Not a rash decision

Round six of my bendamustine and rituximab therapy has been delayed on account of a mysterious rash. 

A few months ago I noticed a half dozen or so raised spots that I assumed were bug bites and thought nothing more about it. It's possible that they were bug bites, or it's possible that they were the start of an allergic response to one or both of the drugs I've been taking.

During the past month, and especially in the past couple of weeks, a rash both similar and different has spread. Some are raised, some are flat, and the flat ones are both circular and asymmetrical. I've got these in at least two dozen places, including the head, arms, chest, and legs. There's no particular pattern; like spring flowers, they're busting out all over.

On Wednesday I saw my dermatologist, who took two biopsies (results pending) and suggested that the rash was either a reaction to the chemotherpy or lymphocytic infiltration of the skin.

The latter is a new one on me, but apparently it can happen. On Friday I saw my oncologist, Dr. Droll, who said he doubts it's that. One reason is that my CLL is in pretty good remission after five rounds of B & R; the other is that the pattern of my rash does not look like lymphocytic infiltration that he has seen.

Dr. Droll thinks this could be a reaction to one of the drugs, probably Rituxan, or else a general immune dysfunction. Last year, when I was on Revlimid, I began to develop rashes with greater frequency in response to things that previously had not bothered me, such as experiencing the pollens in a new location or sweating in the Arizona heat. It seemed that Revlimid had amped up my immune response; my instinct tells me that immune "over-response" to something -- possibly Rituxan -- is what's going on here.

Both Dr. Droll and I shared the instinct that going forward with my sixth and final round of chemo next week would be a, um, rash decision, possibly adding fuel to the fire.

We're going to wait for the biopsy results. He also suggested that I might want to do the dreaded four-day pulsed dexamethasone regimen again, as that could tamp down any overboard immune response that might be happening. I'm probably going to give it a try, as the rash spots are only getting more numerous. 

I'm treating them topically with triamcinolone (corticosteroid) cream. The dermatologist said this will relieve symptoms (some of the spots are itchy sometimes) although it may not make them go away. Which is another reason for trying the pulsed steroids, to try to shut the whole process down.

The long-term plan is to go ahead with round six of B & R when the rash is under control, and to consider doing it without the R.

Meanwhile, round five was fairly uneventful, but surrounded by uncertainty about a mysterious jump in my blood calcium levels. Hypercalcemia can be scary, as it is often associated with end-stage cancer or a new cancer; luckily, the story has a happy ending and an unlikely culprit. I'll write about it soon.

Bendamustine & rituximab, round four

My latest round of B-R ended almost three weeks ago and was pretty uneventful as these things go. Last week's blood work put my hemoglobin at 11.3, platelets at 205. My absolute lymphocyte count is 0.4, which the lab report describes as "low." 

The infusions were uneventful, and I had only mild nausea for one day. The most noticeable side effect was fatigue that lasted longer than usual. It dragged on for a couple of weeks this time; Dr. Droll says this is because the longer you do chemo, the more cumulative the effect.

Lymph nodes continue to reduce. I now weigh 170, which I have not weighed since sometime in the 1980s. I've lost about 25 pounds since starting B-R. I think most of this can be attributed to loss of lymph node and associated weight. I don't expect to achieve complete clearance of the nodes with B-R -- unless I do 10 rounds, which I won't be; the protocol stops at six. But it will knock the nodes back to, let's say, 2006 levels. I've made an appointment with CLL expert Dr. Thomas Kipps in January to discuss ways to protect and extend the remission.

Speaking of protecting and extending, tomorrow is election day. If worse comes to worse and I should need a stem cell transplant, which my insurance doesn't cover, there are two futures awaiting me.

If Obama wins, I will be able to choose a plan under the health care exchanges set to come online about a year from now; I won't be rejected because of my pre-existing condition, and I should be able to find an affordable plan that covers transplants and is superior in many other ways to the one I am stuck with now.

If Romney wins and repeals the Affordable Care Act, I guess I'll have to take the candidate's advice and go to the emergency room, where I can demand a stem cell transplant and then be laughed out the door.

You know how I'm voting; I hope you'll vote with me for the the president, who represents the better angels of our nature.

Bendamustine & rituximab, round three

My third go-around with bendamustine (Treanda) and rituximab is over, with some notably different reactions than before.

The main event involved a 14-hour bout of diarrhea, which began the night of the second bendamustine infusion. I will spare you the details. But it is appropriate here that I say "Thank you" to the makers of Imodium, which I now regard as one of the Ten Wonders of the Modern World, ranking somewhere after the automobile and somewhere before air conditioning.  

(FYI, according to the chemo nurses, you can take an Imodium pill every two hours, despite what it says on the box. That schedule proved quite effective.)

Otherwise, Round Three went off without the infusion reaction to Rituxan that characterized the first two rounds, probably because I was premedicated with enough Benadryl, Demerol and Solu-Medrol to bring down a rabid tiger.

Round Three brought some noticeable reduction in abdominal lymph nodes, which I had been hoping to see as the treatments progressed. I am now one loop tighter on my belt. I still have a long way to go in the abdominal nodes department, but this is encouraging. Three more cycles of B&R await me; I am guessing that I won't get a complete remission but I may get as much of a remission as I could have reasonably hoped for.

Blood counts remain decent, with hemoglobin in the 10s and platelets around 110. Dr. Droll says the numbers should go up as the treatment progresses. My absolute lymphocyte count remains laughably low.  (UPDATE: As of my Oct. 1 CBC, ALC is 0.9, hemoglobin has risen to 11, and platelets are at 204, the highest they have been in years.)

The post-chemo fatigue and nausea that I wrote about following Round Two were there again, but in milder form. It's Monday, and the last infusion was Wednesday of last week, and I am feeling normal again, or as normal as I get.

Endless war

Today is the ninth anniversary of my diagnosis with chronic lymphocytic leukemia, after which I will enter my tenth year of fighting this thing.

The date September 3 occupies the same place in my memory as September 11, November 22, and December 7. In other words, it is a date that lives in infamy.

I have some random thoughts today, as I do every time September 3 rolls around.

One is that I am living in what the late CLL expert Dr. Terry Hamblin would have regarded as my end times. People with my type of CLL (unmutated, 11q-deleted, at least up until recently) live about eight to twelve years after diagnosis, he once told me. He had hundreds, if not thousands, of case histories to back up that assertion.

But he told me this back in 2006 or 2007, and fortunately a lot has changed in CLL very quickly. I have been able to take advantage of two new treatments, lenalidomide (Revlimid) and now bendamustine (Treanda). The horizon looks a little bright, what with the kinase inhibitor trials that seem to be keeping CLL in check, as well as the killer T-cell technology that is being developed to, just perhaps, put an end to the disease once and for all. There’s more stuff out there; I can’t keep track of it all. But I do believe that someday in the not-too-distant future, maybe in another nine years, CLL as we know it today will be a highly controllable beast. (And I have no doubt that within the lifetimes of some readers of this blog, it will basically become a curable condition.)

I just have to get from here to there and beat Dr. Hamblin’s odds. There are ways to try to do this. One is to make the best decisions possible, which is never easy. I've made my choices, and unless there is an alternate universe somewhere with another me who chose a different course, there's no way of knowing if I have made the best choices. There is a reason why I keep this quote from Vaclav Havel on the right side of this page: "Hope is not the conviction that something will turn out well, but the certainty that something makes sense, regardless of how it turns out." 

A second factor is the pace of research and development, the degree to which progress in treatment is made, both through dogged determination and strokes of good fortune. In this department, things are moving about as fast as can be hoped.

A third factor is the ultimate one, in my view: Luck.

For all the problems with our medical system, I am lucky to live in the United States, where most of the CLL research and clinical trials of import take place. I am not so lucky to be saddled with bad insurance, but there are ways to get past some of those limitations if one is willing to dig deep enough and be persistent enough. Still, the re-election of Barack Obama may have a direct impact on my life span. The survivability of the Affordable Care Act, which would allow me to purchase much better private insurance in 2014, is a personal thing to me.

More than that, luck has a lot to do with how the disease progresses, what course it takes. We CLLers live forever with the prospect of a shoe dropping somewhere, bringing with it a new and unwelcome challenge. I’ve had my problems this past year, but the current bendamustine-rituximab treatments appear to be giving me a new lease on life, as it were. Where things will be with me in three, six, nine years, I cannot know. I do know that the disease rarely gets better the longer you have it; I also know that new treatments are changing the game.

Playing the game is an inescapable fact of life for those with a chronic disease. After nine long years I feel like a veteran of what Dr. Hamblin once likened to a war of attrition. Another CLL expert, Dr. John Byrd, told me in 2006 that CLL is a long journey.

May yours – and mine – be so long as to see the day when we can live our lives without it.

Holy bendamustine, Batman! (B-R round two)

I have finished the second of my six bendamustine-rituximab treatments, and this time the regimen came with some "Kapow" and a little "Bam."

To guard against tumor lysis, my first treatment involved only two-thirds of the standard dose of bendamustine (aka Treanda); this time I had the full 100mg/m2. My reaction was significantly more intense than the easy-breezy first time around.

The bendamustine was administered last Tuesday and Wednesday. Tuesday also included the Rituxan, which brought forth infusion reactions unlike any I have had before. The ill effects of the bendamustine -- fatigue and low-level nausea -- didn't set in until Thursday night, and have only really abated today.

More on that later. First, there is good news to report. The higher dose has done a much more noticeable job on the nodes, almost returning my neck to its natural swanlike appearance, and reducing a large mass in the abdomen to a reasonable degree. I still have a long way to go with the nodes, but if this keeps up, I will have made significant progress by the time I'm through.

One question is how long the nodes will stay at their current size. Last time around, they began to bounce back in the week before my second treatment. By the time I sat down in the infusion chair, most of the progress that had been made thanks to the first round had been erased.

This is not a good sign, and it indicates how fast my disease is prone to grow. But my reaction to round two, with a much more noticeable node reduction than round one, makes me cautiously optimistic that the effort will hold this time. Which, fingers crossed, means round three should see an overall further reduction in the nodes.

I am hopeful that the cumulative effect of the treatments will largely shut down the CLL factory in the marrow as well as reducing it in the nodes, creating a smaller, more easily manageable disease.

A FISH story

For some time I have wondered if my disease has turned more aggressive, or whether it has reached a critical mass, like a snowball rolling downhill, gathering size until it gets so big that it is difficult to stop.

A first step was to get a new FISH test, which I did in April. Would there be a 17p deletion there, indicating more aggressive disease?

The results were a little surprising. My first FISH test, back in 2004, showed a "normal" karyotype, which meant the chromosomal damage was of a nature not probed for on the test. In 2006, the FISH came back positive for the 11q deletion on 24% of cells examined, not good news. 2007's FISH showed 11q in 36% of cells. 2008's FISH showed 11q on 53% of cells. In 2009, 11q was noted on 31% of cells examined. (Why the dip? Who knows? But it didn't change the basic picture: an 11q deletion that appeared to have increased in the number of cells over time. By the way, the deletion always showed up on one arm of the chromosome only, which was of some comfort, as it meant I still had some ATM function, ostensibly.)

2010 and 2011, the Revlimid years, were FISH-free as the disease was under control for most of the time. Then in April of this year came an interesting twist: the 11q was down to 8% and a new deletion, 13q, again on one arm of the chromosome, was found on 30% of cells examined.

That FISH test was from the peripheral blood. In July, I had a bone marrow biopsy, which showed 90% involvement by CLL. A FISH was performed on that sample. It showed no 11q deletion at all, and a 13q deletion on 42% of cells.

So, what does all this mean? It appears my 11q clones are in decline, which is good news. (Why that is, again, who knows? It appears to fly in the face of conventional wisdom. My hunch, which is a completely wild guess, is that my Revlimid treatments had something to do with it.)

The April FISH showed a double deletion (11q and 13q), which is not good news. And while 13q is considered the most benign of the deletions, there are a couple of flavors of 13q. One indicates more aggressive disease; the tests I had did not go beyond the basic probe, indicating a deletion of one arm of 13q14.3.

I don't think the handoff from 11q to 13q indicates an improvement in my disease. But this is about the best change I can hope for; it would seem to indicate that the disease is probably not more aggressive by nature than it was before.

So I am basically subscribing to the snowball theory, and only time will tell if I am right. Another point I am compelled to make: FISH tests are all well and good, but shy of showing a 17p deletion, the most important factor in deciding to treat the disease is your clinical condition.

On the way from Calais

The last time I recall feeling as nauseous as I did post-bendamustine was many years ago on a boat from France to England. This was in the pre-Chunnel days. I grew whiter and whiter as the white cliffs of Dover approached, barely managing to contain my nausea with each bumping wave.

The nausea that set in last Friday never got to the barfing point, but it was uncontrollable with ondansetron (Zofran) tablets, which worked less well than Pepto-Bismol. To keep my kidneys flushing the dead CLL cells through, I needed to be drinking lots of water, and water is the last thing a sensitive stomach can tolerate. If I never see another can of Blue Sky New Century Cola again, it will be too soon. Needless to say, food was also rather unwelcome; I managed to lose some noticeable weight since nothing was appealing, although my stomach eventually discovered that macaroni and cheese was tolerable.

The fatigue was also way out of the ordinary. I would sleep 14 hours, on and off, and wake up tired. Today, Wednesday, is the first day that feels normal, both in terms of fatigue and nausea.

Although it sometimes felt as if my hemoglobin had taken a hit -- benadamustine can lower hemoglobin temporarily in about 90% of cases -- it turned out that wasn't the case. Comparing some numbers from the day before I started the second round to six days after I finished it: hemoglobin 10.8 before, 10.5 after; platelets 147 before, 138 after; absolute neutrophils 4.9 before, 5.4 after (as in the first round, I had a Neulasta shot on the day after completing treatment). The only dramatic change was in absolute lymphoctye count: 13.6 before, 2.1 after. I don't think my ALC has ever been so low.

UPDATE: My blood work from two weeks after treatment showed signs of decline in hemoglobin (down to 9.3) and platelets (110). Absolute lymphocyte count was 1.4, a new record low.

The rigors, minus the mortis

Last Tuesday's plan was to infuse the rituximab, then the bendamustine. My reaction to rituximab, a drug I have had countless times, was surprising. I was given prophylactic Benadryl and Solu-Medrol and expected pretty smooth sailing. About 15 minutes in, my face turned red and I felt some shortness of breath. This eventually abated, thanks to stopping the treatment, accompanied by some oxygen.

About 10 minutes after the infusion resumed, I experienced what the chemo nurses called "the rigors." This symptom was appropriately named, as it involved rigorous uncontrollable shaking. You can wear out your thigh muscles fast when this happens. Imagine having "the chills" but it's all coming from an internal place, so it doesn't matter how many blankets they pile on you, you still can't get warm. I think the rigors lasted about 15 or 20 minutes, during which time I found myself wondering whether this was what the passengers on the Titanic went through when they fell into the icy Atlantic. It finally abated, thanks to some more Solu-Medrol and Benadryl, as well as some Demerol. The Rituxan was stopped and I was given the bendamustine; reversing the order sometimes helps in such cases. Sure enough, when the Rituxan infusion was resumed later, it was completed without incident.

Why would someone who had managed to accommodate Rituxan for years with minor reactions, if any, suddenly develop these sort of symptoms? Again, who knows? With groundless abandon, I theorize that Revlimid changed something in my immune function. The Revlimid put an end to my autoimmune hemolytic anemia, but also led to a more hair-trigger allergy response in terms of skin rashes. Perhaps it also created a microenvironment less friendly to Rituxan.

My next sojourn in the chair is scheduled for mid-September. Keeping my eyes on the prize, I look forward to making more progress against the disease. But I'm not counting on an easy ride, and I will lay in a supply of macaroni and cheese, just in case.

Off to a good start with bendamustine and rituximab

I have just completed cycle one of six in my bendamustine and rituximab treatment and things are going well.

These drugs are also known as Treanda and Rituxan. "Treanda" sounds like a girl's name from the Maury show, but to my mind it is cyclophosphamide's big brother, an alkalyting agent with a powerful kick. Rituxan, of course, is the ubiquitous anti-CD 20 antibody that we CLLers have been using alone and in combination with chemotherapy for several years.

I'm pleased to report that the treatment is showing the signs of effectiveness that I had hoped for, with only a few bumps in the road. The best news is that it cleaned out my bone marrow enough on the first go-around that I am making more red blood cells and am getting out of the anemia rut that came with marrow impaction. I entered treatment with a hemoglobin of 7.8 and less than a week later I'm at 11.4.

Not a lot has been written about patient experiences with BR in chronic lymphocytic leukemia, so I will describe mine in some detail. Remember that this is an anecdotal report, and that your mileage will vary; but perhaps I'll be able to give you some idea of what BR is like, and some of the things to consider and watch out for.

My first thought is that how you manage treatment is important. This should be a no-brainer, but people with no brains are dishing out chemotherapy every day, sometimes to the great disadvantage of the patient.

Going in with bulky disease and a bone marrow packed with CLL, my oncologist, Dr. Droll, felt it was best to start treatment at a lower dose and to do so in the hospital. I spent three nights at the lovely Banner Baywood, the name of which evokes a resort hotel (which no doubt would have been a lot cheaper), in Mesa, AZ. I was monitored for tumor lysis syndrome, which can occur when there is so much cell-kill that the kidneys are damaged. The hospital also kept track of my hemoglobin; bendamustine is known to reduce hemoglobin temporarily in about 90% of cases; it turned out that I needed four units of blood.

The photos I've posted show the room that was my home at Banner Baywood, which is a short walk from Dr. Droll's office. I was on the sixth floor cancer ward in a private room, since I was receiving chemotherapy and sharing a room could have, in theory, exposed the other patient to dangerous drugs The nurses could not have been nicer, and Marilyn stayed by my side the whole time, sleeping in a fold-out chair that reminded us of an uncomfortable cuchette that we once endured on an Italian train. I urged her to consider checking into a hotel, but love is stronger than a comfy mattress.

It helps to have a good caregiver with you, someone to watch you for infusion reactions that you may not be aware of, someone to keep an eye on what is being done, to get questions answered, to be there during the uncertain or scary times, and to raid the refrigerator at night when you want an egg salad sandwich.

Tuesday, July 24th began with a call from the hospital at 9:40 a.m.; a bed was ready. We pulled ourselves together and drove the two-and-a-half-hours to Mesa, a city east of Phoenix. We arrived at about 2:30 p.m. I was weighed, my height was recorded, and this was duly noted on the dry-erase board that serves as the information center in the hospital room.

I also had my vitals taken -- blood pressure, pulse, oxygen level, and temperature -- for the first of what seemed to be about six thousand times. One thing you learn quickly in the hospital is that you're not going to get a lot of uninterrupted sleep; there's always someone doing a vitals check, or drawing blood, or one of several other things that can leave you feeling very unrested. One morning between 6 a.m. and 9 a.m. we counted twelve visitors, including the chaplain, the "patient navigator" from the American Cancer Society, and, of course, the hospitalist. The hospitalist is the doctor who is in charge of the ward, although he had nothing to do with my treatment. I call him Dr. Ka-Ching, because I will no doubt owe him at least $500 for the 45 seconds he spent with me each day.

My first set of vitals put my blood pressure at 134/68, heart rate of 97, temperature of 36.8 Celsius (98.6), oxygen level of 95%. What's interesting is that once I started chemo these numbers immediately improved, and stayed improved, throughout my stay. My systolic pressure would typically be about 115, and the diastolic remained in the 60s and 70s. Oxygen level went up a tick, heart rate dropped into the 70s.

Dr. Droll came by and said he was lowering the bendamustine dose by one-third. Instead of 100 mg/m2, I received 65 mg/m2, which was modified by the hospital pharmacist to 125 mg per infusion. The doctor also said he wanted me to stop by the office on Friday for a Neulasta shot, which is a good precaution when using bendamustine. B can clobber the neutrophils, leaving the patient subject to all sorts of bad reactions that can put you in the ER.

To guard against tumor lysis, I was advised to continue on allopurinol (300 mg/day), which I had been taking for four days. (Please note that there can be some skin issues when allopurinol is used with bendamustine. I haven't had any problems, but it's something to watch for. According to an FDA warning letter to the drug's maker, Cephalon, "Allopurinol has also been used during the beginning of TREANDA therapy. However, there may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly.")

I was also advised to stay well hydrated, which would keep dead cells moving through the kidneys. I was put on a saline solution, dispensed at 150 mg per hour, with some variations in speed over the next few days, and my urine was monitored. I was asked to pee into a plastic urinal with numbers on the side, and the nurses duly recorded the volume to make sure that my output equaled my intake. Everything I drank was monitored as well.

Dr. Droll exited stage left, announcing that he was going on vacation, and that one of his partners would visit me each morning.

Rituximab, the big unknown, was infused first. I have lost track of how many infusions of Rituxan I have had since I first used it in 2004. I am guessing about two to three dozen, give or take a few. One of the big questions going in was whether R would work on me at all, as it had, over time, become less and less effective. But I had not had it in 2 1/2 years, and research shows that in the presence of bendamustine it can work in Rituxan-refractory patients.

I'm still waiting for the lobster.

Premeds consisted of 25 mg of Benadryl and two Tylenol. No steroids were given, which I questioned, since in all previous instances I had been given 125 mg of hydrocortisone or Solu-Medrol.  The chemo nurse said that steroids were in Dr. Droll's orders "if needed" and that at Banner Baywood it was routine practice not to give steroids as prophylaxis before infusing rituximab.

"What strange corner of Mesa have I stumbled onto?," I wondered. But I figured I'd go along with the program, when in Rome and all, having never had a really bad reaction to Rituxan. Sometimes during the first infusion, about 40 minutes in, I would get a flushed face or some tightness in the throat. A couple of times this led to a temporary halt in the infusion, and/or giving more steroids. Then things would calm down and be uneventful the rest of the way.

Sure enough, about 40 minutes in, I began to react. This involved profuse sweating and shortness of breath, and I do mean shortness of breath. My blood oxygen level dropped into the high 80s. Not since I almost drowned in a swimming pool as a child have I felt that close to being unable to breathe. It was scary. I was hooked up to oxygen and the nurse proceeded to go about getting some steroids in me. I was given 40 mg of Solu-Medrol, the maximum that Dr. Droll's orders indicated. I needed more, and this took a little while to arrange, since Dr. Droll's Partner had to be reached by phone to agree to exceed the dose set by Dr. Droll, which he did. Another 100 mg of Solu-Medrol was administered and it worked.

Suffice it to say that Dr. Droll and I are going to have a conversation about Rituxan premeds and that at least two chemo nurses at Banner Baywood are now aware that CLL patients ought to be given steroids as prophylaxis when Rituxan is used. 

The good news is that Rituxan showed signs of working almost immediately. In the old days, when I used it as a single agent, there would be some tumor flare in my neck after a couple of hours. The area with the nodes would also turn a little red. The idea is that the body was responding to an area where there was now an antibody, cell-kill was ensuing, and this was part of the process by which the nodes were reduced. In later infusions, when I wasn't sure that Rituxan was working, this reaction would be absent. But sure enough, it was happening again, and I had not yet had bendamustine, so it was not the product of that drug's influence. Call it chance, call it luck, but it was a very good sign.

Bendamustine was started at 12:47 a.m. In the hospital they can give chemo 24/7, and they do. The Rituxan had taken forever, from 5:20 p.m. to 11:30 p.m. Premeds for the B consisted of 12 mg of dexamethasone and 24 mg of ondansetron (generic for Zofran, an anti-nausea drug), as well as 40 mg of Lovenox to prevent clotting.

The B was started at 10 ml/hour and was raised incrementally to 400 ml/hour, and it took an hour and a half to infuse. The chemo nurse kept track of the vein in my left arm into which all of this was pouring; I have never had a port, and I am evidently some sort of God when it comes to having good veins, but she wanted to make sure the vein did not blow, which can happen with rapid bendamustine infusions.

All went well. She may as well have been infusing me with water for all the reaction I had, which was no reaction at all. After the Rituxan it was anticlimactic, and I had had enough drama for one evening.

There was, however, to be no rest for the weary. I entered the hospital with a hemoglobin of 7.8 and Dr. Droll's orders called for a red blood cell transfusion if the hemoglobin was below 8. So I was given two units of blood, taking about three-and-a-half hours each.

The blood was irradiated, CMV negative, with leukocytes removed, so it was about as pure as it was possible to get. I had no infusion reactions and did finally manage to get some sleep, although the entire process was not finished until about 9:30 a.m. the next day.

I should note that these days, at least at Banner Baywood, the patient armband has a UPC code; nurses use a scanner on it that verifies who a drug is for (and no doubt adds it to the bill.) This also tells them if a drug is contraindicated with another that the patient has been given. A separate armband is used for blood products. When blood was transfused, two nurses would come in and, in addition to the scan, repeat my name, date of birth, blood type, and so on to verify that the right person was getting the right stuff. I appreciated this attention to detail. There is enough to worry about when doing chemo without having to worry that you're being given something by mistake.


Day Two involved the second and last bendamustine infusion as well as two more units of blood. All were uneventful in terms of infusion reactions.

The blood was ordered because my hemoglobin, which had been raised by 1.6 points thanks to the first two units, had again slipped below 8. Given that bendamustine takes a toll on hemoglobin in 89% of cases, it was not surprising that the number didn't hold. (My platelets were taking a hit as well, having been 127 upon admission and 71 on discharge. This drop occurs in 77%-86% of cases. Absolute neutrophils actually increased, which is something of an anomaly, from 1.82 to 2.42. Neutropenia is reported in 75%-86% of cases.)

Dr. Droll's Partner stopped by with another theory; perhaps I was being so well hydrated to avoid tumor lysis that it was causing the hemoglobin number to drop. It is true that if you want to increase your hemoglobin on a CBC, going into the test dehydrated will help. So he cut the flow rate of the saline solution to 60 ml/hour and said he wanted me to stay in the hospital one more day to monitor the situation. This prospect was not greeted with huzzahs by me or my loved one -- the chemo nurse was amused to learn that a sweet-looking lady can curse like a sailor -- but we understood the reasoning.

Sure enough, the next morning, my hemoglobin was 9.0 and I was a free man.

I feel significantly better following the chemo. That's the bottom line, after all. I have a great deal more energy, thanks in part to that 11.4 hemoglobin. I feel as if I have my life back; I can do things around the house again, run errands and not get winded, and so on. I'm not ready to run any marathons, but things feel more normal than they have in some time. Perhaps the CLL was taking an overall toll on my system that helped account for my low energy on top of the low hemoglobin; putting it in check has done more in a short time than I expected. It is interesting that my heart rate dropped so dramatically -- from the 90s to the 70s -- after therapy.

My major challenges are the lymph nodes and bone marrow. There are five more cycles to go and I am optimistic that I will have a significant reduction in nodes. Odds are very good that I am among the bulkier CLL patients ever to use BR. My nodes tend to be smaller, but they fuse together in clumps when left unchecked. Treatment then breaks them up. Already the neck nodes are noticeably and significantly reduced. The masses that were under my arms are now individual, smaller nodes, though still significant. My abdomen has slimmed down and I look a mere seven months pregnant instead of nine. I have lost about five pounds, much of which is probably lymph node weight.

My white blood count, which is really the least of my problems, dropped from 71.7 to 12.1 on discharge and 8.2 four days after discharge. Platelets have begun to recover as well, now at 112, up from 71 at discharge. The Neulasta bumped absolute neutrophils up to 4.7. The hemoglobin, which was 9.0 after the last two units of blood, is at 11.4 four days later. That is the highest it has been since last December and I am surprised, in a good way, at the rapid turnaround.

I managed to avoid tumor lysis syndrome as well. I picked up a few things from the nurses on what they look for. In extreme cases they see signs of mental confusion, but I was no more confused than I usually am. They also pay attention to creatinine levels, uric acid, and electrolytes such as potassium, magnesium, calcium, and phosphorous. At one point my magnesium and phosphorous were a little high and calcium a little low, but nothing to worry about. The other numbers remained within the normal reference range. 

One thing I noticed on the tests that has been little-discussed is a rise in blood glucose levels. Back when I used to do RCD -- rituximab, cyclophosphamide, and dexamethasone -- to combat autoimmune hemolytic anemia, my glucose levels would rise. My oncologist at the time, Dr. Meng, said this was mainly due to the cyclophosphamide, which can cause hyperglycemia (although I am sure the steroids contributed as well).

Diabetes is not an issue for me and in a fasting state I test out at normal glucose levels. I can eat a turkey sandwich before a blood test and still have a glucose level that's not far over 100. But in the hospital, where I was not fasting, the glucose was coming back at 229, then 185, then 175. (Four days later it was 109 in a fasting state.) Given that bendamustine is an alkalyting agent like cyclophosphamide, those of you with blood sugar issues may want to keep an eye on things if you opt for BR.

I have found a few good resources on BR. There aren't many out there for a therapy that is becoming increasingly common. The best I have found on dosage and side effects is this document from the Veteran's Administration. The ever-helpful BC Cancer Agency also has a good PDF on bendamustine. The best paper on BR is Bendamustine Combined With Rituximab in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group. The abstract can be found here. If you want more than the abstract, send me a note at clldiary at yahoo dot com. I'm not always swift about replies but I promise to get back to you.

I am looking forward to my next treatment, which will be in Dr. Droll's office, with full-strength bendamustine. I'll report on what happens then, and whether I experience any delayed reactions to the treatment I have already had. Some patients have reported nausea, fevers, fatigue, rashes, constipation, diarrhea, and severe neutropenia. Some of this is a matter of luck (or lack of it) and I think age may also have something to do with how easily the medicine goes down. It's easier to handle heavy-duty chemo at 55 than at 75. Whatever your age, of course, the important thing is that it works. So far, so good.

It's chemo time

Treatment starts Tuesday. I have decided to go with bendamustine and rituximab (aka Treanda and Rituxan), the first round of which will be given in the hospital so I can be monitored for tumor lysis.

As readers of this blog know, I have been looking for a kinase inhibitor trial for some time. A series of events out of my control has kept me out of trials, and my clinical condition now demands something bigger and stronger.

I was invited into the CAL-101 plus ofatumumab trial at UCLA last August, only to be told that there was a mistake by the company that organizes the trials and that the slot didn't actually exist. Had this worked out, it would have been ideal, since I was still at Stage 2 with ample hemoglobin and platelets. It would probably have been a seamless transition from the lenalidomide (Revlimid) I was on, and it probably would have forestalled the situation I now find myself in. At last count, hemoglobin was 7.9, platelets were 96, and the lymph nodes are bigger than ever. My spleen is 6 cm below the costal margin and the liver is, in the words of my oncologist, Dr. Droll, "pronounced."

In March, I was invited into the ABT-199 trial at the University of Arizona Cancer Center. I went there for the testing that is required before entering the trial, only to find out that there was now a problem between the drug company, Abbott, and UA. Since then I have been able to piece together some of the story; it appears that a failure to do something right at UA lead to the suspension of recruitment there. Which left me with nothing other than the promise that I would have first crack when a slot opened in the AVL-292 trial, in which UA was also participating.

The slot for AVL-292 finally opened, and I was faced with a difficult fact: Hemoglobin of 9.0 is required for admission, and while mine had been a steady 9.2 for months, it dropped to 8.5 and now 7.9. So I wasn't going to get in the trial regardless.

The cart before the horse

This all dragged on much longer than anticipated, and as it did my hemoglobin began to head south. It became apparent to me that between my failing marrow and disease bulk, using a kinase inhibitor would be like trying to stop a house from burning down with a garden hose. Even if it addressed the nodes to some extent, it was almost assuredly not going to address the marrow, or do so with much depth and rapidity, and that is probably the worst problem I have at the moment.

I went in for a bone marrow biopsy on Thursday; I haven't heard the official results, but the person who did the BMB -- and all she does is BMBs, day in and day out -- said my marrow was "packed." I'm not surprised.

(For BMB fans, of which there are none, it is worth noting that they put me under for the procedure with propofol, as well as using lidocaine on my hip. This is the way to go as far as I'm concerned. I woke up a few minutes early and felt her digging the needle around in my hip bone; it was much more pleasant being knocked out.)

Ultimately, it makes a lot more sense to deliver as big a blow as I can to the disease now, and then follow up with a trial, probably a kinase inhibitor, as maintenance afterward. I might also consider using lenalidomide as maintenance; perhaps at a low dose I could tolerate it, and with less disease burden it might not be as overreactive in terms of tumor flare as it proved to be last November.

The choice

Basically, there are two choices for Big Chemo these days: FCR or BR. In my case, given the low hemoglobin and the fact that I had autoimmune hemolytic anemia from 2007 to 2010, FCR is just too risky. While the CR can moderate fludarabine's ability to trigger AIHA, it is still a risk, and one that someone with a hemoglobin of 7.9 should not take.

Bendamustine is newish, at least in practice in the U.S., and is supposed to be less myelosuppressive than FCR. Reading anecdotal case histories, one finds that most patients get through it with good results. There are exceptions, usually when neutrophils crash, triggering bad reactions, which is why using Neulasta during treatment makes some sense.

The most reputable paper on BR comes from the German CLL Study Group, which examined the treatment in a tough group of relapsed and refractory patients. The abstract is available here. For those who don't know, bendamustine was developed in East Germany. After reunification, it attracted the interest of researchers and drug companies. An alkalyting agent like cyclophosphamide, it also seems to have properties similar to purine analogues like fludarabine.

The full paper from the German group is worth reading. Bendamustine can work on those who are fludarabine-refractory, with 45.5% responding. It can also work on those who have had  rituximab, and I have had plenty in years past. Of seven patients who had previously received rituximab, five responded with a partial remission.

A disturbing fact involves Richter's Transformation. Four of 78 patients were diagnosed with Richter's Transformation after the end of treatment. The authors imply this was unrelated to treatment, but I'm not so sure. Richter's can be set up by profound immunosuppression resulting from treatment; just because it doesn't show up until later doesn't mean treatment had nothing to do with it.

The bottom line is that all therapy comes with risks; kinase inhibitors are not risk-free, as Chaya Venkat makes clear in a recent report at CLL Topics Updates.

What I can expect

Based on the German data and my clinical situation, I am hoping for a partial remission that significantly reduces the nodes and clears out the marrow to a great extent. I am not anticipating a CR, despite the optimistic words of Dr. Daruka Mahadevan at UA, who said BR would "clean me out."

This is why maintenance should be initiated soon after I complete BR in December. I need to keep the disease in check through some means; if there has been a lesson for me in my experience since November, it is "don't let up."

I will report on BR in some detail as I experience it; little has been written, even anecdotally, about patient experiences with the drug, and it is here to stay as a major player in CLL.

I'll be doing the first round in the hospital so I can be monitored 24/7 for tumor lysis. In someone with my disease bulk, so many CLL cells could die so quickly that my kidneys might be at risk. Both Dr. Mahadevan and Dr. Droll thought this was a good idea, and I can't argue. As much as I don't like the hospital, I like my kidneys. I also expect that Dr. Droll will go with a lower-than-usual dose of bendamustine in the beginning, another way to guard against potential problems.

And so the next chapter begins in my CLL Diary. I am looking forward to the treatment, which I hope will restore some of the quality of life that I have lost. I had seven years of relatively easy CLL; when things head south, one is reminded of how difficult (and, yes, how potentially deadly) this disease can be.

Thank you, Mr. Roberts

Word is out now that Chief Justice John Roberts switched his vote before Thursday's U.S. Supreme Court ruling on the Affordable Care Act.

And for that, I say thank you, Mr. Chief Justice. I could, perhaps, owe him my life.

I have been counting the months until 2014, when I should be able to purchase decent insurance through one of  the newly-established exchanges among states. The new law requires that they take me despite my preexisting condition -- chronic lymphocytic leukemia -- and that premiums be capped to that I can actually afford, like most middle-income people, to pay. If coverage is anything like it is in the current and temporary PCP -- the Pre-existing Condition Program that the ACA set up for adults who have been without insurance for six months -- it should allow me a much wider network, including out-of-state expert centers. And, unlike my existing insurance, it would probably provide for a stem cell transplant, should that day ever come.

This will allow me to get away from Merciless Healthcare Group, which was set up in Arizona as a state-backed plan for small businesses. Over the years what was once a limited HMO that took care of its members has become a penny-pinching HMO with ever-higher deductibles and co-insurance and an ever-shrinking network.

For example, the emergency room where I was diagnosed with CLL in 2003 is about a half-mile from my home. It is no longer contracted with my insurer, which no longer has a relationship with Northern Arizona Healthcare, the largest provider in the region. Today, to go to a contracted hospital I have to drive an hour and a half to Prescott, and that goes for getting CT scans or outpatient infusions as well. If you live in my county, you can't even buy into my insurance any more. I am what they called "grandfathered" in. (And, of course, no other insurer will touch me because of my CLL, at least until the ACA takes full effect in 2014.)

I suppose I should consider myself lucky to have insurance at all. Reading online forums, I have seen more than one CLLer describe attempts to deal with the disease without insurance. Chlorambucil may be affordable but it is hardly the standard of care these days. Neither is drinking a lot of green tea.

The whole question of the Affordable Care Act can be an emotional one for both sides. I plead guilty here. For me it may make a huge difference in quality of care, which could mean life and death. On principle, I also think a country that constantly touts itself as the greatest in the world should be able to provide real access to health care for everyone. American "exceptionalism" should not include an exceptional inability to create a workable medical system.

There was an anti-ACA sign held by one of the protesters outside the Supreme Court building while everyone waited for Thursday's decision. It read something to the effect of: "Obamacare: Thank you for paying for my poor life decisions."

CLL is not a product of poor life decisions, and neither are most cancers and chronic diseases. Sometimes shit happens. Let these people walk a mile in the shoes of the uninsured, or underinsured. Let them learn what financial and emotional strain truly are. Now that the election approaches, some Republicans talk of "repeal and replace," but in all the years they held power, at least post-Nixon, they never made an effort to address such matters as preexisting conditions. Given their continued lurch toward the hardline right, one expects they never will.

Please join me in voting Democratic this Fall, from the state level to the federal, to insure that the law is implemented as it should be. The ACA may be flawed in some ways, and it may need tweaking as it goes along, but is is a giant step for our country, and for many of our fellow CLLers, as well as other cancer patients.

Black thumbs, passing arms, and high fevers

Time for an update, as the saga drags on.

I have a new theory, which I'll call Dave's Black Thumb. It goes like this: If there is a doctor in Arizona that I like, they will eventually leave their practice and probably the state.

The first to go, in 2006, was Dr. Susan Partyka, known as "Dr. Chopin" in the blog. In January of this year it was Dr. Lesley Meng ("Dr. Belle.")

Which brings us to the present. Earlier this year, when Dr. Meng left, I found a new oncologist, but I also found another doctor to consult with who was conducting some interesting clinical trials of kinase inhibitors. This was Dr. Daruka Mahadevan at the University of Arizona Cancer Center in Tucson. (I paid out of pocket for to see him because my insurer, Merciless Healthcare Group, doesn't cover either of the state's preeminent cancer centers, the other being Mayo Clinic in Scottsdale.) Dr. Mahadevan was UA's CLL guy, and we hit it off immediately. He's smart, an honest arbiter of treatments, showed a willingness to fight for his patients, and was worth the $500. And now he, too, has flown the coop and departed the state for points unknown.

This means the reset button has been pressed, and now I need to see a new doctor in Tucson, who will be the new investigator for the one remaining trial (AVL-292) they expect to open "in a few more weeks." If I had a quarter for every time I have been told "a few more weeks" I really could buy a cup of coffee. (My last post went into problems with the trial that would have been the first choice, ABT-199.)   

I can't wait forever

Keep in mind that my disease has become much worse since last November and that I needed treatment in January, really. My hemoglobin has plateaued at about 9.2, which is just enough to get me around but not enough to do any meaningful physical activity. I think twice before walking up the stairs, for example. I tire easily and need to sleep more than usual.

My new local onc, who I think I'm going to call "Dr. Droll" because he has a dry sense of humor, has kept me going during this trial search with huge doses of pulsed steroids, which is a stop-gap of limited usefulness, not any kind of solution. This involves taking 40 mg of dexamethasone for four days every ten days, ostensibly. (I do it about every three weeks, when I feel baseballs forming under my arms again.) This regimen is used on myeloma patients. When I saw him recently and mentioned how much I hated the steroid regimen, his comment was "They don't clamor for it." 

The platelets dropped to 85 at one point but thanks to the steroids have been hanging around 120. The lymph nodes have gotten worse than ever (though surprisingly my spleen is almost petite). Left unchecked for awhile, the nodes clump together in masses under my arms and in my abdomen. The steroids knock them back some, then they bounce back after a few weeks. It's clear that my marrow is impacted and that the nodes need attention.

Dr. Mahadevan's suggestion for a conventional treatment was bendamustine-rituximab. Dr. Droll has the same point of view. Mahadevan said he "wouldn't give me fludarabine with a 10-foot-pole" because of my history of AIHA. I am not overenthused about bendamustine, but I do see the logic and it is less myelosuppressive than fludarabine. Either can lead to such lovely conditions as Richter's Transformation, and I have a lot of deep abdominal nodes.

It is exactly because the kinase inhibitors can do an excellent job of shrinking the nodes with much less toxicity that I have held on this long to search for a trial. But how long is it safe to continue waiting to get into one while taking enough steroids to revive the dead?

Which brings us to the Hail Mary pass I have thrown, which may result in some good news, and which may not, and I won't know until mid-July. I'm going somewhere a little further afield than Tucson, and I'll see what happens there.

But the window on this is closing; no trial soon = bendamustine-rituximab.

104 degrees

And I don't mean the weather. I have just finished a week, most of it spent in bed, with fevers that ranged from 99 to 104. Besides fever, the main symptom was exhaustion. My lymph nodes did not swell up beyond their already swollen point, which is usually what happens when I have a cold or flu. In a CLLer with limited immunity a fever of 104 is not a good sign. Marilyn wrapped me in an electric blanket and stuffed me under the comforter and we agreed that if it was not down within an hour, it was off to the ER. But it dropped, and I stayed home.

The good news is I got over It, whatever It was. The fever began while I was continuing on prophylactic meds for the steroids, although I was off the steroids, but the Bactrim, Augmentin, Fluconazole, and Acyclovir did not prevent It nor cure It. My own immune system overcame It, which is a very good sign.

And that's where things stand. I'll update you in a month.

Hurry up and wait

Those of us with chronic lymphocytic leukemia are familiar with the concept of "watch and wait," which means being a patient patient while your disease take its course. This can involve a certain degree of dis-ease (pun intended) as you and your doctor lurk about, waiting for just the right moment to begin treatment, should that become necessary. 

Of late I feel like I've been experiencing something called "hurry up and wait," which is what you do when your disease definitely needs treatment but you are waiting for the best treatment option to make itself available, which is supposed to happen Any Day Now.

"Watch and wait" drives Type A personalities a little bit crazy, which isn't really a problem for me. "Hurry up and wait," on the other hand, can be a bit of a challenge.

In my case, since the end of the Revlimid era last November, the CLL has taken a turn for the worse, compounded by departing doctors, insurance runarounds, and potential clinical trials that have proven to be trials in more ways than one. I've written about some of this, and am here to provide a little update now.

The good news is that Any Day Now there should be an opening in a kinase inhibitor trial with my name on it. I've been waiting on two such choices for a while. 

The first, which I'll call Trial One, almost came to fruition six weeks ago. In fact, I was all dressed up for extensive testing for a trial slot, only to arrive and find I had no place to go. Seems an "adverse event" in the trial of said inhibitor had just raised a big red flag at corporate headquarters and further patient accrual was being put off. All this happened in real time as I sat in my hotel, or in the Vietnamese restaurant adjacent to my hotel. Eventually I was sent home with the knowledge that while Trial One was probably out for the forseeable future, there was a Trial Two that would have an opening in another month, give or take.

And, so, here I wait at home, far from pho, disappointed but cautiously optimistic that I might make it into the second trial, in which no adverse events have been reported to date, at least that I know of.

You could argue that I am lucky the adverse event in Trial One didn't happen to me. It was an unexpected case of severe tumor lysis, apparently, which means massive, immediate die-off of leukemia cells that, uncontrolled, can damage the kidneys. Trials are called trials for a reason, and as much as we like to think of ourselves as intelligent, forward-thinking patients, we are also in fact risk-taking lab rats when we sign on the dotted line. So maybe I dodged a bullet by not making it into Trial One, which would not have been so disappointing had the principal investigator not been so genuinely enthusiastic about its potential to help me.

Now, I could go into names of drugs and names of doctors here, but what I have heard is second-hand, and I'm not in the business of reporting such things as absolute fact. This is a blog, not journalism, and there is a huge difference between the two that I still hold somewhat sacred, having worked in the news business back when double-checking the facts counted for something.

To keep my CLL at bay while waiting for trials, I have been taking huge pulsed doses of steroids every few weeks. My new local hem/onc calls it the "myeloma dose" -- 40 mg of dexamethasone daily for four days. The advantage is that it does reduce the nodes temporarily, and it has bettered my platelets a bit (they're now at 101) while perhaps also keeping my hemoglobin steady in the low 9s, which isn't so awful once you get used to it. Plus the steroids leave your system in under six days, and the prophylactic meds (antibiotics, antivirals, antifungals) also leave quickly, meaning that you can be ready to qualify for a clinical trial without a long delay.

Since 2007, I've had a fair amount of experience with steroids, about which I plan to write at some point soon. I think they're a good but problematic stop-gap, and nothing more. Steroids are a potentially useful component in any "hurry up and wait" strategy, but they're no way to live.

The late Dr. Terry Hamblin once pointed out that in end-stage cases he would prescribe steroids once a month just to keep the patient going, and I can see how, when all else fails, it beats the alternative. 

Fortunately, we now have more alternatives, such as the kinase inhibitors, as well as Revlimid for those who can tolerate it, not to mention the supercharged T cells being studied at such places as the University of Pennsylvania.

Which brings us to the real game to win here. I call it "slow down and wait." By that I mean, allow science to outpace your CLL by just enough that it can save your life. I feel like I'm cutting it close on this one, but there really is no other choice, except to go marching off to the Relapsed-and-Refractory Factory and await the end.

Call me irresponsible, accuse me of "dithering" in the face of my own unplanned obsolescence, but I am not comfortable with following a conventional wisdom that can change from one day, or week, or month, to the next. In CLL, action can mean progress, but it can also mean the illusion of progress. Doing something just to do something may not always be the most rational course. So I often find myself taking my chances with inaction.

"Slow down and wait" involves a certain amount of powerlessness, of accepting things you probably cannot change, among them the possibility that Fate might throw something at you, for good or ill. By making wise (or just plain lucky) treatment choices you might be able to control the disease long enough to buy more time, but there are no guarantees, since the disease can always take a turn for the worse at a whim. As to the pace of scientific progress -- and the availability of its fruits in your locale -- that is all luck, pure and simple. 

So far, I've been fortunate that science has done more since my diagnosis in 2003 than I, or perhaps anyone else, might have expected. My disease behaved decently until last fall, and now has settled into a new plateau, worse than it was but not getting worse, at least yet.

And Any Day Now, well, I hope to be trying a new treatment that might just control this thing. So I'm hurrying up and waiting in order to slow down and wait some more. Welcome to CLL.

Revlimid, in retrospect

Now that my year-and-a-half experiment with Revlimid -- aka lenalidomide -- is likely done for good, I think it's appropriate to sum up what I've learned.

Blogs tend to blurt out information that gets disconnected after awhile; my training as a feature writer tells me to sum up and provide context. For those chronic lymphocytic leukemia patients considering Revlimid, I hope my anecdotal experience might be of some use, which is why I am writing this.

I say "anecdotal" with all the usual warnings, as in YMMV -- Your Mileage May Vary -- and with this drug, it probably will. 

Pills are small and easy to take, but this one is not, on so many levels. For a little capsule that's supposed to be an "immunomodulator," it can easily provide more grinding fits and challenges than regular chemo. In CLL, lenalidomide comes with a wide degree of patient tolerance issues. One of them ultimately derailed the drug for me, but until it did, this stuff was almost golden.

Today, it is being eclipsed by the buzz about kinase inhibitors with license-plate names: CAL-101, ABT-199, AVL-292, PCI-32765, and so on. These drugs are in trials with promising results; while they may end up being a first choice over lenalidomide for many patients, in some cases they may not. Revlimid is here to stay for CLL, and it is a useful option to have. I used it from March 2010 until November 2011, with three months off starting in March 2011.

Revlimid modulates the immune system. Somehow. And in people with weakened immunity, such as CLL, this can do a couple of great things. One, it can cut down on infections, sinus and otherwise. In fact, it has been suggested that low doses of lenalidomide can be given to older people -- not necessarily CLLers, just older people who tend to get sicker easier -- as a means of keeping the immune system more functional. I have been fortunate in my CLL career not to have been especially infection-prone, despite my immunoglobulins being in the tank for nine years. While on Revlimid I was infection free -- not even a sinus minus clogging up my yap.

Revlimid normalized my blood counts, and it has done this for a lot of people. My absolute lymphocyte count wasn't too high to start with, as most of my disease is located in my 11q-deleted lymph nodes. But at one point my CBC became picture-perfect, frame-able even. You couldn't tell by the numbers that anything was wrong.

And this is a really big deal -- while using Revlimid, my very nasty, recurring case of autoimmune hemolytic anemia resolved. From the moment that the AIHA was diagnosed in March 2007, until Revlimid put a stop to it, I was bedeviled by serious hemolysis and treatments that began to fail, one after another, until I was left getting pretty heavy chemo (Rituxan, dexamethasone, and cyclophosphamide) as frequently as every three months. And there was some question about how long that could continue before a splenectomy became a necessity.

Dr. Asher Chanan-Khan, probably the country's leading lenalidomide-CLL researcher, told me in an e-mail before I started the drug that he had seen two actively hemolyzing patients -- hemolysis means your macrophages are eating your own red blood cells, which they will continue to do until you have none left and die --  whose hemolysis resolved while on Revlimid.

My own experience has led me to prosthelytize on these pages more than once, and so let me shout it out again for all my AIHA fellow-sufferers to hear: Please, please, consider Revlimid, especially if you are finding that the usual treatments (steroids, rituximab) are failing. If it does for you what it did for me, you'll have enough red blood cells to do some serious dancing in the streets. After a year of Revlimid, my hemoglobin was back up to 15.1 -- the exact number it was at on the day of my CLL diagnosis in 2003. I turned Coombs negative and remain so at this moment.

Revlimid also reduced my lymph nodes to a noticeable degree. I would say -- and I am guessing, since some nodes are more palpable than others -- by up to about half. In a nodey guy like me, that is great news. It took a long time. But it was slow and steady. And in CLL, slow and steady is often all you need to win the race, or at least to stay where you need to be when in competition with the growth of the disease.

Now, here's a real Revlimd success story. I have a friend with 11q-deleted CLL who went into a Revlimid clinical trial as frontline treatment. His lymphocyte count had reached a half-million (that's not a typo). In the trial, patients are upped from 5 mg daily to 25 mg daily over time, if they can tolerate it. And my lucky friend proved able to tolerate it, and to get the benefit from the maximum dosage. 

By the end of his two-year stint, his counts had normalized, what nodes were left were barely palpable, his hemoglobin was high, and a bone marrow biopsy showed improvement. Platelets were a bit low, but you can't have everything, and he's been told they should recover. He had found himself an excellent way to start out controlling his CLL without burning any bridges. He has had treatment, but not chemotherapy, which sets up disease resistance. From all indications, he can go on to do any other treatment out there, or take advantage of a new treatment that comes along, and he can expect it to work as well on him as if he had never been treated. (And, of course, he can always do more Revlimid at relapse.)

That is great news in the Second Chance department, which is so important in CLL,  and which cannot be understated. Preserving a second chance is what I was trying to do with single-agent Rituxan back in the days before Revlimid. That turned out not to work. Once you've done single-agent Rituxan, you have diminished your response to future treatments. It's not a free ride. But since Revlimid is an immunomodulator and works on totally different principles from chemotherapy, it does not appear to set up disease resistance. (Not that it won't make changes in the immune system, and only time will tell if there's something important about it that researchers and patients have been missing so far.)  But if I were starting out and needing treatment, I would seriously consider Revlimid for the Second Chance reason, as well as for its potential to do the job in the blood, nodes, and marrow that needs to be done.

And if I had been through the chemo mill, and was pretty much out of Second, Third, and Fourth chances, I would also look into Revlimid. There are some CLLers out there who have been kept alive for years now with daily doses of Revlimid. Fate has allowed them to tolerate it, and it works as well on the nasty 17p-deleted CLL clones that are left after the Chemo Wars as on the "nice" ones you tend to find more of at the start. For these people, Revlimid truly is golden.  

Dosages are tricky. Not everyone can tolerate 25 mg. Celgene, the drug's maker, has recommended that as a routine matter, CLLers not be given more than 10 mg daily. Some patients are coasting along at 5 mg, in maintenance. Some can tolerate 10, some higher. Some can't tolerate it at all.

In my case, doses as low as 5 mg have caused problems. I'll get into that in a minute. Suffice it to say that the higher the dose you can take, the more the drug will probably be able to do for you. Finding that right dose, and watching out for symptoms that could indicate drug intolerance, requires a great deal of patience. It helps to have a doctor who has used the drug in CLLers, or at least in those for whom it was originally intended, patients with MDS. You need to be aware of your body and on top of symptoms if you are going to experiment with it, and let's face it -- in CLL, Revlimid is still experimental.

Revlimid can also make you feel kind of out of it. Before I get into more serious tolerance issues, one thing my friend and I both noticed, and that some others have noticed, too, is that lenalidomide can bring a certain dullness to your life. I wouldn't say fatigue, necessarily. But this drug is the enemy of multi-tasking. It can lead to a lack of focus or sharpness. You can operate heavy machinery, you can go to work, you can do all the things you normally do, but somehow you do these things slower, or somewhat more detached, or in a somewhat foggy world involving less concentration. This is not a good-time, party drug. When Marilyn and I flew back East for my step-mom's big 70th birthday bash, I stopped taking Revlimid a few days before. I knew that if I were off of it, I'd be enjoying the party and making conversation. If I were on it, I'd be sitting in a corner trying to remember who so-and-so was from a distance. Suffice it to say that lenalidomide is no help with libido, either. While not everyone reports these sorts of symptoms, It's ongoing use could lead to a somewhat lower quality of life in some respects. That's not enough to make it not a choice, but it's potentially part of the experience (and for some it does get better over time.)

Revlimid can lead to serious clotting issues. This is one of those things that Celgene is very up-front about, and that the nurses who dispense the drug are always reminding you of.

By now, if you've read CLL Diary, you know that clotting was my problem, and that this shifted the risk-reward scale in favor of abandoning lenalidomide. To recap, I have a family history of clotting troubles. My mother died of a pulmonary embolism at 57,  just two years older than I am now. Her older son -- my older half-brother -- suffered several strokes, one of which took his life this past July at the age of 66. I saw him become bedridden and incontinent, barely able to move one hand, hardly able to swallow, eventually surviving through a stomach plug. I saw him decline, both physically and mentally. One night, a few weeks before he died, in a moment of frightening clarity, he shouted something from the hospital bed that had been set up in his living room: "What a miserable existence!"

It is possible to live with CLL and have good quality of life. In the QOL department, there are many worse conditions to have, not all of them cancerous. Staring my brother's fate in the face, I was ever reminded that worse things could await me if I were not careful.

I had two transient ischemic attacks, aka mini-strokes, while on lenalidomide, and then a third incident that probably qualified as something of the same. The first incident came about four months in, while I was on 10 mg daily, and involved about ten minutes of aphasia, or language difficulty. It resolved completely, and I ignorantly chalked it up to "chemo brain" and put it out of my mind. 

The second attack came some some months later, after things had been going so well that my oncologist gave me the go-ahead to up the dose to 15 mg daily. We wanted to go in and get at those nodes. After a week or so, the same language difficulty appeared again, also for about ten minutes. This time I went to see the doc, and she put two and two together, and clotting issues took center stage.

Which is why, like my lucky friend, who underwent a supervised trial in which Coumadin was required prophylaxis, I would not advise anyone to go on Revlimid without also going on Coumadin, or warfarin. Even if you don't think you have a clotting problem, it is wise to guard against it. If it is good enough for Dr. Chanan-Khan's patients, it should be good enough for your doctor's, too. Like any prophylactic drug we CLLers take -- such as allopurinol, acyclovir, or Bactrim -- it is designed to guard against a problem occurring. And at a low dose, such as 2 mg daily, it should not present a problem for most people. It is insane not to do it, IMHO.

The third incident occurred in September of last year, and came and went over the course of a week. By that time, I was on higher doses of warfarin, which were not improving my clotting time much at all, and lower doses of Revlimid, such as 5 mg three times a week. I felt a transient numbness on the left side of my mouth, sort of the way you feel after you've been to the dentist and the Novocaine has started to wear off. Simultaneously, I also felt this numbness in my left hand. This resolved after about 15 minutes, but it came and went for short periods during the following week.

Finally, of course, there is the story of my lenalidomide gotterdammerung and the abscessed lymph node, catalogued a few posts back complete with messy photos. Despite a year-and-a-half of being on the drug (and sometimes off of it), resuming it at 5 mg just four days in a row caused such unholy tumor flare as to land me in the hospital.

Which leads me to a final point: Revlimid can do unanticipated things to the immune system. In my case, it appeared to goose it up over time. There was a three-month period, starting in March 2011, when I was off the drug. I was, in part, expecting to get a slot in a kinase inhibitor trial, which did not pan out, and I needed to be "drug free" for 28 days before starting the trial.

Just before resuming Revlimid after this hiatus, I came down with a case of hives. This was unusual, since my allergies don't usually take that form. It resolved with Benadryl (speaking of Zombie drugs) and I went on to restart Revlimid at a general course of 5 mg three days a week. Over the course of the last summer, I was constantly getting hives, several times a week. Move me to a spot with a new allergen, and it would start. Let me get a little sweaty in Arizona in the summer -- which is impossible not to do -- and the the hives would come again. It was all easily controlled; in fact I began taking Allegra every other day just to keep it away. But something in my immune reaction was more hair-trigger, way more prone to act quickly than it had been in the past.

My theory -- and, again, this is anecdotal guesswork -- is that Revlimid, which had rewritten my immune system in some good ways, also rewrote it in some more dangerous ones. A recent paper by Dr. Chanan-Khan and others discusses mechanism of action at some length, and basically points out that lenalidomide works best when there are lots of NK and T-cells present. (The latter, little marvels, also surveil against squamous cell skin cancer, another problem I've had, and something common to CLLers; Revlimid appears to have kept a lid on those, too.)

The paper, Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response, is worth reading if you're thinking of taking the lenalidomide leap. It appeared in the May 15, 2011 issue of Cancer, which is published by the American Cancer Society. Now, here is where I teach you to fish. Most journals that usually charge for articles will provide one free for the personal use of a patient if you just write and ask. In this case, contact canceredoff at cancer.org. 

Tumor flare, the paper explains, predicts response in Revlimid. There is a two-thirds chance that you will encounter it. From the very beginning, tumor flare was always a challenge for me. It came on big when I first started the drug, then remained at a lower but tolerable level during treatment as the ongoing battle with the nodes was engaged. What happened at the end with the abscess was one for the record books. Again, just a guess, but I wonder if the Revlimid had created in me a condition by which my immune system overreacted when the Revlimid itself was re-introduced at a 5 mg sustained dose, higher than I had been taking for some time.

Talk about ironic. In many ways, I responded very well to Revlimid, perhaps a little too well. It created too much fire to play with.

But it got me through a rough patch when I needed it, and it saved my ass in 2010 and much of 2011, getting me in a bumpy fashion to the great hope of 2012, kinase inhibitors.

So, thank you Celgene. And if you, fellow patient, are in the right position to tolerate it, Revlimid could be an important option for treatment. Just consider that it may not be easy, and do expect the unexpected.

(A final note: readers will recall that I began my Revlimid regimen in 2010 along with infusions of ofatumumab, aka Arzerra. The Arzerra was stopped after September's dose as the Revlimid appeared to be doing most of the work; I was on (and off) Revlimid for another eleven months after the Arzerra ended, so I do not think it clouds the story much. The one thing it may have done is mitigate the tumor flare I experienced at the beginning; perhaps it also served to keep the immune-goosing effects of the Revlimid somewhat in check.)