the therapy might also help delay any incipient marrow inpaction, and it should provide excellent clearance of nodes. It is the direction I had been expecting to move toward anyway -- Rituxan plus an alkalyting agent -- and so it fits with my long-term plans.

And I am making those plans, which I will discuss in a future post. After Louis XV, the deluge indeed came and Louis XVI lost his head. I am hoping to keep mine.

Low- dose Rituxan – first round results

I have now completed my 12-week protocol of low-dose Rituxan, accompanied by methylprednisolone -- 72 mg a day over nine days. The purpose was to treat both my chronic lymphocytic leukemia and a nasty bout of autoimmune hemolytic anemia (AIHA) that reached its nadir on March 14.

The early returns are in, and the protocol did a pretty good job: It reduced my bulky lymph nodes by about 50% and lowered my absolute lymphocyte count (ALC) to within a few thousand points of normal. It did this while putting the kabosh (my medical term) on the anemia and restoring my red counts to at or near normal.

The jury is still out on how long these effects will last -- and that is a crucial question -- but so far, so good. Tomorrow I will finally be getting an infusion of IVIg, which should further help with the AIHA and which should also give me some much-needed immunity against infection, which was driving my white count up when treatment started March 12, and which also may have triggered the AIHA.

It is at this point that I should remind everyone that my results are what the researchers call anecdotal; that this was not a randomized, controlled study; and that your mileage may vary and probably will.

Background

The idea behind this protocol was inspired by the R + HDMP (Rituxan + high dose methylprednisolone) trials at UC San Diego. As readers know, I have used single-agent Rituxan several times over three years with diminishing results. So I looked into what could be done to boost my response without dipping my toes into traditional chemotherapy; as tempting as some of those chemo protocols are, the problem is that one can and will develop disease resistance to them. They cannot be reused indefinitely and they come with their own set of potentially dangerous toxicities. Ergo, it is best not to use them until you really, truly have to.

R + HDMP was one of the few ideas out there that did not involve either alkalyting agents (chlorambucil, cyclophosphamide) or purine anologues (fludarabine, pentostatin). UCSD has conducted two trials of R + HDMP in chemo-naive patients, one in 2004 and one just completed. I have corresponded with patients who have been in the trials and last year I made a trip to San Diego to see Dr. Januario Castro, one of the principal investigators in the trials.

Overall -- and this is my impression based on everything I have been able to learn -- it appears that participants are getting decent results, including normalized white counts, elimination of most or all lymph nodes, and dramatic reduction of CLL in the bone marrow. It also appears, from the perspective of time and distance, that these remissions are perhaps not as deep as those that can be obtained by such protocols as FR and FCR; rarely do they seem to be minimum residual disease negative, and patients are almost always offered Campath as a follow-up. Campath, a highly immunosuppressive monoclonal antibody, deepens and extends the remission.

When I saw Dr. Castro last May, he predicted I would get about 18 months out of R+HDMP. But there were certain factors that mitigated against my doing it. First, because I had had Rituxan in the past, I did not qualify for the trial at UCSD, nor would my insurance have covered regular treatment there; I believe the protocol is sufficiently tricky (read: potentially dangerous) that it should be done in a controlled setting where the doctors are experienced with it. Dr. Castro essentially agreed with me on that point and is not a fan of doing it off-study, aka “off-label.”

My then-new doctor, Dr. Belle, was also not interested in doing it off-label. She thought the amount of steroid used (1 gram/m2 of methylprednisolone x 3 cycles) was way over the top.

Indeed, I had to ask myself: Even if I could do R+HDMP in San Diego, would it be worth it for a relatively short 18-month remission? Would I want to follow up with Campath, which is an important drug – the only thing besides steroids that works on 17p-deleted CLL – that cannot be reused indefinitely?

In the end, all these factors conspired to cause me to abandon the thought of doing R+HDMP. So I began to think in the opposite way: could less be more, or could it at least be adequate? If I am probably not going to get a sterling, extremely durable CR regardless, what can I do to just control the CLL a little better?

Last year, around the time that I saw Dr. Castro, Dr. Ron Taylor of the University of Virginia was speaking at conferences about his studies of low-dose Rituxan in CLL. I went into this subject in some detail here.

If Rituxan has synergy with methylprednisolone, which it apparently does, based on both the San Diego studies and studies in the UK, then what can they do together at lower doses?

Dr. Belle was sympathetic to my quest to control CLL by low-toxicity means, and thus a little, informal protocol was born: LDR + LDMP (Low-dose Rituxan + low dose -- at least comparatively -- methylprednisolone).

I would be getting 20 mg/m2 of LDR three days a week for 12 weeks, and we would add the steroid in midway, after the blood counts had been reduced. This plan was turned on its head by the arrival of the AIHA, which coincided almost perfectly with the start of the LDR. As Dr. Belle said on March 14, while I sat in the infusion chair for my second dose of LDR, looking rather peaked with a hemoglobin of 8.9, “It looks like you have AIHA. How would you like to start the steroid early?”

And so we did. Starting March 14, and for nine days following, I took 72 mg of methylprednisolone each day (this being based on the standard amount of prednisone used to treat AIHA, recalculated to reflect my body mass and the differences in the pharmacokinetics of the steroids). After the ninth day, we stepped the steroid down over the following month.

My LDR + LDMP experience

The LDR, all 42 mg of it, was infused each time without premeds. Only once, when the bag was run through a bit too quickly, did I get an infusion reaction. Keep in mind that I am an experienced Rituxan user and that I know my limits, as it were. My advice to anyone using Rituxan for the first time, in whatever dose, is to make sure you are adequately premedicated with IV Benadryl, Tagamet, and a steroid such as Solu-Cortef -- all these things are designed to tamp down any infusion reaction before it begins. I did take allopurinol to guard against tumor lysis.

Some patients have had LDR at home via a self-administered subcutaneous shot. My insurance plan and the doctor’s office both had policies precluding this, which would have been convenient as we live two hours from the infusion center. This three-day-a-week schlep became so burdensome that we experimented, halfway through, with cutting back the infusions to two days a week (Monday and Friday). As it turned out, this made no difference in the rate at which the counts reduced, so we stuck with two days a week. Each infusion took about 20 minutes, and then we were off searching out yet another Vietnamese restaurant or buying unnecessarily large packages of things at Costco.

I took the methylprednisolone in 4mg tablets, meaning I was popping 18 of them a day at the height of it all. Overall, the steroid experience was a long, strange trip.

On the plus side, the steroid initially reduced my disease bulk by about 90%. I lost six pounds in the first two days, a lot of it probably lymph node and spleen weight. My neck was at its pre-CLL appearance within 72 hours.

But I continued losing weight; at first I thought it was muscle loss but the steroid appeared to be burning up fat cells instead. I lost 20 pounds over nine days and wrote here about my desperate efforts to eat enough to avoid losing too much weight (talk about living in a bizarro world . . .). As much as I hoped that I would be able to keep most of the weight off when I was done with the steroid, I hadn’t counted on the AIHA making aerobic exercise impossible. Not only did I not feel up to it much of the time, my heart was working overtime (I had less oxygen in my blood and it was under enough strain already. AIHA is not for the faint of heart, so to speak.) Gradually, then, I have regained just about all of the weight.

Steroids are also known for some other physical and psychological effects. My sleep was disturbed to some extent, and I found myself getting up earlier than usual and then having to take naps. Sometimes I had a little more energy than I should have had, but the AIHA tended to counter that. At certain times I had a sense of well-being that I am not generally used to; indeed, I found myself being a little more extroverted than normal. Sometimes, however, I would get worried, and I would obsess over a perceived problem or symptom. I wouldn’t call it paranoia, just a greater state of concern than usual.

One legitimate concern for me when it came to steroids was my history of squamous cell skin cancers. The immunosuppressive nature of steroids can lead to such cancers, as well as to infections running amok. Midway through the steroids I had my dermatologist gave me a complete exam, which I passed. As to infections, I was on several prophylactic meds to guard against them: Bactrim, acyclovir, diflucan, and later augmentin. Dr. Belle also ordered herpes, CMV and EBV titers to see if any of these posed a hidden danger. The last two were negative but the former was “high,” which led to the acyclovir: the last thing I needed in the midst of all this was to come down with shingles.

Steroids can cause a dramatic reduction of nodes in CLL, but the effects are rather transitory. I have been fortunate in that my nodes did not return completely within a month or two. Overall, I am guessing that they are at about 50% of what they were when I started. The painful pelvic nodes have quieted down considerably. My neck is still reasonably svelte. My disease bulk has probably been set back by about a year.

None of my previous Rituxan treatments were very effective on nodes 2.5 - 3 cm or larger. I tried adding Neupogen, EGCG, and Beta Glucan as boosters at various times but the steroid was the first thing that made a difference. I always intuitively felt that it would.

I do not know the extent to which the LDR may have prevented a complete return of the nodes once the steroid was tapered down. I did notice that, after an infusion, the nodes in my neck would recede a bit, feel a bit smaller. But this effect was transient and after a couple of days they would return to their baseline. Now that I am done with the LDR, it will be interesting (in a watching-a-traffic-accident kind of way) to see how fast they grow.

One of the mysteries in my results has to do with the reduction of the ALC. When I started on March 12, it was 162k and rapidly rising, probably due to an infection that may also have triggered the AIHA. After the steroids pushed things out of the nodes and marrow, the count went to a high of 361k on March 20. Then it dropped to 263k on March 26 and 92k on April 2.

Why such a dramatic drop? The LDR could not have been responsible for the entire reduction, especially as I wasn’t even using it one of those weeks (long story, another post). The steroid would not have been responsible for that much of the cell kill. My theory is that the antibiotics and antiviral drugs I was on finally put an end to that infection I mentioned, and that the CLL therefore naturally ramped down. It is also entirely possible that some of the CLL could have sneaked back into the spleen, liver and less noticeable nodes as the steroid was stepped down during that time.

I do know that once my counts were below 100k, the LDR reduced them, consistently, by 10-15k per week until a plateau was reached. The only bump upward came when, after I was off the prophylactic Bactrim, it appeared I had caught a new bug, or the old one had returned (monocytes and granulocytes also increased). I began the augmentin then and the counts resumed their downward course. They hit 8.6 on May 21 and then began to dither around, rising a bit, then falling again to a low of 7.3 on June 5. On June 11 they were at 8.4 and they were at 12.1 by June 15. Essentially, then, I hit my plateau about eight or nine weeks in. A whole 12 weeks of LDR is probably not necessary in my case.

That bottom number, 7.3, was lower than the low reached during my previous Rituxan therapy, last October, when the ALC dropped to 22.6. I was then using Dr. John Byrd’s thrice-a-week protocol of standard-dose Rituxan.

By comparison, here are my other lowest ALCs following Rituxan therapy, dating back to January 2004: First treatment 2.3, second 4.9, third 5.1. Considering how much Rituxan I’ve had since I started – almost 20,000 mg total – I think the 7.3 is a pretty good result. Keep in mind that it was reached by using the amount of Rituxan that would normally be given in less than two standard doses.

Worth a mention here is the effect that all this had on my platelets. They were at 197 when treatment began on March 12. They reached a high of 325 on March 19, likely because the steroids had emptied out the spleen. There was a slow decline to 151 on May 11. Then they dropped like a rock to below normal (baseline of 130) for the first time ever -- to 99 on May 18 and then to 85 on May 21. Dr. Lord made the assumption that I had developed ITP and now had Evans Syndrome, which is the double booby prize of having both AIHA and ITP. But it turns out he was wrong. The platelets began to climb back into the normal range, and were 135 by June 15. An anti-platelet antibody test turned out negative.

So, what knocked the platelets down? Going on nothing other than a hunch, I suspect the Rituxan. Last October, when I did standard-dose Rituxan three days a week, my platelets took a big hit during the first 48 hours, then they slowly recovered. I am guessing that some tipping point in their relation to Rituxan was reached this time.

It should also be noted that my immunoglobulins declined during the treatment, my IGG dropping from 746 on March 20 to 382 on June 15. It is suspected that Rituxan can erode IGG, but none of my previous Rituxans appeared to cause a decline, even though a lot more of the antibody was in my system then. Was it the Rituxan? Was it fate? What I do know is that at the higher number my IGG was pretty much ineffective at keeping away infections, so IVIg was in the cards for me regardless.

Last but by no means least, there’s the AIHA. (I say “by no means least” because once you’ve had it, you never want to have it again.) The rather dramatic hemolysis stopped immediately after I started taking the steroid. But I have been surprised at how long it has taken for my red counts to return to a semblance of normalcy. Apparently this is not uncommon and I am rather lucky: there are people who are on steroids for months and months to get a handle on AIHA. (Given my weight loss problem, I am not sure how I could have managed that.) Here are my red counts at their worst,
on March 14: RBC 2.65, HGB 8.9, HCT 26.9.
On June 11, RBC was 4.07, HGB 12.8, HCT 38.5
(Normal: RBC 4.7 - 6.10; HGB 13.0 - 17.0; HCT 36.0 - 52.0)

The bigger picture

In a discussion of AIHA on the ACOR list, Dr. Terry Hamblin once wrote, “Some cases of CLL present with AIHA, and indeed once the AIHA has been treated with steroids, the CLL is barely detectable.”

Given my bulky disease, it would have been too much for me to hope that the CLL would resolve along with the AIHA. But in some patients, those with fewer nodes and more indolent CLL, LDR+LDMP may enhance the chance of just such a remission.

Chlorambucil (CB) plus prednisone was once a fairly standard treatment for CLL. CB killed the CLL while the steroid reduced the nodes. Studies showed no improved survival by adding the prednisone, but it did help relieve discomfort.

Nowadays, with Rituxan available, some of that same cell kill can be accomplished without adding an alkylating agent. The methylprednisolone, which has established cell kill properties at higher doses, may retain some of them at lower ones, though this is not definitely established by any means, and it may also still exhibit some synergy with Rituxan.

In some patients, this combination may provide CLL control at minimal cost in terms of toxicity (while having the added bonus of combatting AIHA, which is a property of Rituxan as well as the steroid). Besides reducing nodes, it also clears out the marrow better than Rituxan alone.

Ideally, such a soft-glove approach should have been administered to me a year or two ago when my lymphadenopathy was less extensive. I did in fact suggest to my second hem/onc, Dr. Chopin, that prednisone be added to my standard-dose Rituxan in October 2005. She refused to do it, saying simply, “It’s not done.”

Well, folks, there’s a first time for everything. As far as I’m concerned, low-dose Rituxan is a no-brainer for most patients using the drug as a single agent. (I say this not only based upon my personal experience, but also upon Ron Taylor’s pilot studies and anecdotal reports from other patients.) Adding pulsed doses of methylprednisone that are consonant with the steroid dosages normally used in CLL is also logical.

Now, in my case, it remains to be seen how well this will ultimately work. Dr. Belle and I realized that the first 12 weeks would be just the beginning. On the very day she was dismissed from practice, we talked about doing another cycle or two -- pulsed steroid and four weeks of LDR starting one month after completion of the first cycle, and so on. The idea is to reduce the overall bulk with each cycle until it is down to a more acceptable and manageable level.

Would it have worked? Will I ever know? Since Dr. Belle is gone, I am now seeing Dr. O’Leary, who is open to the approach, but who is thinking of using it as maintenance at three month intervals. I’ll be seeing him in one month to see where my counts and nodes are and to discuss whether it can wait that long.

Dr. O’Leary, by the way, told me that he has had good luck with Rituxan and cyclophosphamide, which is the kissing cousin of good old chlorambucil. Most of us know by now that Dr. Hamblin has advocated R + CB as a useful treatment. It is interesting to note that I have stumbled across another doctor who is impressed by the results he gets with something very similar.

Certainly the question of “What next?” has been on my mind if and when LDR + LDMP ceases to hold the fort. Should I dip my toes in the chemo waters and add something that starts with a “C,” perhaps? In a future post I’ll discuss my thinking on where to go from here.

A LDR clinical trial note

There is a study of LDR underway at the NIH in Bethesda, MD. I understand they still have openings. If you’re interested in LDR, consider giving them a call. This link explains the trial and has contact information.

Low-dose Rituxan

As readers of this blog know by now, I am currently being treated with low-dose Rituxan, 20 mg/m2, every Monday, Wednesday, and Friday. The plan calls for this to continue until my white blood count is normalized or until I reach a plateau at which Rituxan no longer appears to be effective.

That “m2,” by the way, stands for per “meter squared,” which means the dosage is calibrated to my body surface area, a calculation involving my weight and height. When they hook the bag up to the IV pole, it actually contains 42 mg of rituximab. The standard dosage would be 375 mg/m2, which I have had often in the past, and which usually translated to about 750 - 780 mg per bag once my body mass was factored in. So, even a math dunce like me can see that it will take somewhere on the order of 18 infusions of low-dose Rituxan -- six weeks’ worth -- to equal one dose of standard-strength mouse juice. I’ve done five weeks so far.

If less can achieve the same or better results as more, there are obvious advantages to using less. These include reducing the possibility of creating disease resistance to the drug, fewer infusion reactions, and reduced chances of unwanted side effects such as delayed-onset neutropenia and potentially dangerous skin problems. Plus, depending upon how much you and your insurance are paying, it costs a lot less. The only loser is the manufacturer, Genentech.

On the other hand, it is important to remember that Rituxan is still Rituxan, and that its use as a single agent is not a panacea for chronic lymphocytic leukemia. Rituxan-induced remissions are not terribly deep nor durable. There is no reason to think that low-dose Rituxan remissions will last any longer than those at standard dose. As one doctor put it to me, “I have used low-dose rituximab a couple of times with no clear evidence of long term effect yet.”

Early word on low-dose Rituxan’s effectiveness

Still, if Rituxan is your poison, low-dose -- hereafter referred to as LDR -- may be worth considering. Here is the early data, some anecdotal, some from pilot studies:

One patient has posted her experience online, pointing out that her absolute lymphocyte count (ALC) dropped from 137k to 4.6k after eight weeks of LDR at 30 mg, given intravenously three times a week. She had used standard-dose Rituxan in the past.

A pilot study conducted by Dr. Ron Taylor (photo below) and other researchers at the University of Virginia, during which patients were given LDR by IV three times a week over four weeks, showed results ranging from stable disease to complete response (link at end of post, along with lots of other links). Not surprisingly, the complete responses were achieved in patients with the highest levels of CD20, and both were, it is interesting to note, 17p-deleted cases.

Another patient experience, detailed in a CLL Topics Alert, shows the more middling, “stable disease” end of LDR response -- the patient’s counts had been rising, almost doubled in the month before LDR began, and were stalled by LDR, but not reduced. After four weeks of subcutaneous injection of LDR, 20 mg three times a week, his ALC went from 44.7 to 46.0. Are his results a matter of his state of disease, his CD20 expression, or could the sub-Q method of administration be less effective than IV?

There is now a clinical trial underway, using a flat 20 mg of LDR, to help answer the question of LDR’s effectiveness in a larger cohort of patients than Dr. Taylor’s original pilot study. After all, the proof of any theory is in the patient pudding. The bottom line is not how elegant the theory, but how concrete the result. Your donations to CLL Topics are helping fund Dr. Taylor’s laboratory analysis of the trial data.

It should be noted that LDR can also be accompanied by nasty infusion reactions, so adequate premedication (usually Benadryl, Tagamet, Tylenol, and a steroid such as Solu-Cortef to reduce the inflammatory response) is a must. I know of one patient whose first infusion of 20 mg/m2 was a near-disaster, exacerbated by her doctor’s refusal to adequately premedicate her, which borders on malpractice. I do my LDR infusions with no premeds, but I have had standard-dose Rituxan 25 times in the past, so I know my limits and my tolerance. Even then, when the nurse ran the bag through a little too quickly one time, I got a chill and broke out in a sweat. LDR is not a license to forget about precautionary measures, and this also includes pre-treatment allopurinol and drinking lots of water, both of which help protect the kidneys from tumor lysis, which can happen when millions of cells die at once.

My experience with LDR

In my case, so far, LDR is bringing down the white count. As you may recall, I also had 72 mg of methylprednisolone daily for a week, which did an excellent job of debulking me, and which has been gradually tapered and is now at 4 mg a day. The importance of the steroid in my particular treatment cannot be overemphasized. Its addition to the protocol was triggered by the onset of autoimmune hemolytic anemia (AIHA). The hemolysis soon stopped, and my red counts have since been recovering, slowly but steadily.

One effect the steroid had was pushing CLL cells out of the spleen, nodes, and marrow, doubling my WBC to 364k at one point. Then, almost as quickly as it doubled, it dropped: to 271k after another week, and to 95k after another. LDR was only one factor here, I think. Another is the steroid itself, which has lympholytic (lymphocyte-killing) properties and very likely some synergy with Rituxan. Another significant factor was probably the ramping down and end of an infection that likely had precipitated the AIHA, and which had been driving my white count upward even before the AIHA set in. As any CLL patient who has gotten a cold knows, your count will go up and then down again when the cold is over. My supportive meds -- Bactrim, diflucan, augmentin, and acyclovir -- no doubt had something to do with the end of the infection.

Since my white count fell below 100k, the LDR has been dropping it steadily, from 95k to 81k three weeks ago, from 81k to 67k two weeks ago, and from 67k to 49k last week. At this rate, my count should be normalized in about three weeks. I say “should,” because as we go lower, we encounter a greater chance of reaching a plateau point, where the effectiveness of Rituxan ends and cells shorn of CD 20 begin. (Back in October, when I did standard-dose Rituxan three days a week, that plateau point was 22k, achieved after just five infusions.)

The bottom line today is that the steroid and LDR combination has worked better than I had hoped -- so far. That is the operative phrase: “so far.” The bulk is largely staying off and the count is going down. If I can get a normalized WBC and have reduced the bulk by a substantial amount, it will have been a successful treatment experience.

Whatever the end result -- whether I get as good as I’m hoping, or whether the counts plateau at a higher level -- the question comes up of how durable the result will be. The count is not everything; indeed, in a patient prone to bulkiness like me, it is less important than the nodes. Many patients who have used steroids to debulk report that the nodes come back within a month or so. It will be interesting to see if that happens in my case. The steroid dosage is now so low that it is doing little to hold back activity in the nodes. I have noticed a very minor uptick in one node on the side of my neck, and I get the impression that even as my counts continue to drop with LDR, the nodes will gradually begin their return.

So, I am left to wonder: Where will I be a month after treatment ends? Will the nodes be back to where they were before I started? Will they be a shadow of their former selves, indicating that the treatment has ramped the disease down to a good degree? How long might they be held in check before retreatment is needed?

As we all know in CLL, there are no easy answers, and different patients get different results with the same protocol. As the Romans used to say, experientia docet -- experience teaches.

Planning my encore

So, what do I do for an encore? It depends, to a great extent, on how my treatment plays out. But doing nothing until the disease gets as bad as it was before I started would not be wise. Those days are over. In my case, the “just let it go until you hit the wall” approach brings with it infections and AIHA, which are not worth the risk. Getting mashed against the wall like a bug on a windshield is messy and unpleasant, to say the least.

One option is to do another cycle, as it were, perhaps giving my body a month’s rest and then using a four-day course of steroids to debulk again, followed by more LDR. Chemotherapy often runs in cycles of up to six go-arounds of treatment. Would more cycles benefit me? Would I be able to gradually erode the disease through this method?

If it works, then I might be able to adopt a new “low-tox” route of disease maintenance: Repeat this process every so often -- say every four months -- to keep the disease in check. Add periodic IVIG to boost my immunity against infections. Take maintenance acyclovir, one 400 mg pill a day, to control the herpes virus (my titer for this was high recently). Acyclovir may also help against the Epstein-Barr virus, which I know I have floating around in my system, as I had infectious mononucleosis as a child. An EBV titer test has been taken, and the results are pending.

Another option, depending upon how deep a remission I get, is to consider following this treatment with Campath consolidation. Having unmutated, 11q-deleted CLL means the disease will return faster than it would in many other patients. Would using Campath at this point in my CLL career be worth the risks that accompany this important, highly immunosuppressive monoclonal antibody? I will be studying the ins and outs of Campath over the next month or two. Stay tuned.

What about other chemo drugs?

My thought on FCR is that it is still best saved for transplant conditioning, by which time it will probably be FCH (as in HuMax CD20) and likely a more effective regimen than FCR. While I have accepted the likelihood of having a transplant at some point, I see no survival advantage to doing it now, as opposed to putting it off for as long as reasonably possible. I am only 50 and have a ten-year window to accomplish the task. And so far, by the way, I have no signs of marrow failure.

Chlorambucil is another option, as is cyclophosphamide, which is considered to level the playing field for 11q patients. But I would have to investigate how much one of these drugs would meaningfully add to what I am already doing.

Meanwhile, back at low-dose Rituxan Ranch

The whole theory behind low-dose Rituxan has to do with CD20 shaving and complement, a subject that Dr. Taylor has been studying for several years. We all know that Rituxan is a man-made antibody that affixes itself to the CD20 “fingers” on B cells. In cancers such as non-Hodgkins lymphoma, where there is a lot of CD20 per B cell, Rituxan works pretty well. In CLL, there are fewer fingers, and therefore it is less effective. (HuMax CD20, Genmab’s new anti-CD20 monoclonal that will probably be on the market in a year or two, requires fewer finger to work well, and may be able to do in CLL what Rituxan does in NHL.)

Briefly, the idea behind CD20 shaving is this: One of the ways in which cell-kill is achieved when Rituxan is used is by complement-dependent cytotoxicity, or CDC. The body’s complement system provides a fundamental level of immunity, and includes those mighty cell-chomping macrophages, which look like something out of a science fiction movie (photo below). In a process called phagocytosis, those macrophages, along with granulocytes, kill “invaders” such as Rituxan-tagged B cells (and innocent little red cells, when things go haywire in AIHA). But they become overwhelmed by the sheer number of Rituxan-B cell complexes when a lot of Rituxan is used (Taylor et al are still trying to define “a lot,” but is appears to be somewhere above 30 mg, definitely above 60 mg, and therefore includes standard-dose Rituxan). At a certain point, rather than killing the cells, the cells are sent to the liver, where they are shorn of their Rituxan-B cell complexes but not killed. In other words, the body has taken a shortcut to solving the problem. Et voila -- what returns to the bloodstream is a B CLL cell, minus its CD20 and any Rituxan that was attached to it. You have now officially shot yourself in the foot, or somewhere worse. Yes, CD20 may grown back over time, but there is no doubt that this process is a setback in treatment that is better off avoided. You don’t want to end up feeling like the cat in the photo at the end of this post.

Complementary medicine

Beyond this, there is evidence that the massive cell-kill process initiated when Rituxan is used also depletes complement. It recovers, but not immediately, rendering diminishing results in the interim. Early in his research, Taylor looked at this end of the problem and asked: What if we give the patient more complement? In a 2002 abstract, Taylor and colleagues concluded: “We suggest that if an anti-tumor mAb such as Rituxan requires robust Complement (C) activation for therapeutic efficacy, then insuring an adequate level of C activity in a patient, by supplementation with either fresh plasma or a purified C component such as C2, may provide an important approach for improving the therapeutic efficacy of a C-fixing mAb.”

This sounds logical, and an abstract presented at ASH in 2005 by Israeli doctors showed that this worked in one patient: a woman who had been through the chemo mill, including fludarabine and cyclophosphamide as well as Rituxan, and who was barely responsive to therapy anymore. Her doctors gave her two units of fresh-frozen plasma followed by 400 mg/m2 of Rituxan on day one, and the same amount of plasma followed by 275 mg/m2 of Rituxan on day two. They described her response as “dramatic,” and this included “marked reduction of lymphadenopathy” and resolution of other symptoms.

“To the best of our knowledge,” the doctors concluded, “this is the first description of a case where successful induction of dramatic and rapid improvement of both clinical and laboratory parameters in a patient with advanced CLL previously resistant to Rituxan-containing chemo-immunotherapy was achieved by combining Rituxan therapy with fresh frozen plasma as a source for complement. This observation has to be verified in additional patients in order to confirm the approach of potentiation of Rituxan effect by providing increased amount of complement in order to augment CDC.”

So, why not go this route? Well, I tried to get my second hem/onc, Dr. Chopin, interested in it back in 2005, and she looked at me like a deer caught in the headlights. The fact is that it is impractical and experimental. Using lower-doses of Rituxan, so that complement does not become overwhelmed in the first place, is far more practical, as well as more cost effective.

Non-standard standards

How did 375 mg/m2 get to be the standard dose for Rituxan in CLL? There appears to be some question about this. One suggestion is that this was an arbitrary dose, determined by how much was on hand in an early study and how many patients needed to be treated. Another explanation is that it is based on a pivotal trial of Rituxan in patients with relapsed indolent lymphomas such as low-grade NHL. In this trial, the results published in 1998 by McLaughlin et al of MD Anderson, dosages of 375 mg/m2 once weekly for four weeks were used. This formed the basis for the use of 375 mg/m2 in the 2001 CLL study by Byrd et al -- it is directly cited -- in which patients were given Rituxan three times a week. This was in an effort to make up for the difference in effectiveness, as it were, between CD20 expression in indolent lymphomas and CLL. (Dr. Byrd still uses this protocol, and this is the one I tried last October until a plateau was reached, so the results in my case were rather disappointing.)

The larger point is this: There may not always be a truly logical reason behind the dose-selection of drugs. If the story about arbitrary dosage of Rituxan is true, that certainly raises a red flag. Even if the 375 mg/m2 is based on results in NHL, that may not hold water as a logical step in CLL. Low-dose Rituxan is no less logical than any of the above, and may be supported by better theory. So if it seems “weird,” it is certainly no less “weird” than the “standard.”

Another example is FCR therapy. It appears from reading CLL Topics that the FCR “lite” protocol currently in trial at the University of Pittsburgh may be every bit as effective as the regular-strength FCR protocol pioneered at MD Anderson. One would like to be a fly on the wall at meetings where dosages are determined. Is there a dartboard in the room? Do our famed researchers use “paper, scissors, rock” to decide how much fludarabine to give?

I’d like to think, of course, that the soundest of science is backing these choices, but I have a feeling that educated guesswork is every bit as common. However dosages are determined, the bottom line for us patients could not be more important. Thousands of us CLLers may have been unnecessarily overusing Rituxan for years, until a light bulb went off in Ron Taylor’s head. We shall see, of course, how brightly it shines and where it leads us.

Reading up on LDR

For those who want to examine LDR in more detail, here are some useful links that I have assembled.

Dr. Taylor does a nice job of explaining CD20 shaving in layman’s terms in a short piece he wrote for the UK CLL Support Association entitled Shaving and Rituximab: Targeting the Sharks. Chaya Venkat of CLL Topics does her usual excellent job of translating medicalese into English in the article CD 20 Shaving with Rituxan. An earlier article of Chaya’s, Role of Complement in Rituxan Therapy, is also worth reading and contains the complete abstract of Dr. Taylor’s early work suggesting that the addition of complement to Rituxan may be useful.

Dr. Taylor and colleagues have published three abstracts you might want to read. They are:

Pilot Study of Thrice-Weekly Low-Dose Rituximab (RTX) in Chronic Lymphocytic Leukemia (CLL): Decreased CD20 Loss Via "Shaving" and a Novel Strategy for Enhanced Therapeutic Targeting

A Pilot Study of Thrice-Weekly Low Dose Rituximab (RTX) in the Treatment of Chronic Lymphocytic Leukemia (CLL) Suggests Enhanced Therapeutic Targeting Compared to Standard Dose Regimens

Thrice-Weekly Low-Dose Rituximab Decreases CD20 Loss via Shaving and Promotes Enhanced Targeting in Chronic Lymphocytic Leukemia

Here is the clinical trial now underway at the NIH, which is apparently still recruiting patients, so those of you with a hankering to visit Bethesda, MD may wish to consider it:

Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia

The Israeli abstract -- Successful Induction of a Rapid Improvement of Both Clinical and Laboratory Parameters in a Patient with Advanced CLL by Combining Rituximab with Fresh Frozen Plasma as a Source for Complement. A Novel Therapeutic Approach? -- is only available online by logging into ASH and looking up their 2005 conference. Registration is free and it is abstract #5030.

Debulking: the amazing photographic evidence

I mentioned recently the rather astonishing debulking effect that methylprednisolone -- being used to treat autoimmune hemolytic anemia -- has had on my chronic lymphocytic leukemia. Sometimes a picture is worth a thousand words, so I am posting two pictures today in lieu of writing 2,000 words.

The top photo is me on February 7, before the AIHA came calling and any treatment was done. Someone was kind enough to say that my thick neck made it look like I had been working out, but the only workout was being done by the CLL, which was ever expanding itself into lymph node masses.

The second photo was taken March 25, a little more than a week after starting treatment with 72 mg of methylprednisolone for the AIHA (and also 20 mg/m2 of low-dose Rituxan three times a week). Who is that man with the neck?

Now, imagine that sort of lymph node impaction throughout my abdomen -- I have no doubt that the bothersome pelvic nodes I have written about in the past were in a similar mass -- and you know why I slimmed down there, too, and no longer need my "maternity clothes." Altogether, I have lost 22 pounds since starting the steroids, which are now tapered to 16 mg daily. (As to the AIHA, I am doing OK but the red counts are still not normalized.)

I hope these photos show what unmutated, 11q-deleted clones of "the good cancer" can do. Often we patients get used to a slow change in our appearance and forget what we looked like before the lymph nodes began to swell. And while this shows what the CLL visibly did, another big part of the story is what it did that I couldn't see -- compromised my immune function, allowing something, probably an infection, to trigger the AIHA.

By the way, I made this note to myself on the third day of methylprednisolone therapy: "After two days of steroid, nodes reduced to about the least since initial (Rituxan) treatment three years ago. Six pounds lost." In other words, the debulking occurred substantially within the first few days of steroid therapy. Today, only two palpable, almond-sized lymph nodes remain in the fleshy area under my jawline, both vastly reduced from before.

The challenge ahead, after recovering fully from the AIHA, is to maintain my slimmer physique by good diet and exercise and to keep the CLL at bay. Seeing the massive bulk that was built up in me, and coping with the hidden consequences of the disease running amok which suddenly came to the fore as AIHA, has caused me to do a little thinking about the possibility of using something a little stronger to solidify my remission.

In the meantime, here are the photos, before and after: