Some good news on the AIHA front

After a struggle with autoimmune hemolytic anemia (AIHA) that extends back to March, I have finally gotten some good news: I am less Coombs positive than I was before.

The Coombs, or Direct Antiglobulin Test, measures whether there are antibodies to red blood cells (Bad immune system! Bad!), which leads to their destruction by macrophages. When I relapsed with AIHA in July, the test showed positivity for anti-IgG of 2+ and anti-complement of 1+. As of now, after a month and a half of steroid and Rituxan therapy, the anti-IgG is down to 1+, and the anti-complement has reverted to negative.

What does this mean? Well, combined with ever-improving red counts, healthy haptoglobin levels, and reducing reticulocytes -- what those things signify is discussed in that link above -- it means that I may, just may, be winning the battle with AIHA. Conversion to Coombs negativity, according to Dr. Kanti Rai, portends a much longer remission from this nasty CLL complication, and that is what I am hoping to achieve.

Dr. O’Leary, my hem/onc, wants me to stay on maintenance methylprednisolone for the foreseeable future, and so today I start my 4 mg maintenance dose. This is equivalent to about 5 mg of prednisone, which is standard in these cases, and which some patients are on for up to a year before their AIHA resolves completely. At a three or six month interval, he’s not sure which, O’Leary wants to add more Rituxan -- which he pronounces “Rye-tuxin” for some reason -- to goose the response.

As with anything related to CLL, there are no guarantees. The first test will be seeing if 4 mg is enough to hold me; we’ll do some blood work in two weeks to check the progress. (Fortunately, I have tolerated the steroids well at much higher doses, so one pill a day should be smooth sailing; moving back to two, if need be, would not be burdensome. The main side effect I have had from steroids of late is pimples on my chest. Go figure.)

What this could also mean is that I might avoid harder chemo for awhile longer. That would be the next step if steroids were to fail. Certainly, after my AIHA relapse in July, it was weighing heavily on my mind. But I am glad I didn’t panic and jump when I didn’t need to. (Here I followed my own Three-Day Rule, which dragged on to something like thirty days in this case.) While it is essential to stay on top of autoimmune symptoms and CLL complications, it also makes sense to use the least invasive method to treat them if there are no compelling reasons to use a stronger approach. The fact that I am responsive to steroids -- the first time around I was almost assuredly taken off of them too soon, which accounted for the relapse -- argued that steroids were worth another try when relapse came.

The overall state of my CLL was also not, I concluded, compelling enough to warrant harsher treatment. My CLL, in fact, is under pretty good control right now. My marrow is doing well: platelets are healthy, and my ability to pump out gazillions of reticulocytes (baby red cells) is a good sign. Nodes are reduced significantly, or as O’Leary puts it, I have less of a “bull neck.” My spleen is only mildly swollen (just the tip can be felt below the rib cage.) The liver, which became somewhat enlarged after my low-dose Rituxan earlier this year, is, according to O’Leary, “right where it should be.” My lymphocyte count is about 48k, actually down a few thousand from the previous test.

So, for the moment, I have achieved a reprieve. Marilyn and I will be taking a little trip, with some extra methykprednisolone packed away, not to mention prescriptions for acyclovir (in case of sudden shingles) and augmentin (in case of sudden infection) in my wallet. Such is the CLL (working) vacation, but I am glad to have one.

AFTERWORD

As it turns out, this was the calm before the storm.-- November 19, 2007

My friend Kurt

One of the few good things about chronic lymphocytic leukemia is becoming friends with other patients, and one of the worst things about it is seeing friends die of it. Kurt Grayson was a friend of mine who died this week of complications stemming from his CLL.

Kurt and I led very different lives before our diagnoses. Kurt had a career in Hollywood as an actor in movies and television. He had money, too, and a big house in the San Diego foothills replete with luxury and sports cars. For a time he lived life in the fast lane, both literally and figuratively. Not long after his diagnosis, which was around eight years ago, he lost everything in one of those California wildfires we see on the news from time to time. He moved north to Sacramento to care for his elderly parents and he became active on the ACOR CLL list and other internet discussion groups.

It was there, through his posts, that I met him. Kurt was a bit of a character, which I liked, as I suppose it takes one to know one. We found that we had certain things in common, including a questioning attitude toward the conventional wisdom. We also shared senses of humor and to a great extent outlooks on life. Kurt was not traditionally religious and neither am I. Our politics were similar. When it came to internet discussions, we both favored free and open approaches.

This kept Kurt in conflict, sometimes, with the ACOR list managers. Yes, Kurt could go on too long, and yes he was passionate in his views. Before Dr. Terry Hamblin arrived on the list and lent his credibility to the treatment protocol of chlorambucil plus Rituxan, Kurt was there urging people to consider it. It had, in fact, worked for him, buying him a remission of three or four years before he became refractory to it.

Kurt once told me the story of his visit to UC San Diego shortly after diagnosis. Dr. Thomas Kipps looked him over and said he’d be dead within a year if he didn’t start big-gun chemotherapy ASAP. Kurt proved Dr. Kipps wrong.

But one cannot cheat the disease forever, and it was finding a second act to follow the first that proved impossible. Kurt relied heavily on the internet. He became friendly with any number of doctors and patients and he consulted them from time to time. As so many of us have learned, advice about what to do with CLL is often contradictory. Kurt was always casting about for suggestions and weighing the pros and cons. Unfortunately, as time went on, his health worsened. And Kurt, focused as he was on caring for his parents, had not developed an in-person relationship with a CLL expert doctor and never found the time to venture to a CLL center for a workup.

In February 2006, Kurt and I, along with Steve Madden, Denise England, and Jenny Lou Park -- three other people of whom I have grown increasingly fond -- founded CLL Forum. Kurt was a moderator there but he didn’t get to spend much time on the job. His symptoms became acute and unusual; fluid would build up in his lungs and had to be drained. His spleen and liver were enlarged, and tumors of some kind were found on the liver. The old chlorambucil plus Rituxan, which had worked so well for awhile, ceased to be effective. Infections and pneumonia were a further problem. Kurt was in and out of the hospital.

This year, Kurt settled on FCR as a next step in therapy. By then his spleen had become huge, 32 cm in length. The drugs had no effect. Kurt became confined to a wheelchair.

About two months ago Kurt was pondering what to do as he was growing progressively weaker. He visited a CLL doctor at Stanford who told him, flat out, that he was dying. This shook Kurt up, as it would any of us. The doctor had few answers and suggested that Kurt go to UC San Diego or MD Anderson. Kurt had also been in touch with Dr. Richard Furman of the Weill Cornell Medical College at New York Presbyterian Hospital, who posts to a CLL discussion group on Yahoo. Furman was evincing an interest in Kurt’s case.

This is the situation as I found it when I gave Kurt a call. We had a long conversation about his options and about life and death. It is odd how we patients can become comfortable talking about things that make our healthy counterparts squirm; it comes with the territory of being in this battle together and facing what we face.

Kurt knew that he had to do something and was thinking of traveling to New York to be treated under Furman’s guidance. I supported this idea because I felt Kurt had a doctor who seemed to be interested in him and whom Kurt liked. Not every doctor wants to take on a difficult case. Kurt had to throw in his lot with someone and take action soon, before it was too late. It was the path of hope, however narrow.

And so Kurt went. Unfortunately, he had reached the point where his body simply began to shut down. He developed sepsis, followed by respiratory complications that required intubation, and then liver failure.

I write all this because it is the story of Kurt as I knew him and I don’t think Kurt would mind. He was always willing to share his experiences, for at his core he had a genuine desire to help other people so that we can all find a way out of this CLL mess.

(Kurt’s story is a reminder of the gravity of progressing CLL as I approach, on September 3, the fourth anniversary of my diagnosis. That makes it the start of my fifth year with the disease (five being the official count; my theory based on 1996 blood work is that this may actually be the start of my 12th year). Time, and CLL, marches on. I am not doing as well today as I was four years ago. Four years from now I will not be doing very well at all without some major intervention. Such is the nature of the beast we face, those of us who are not blessed with an indolent version of “the good cancer.”)

CLL consumed much of Kurt’s attention in the years I knew him. The old days of fast living were long gone; the fire in San Diego was a metaphor for the change in his life, for he had lost all his movie and TV stills and other memorabilia when his house burned down. Kurt seldom talked about the past, although he did once recall with some satisfaction playing strip poker with Farrah Fawcett during a break in shooting an episode of Charlie’s Angels.

The change in his life did not alter Kurt’s generous ways, however. He insisted on treating me and Marilyn to dinner in absentia when we went to UC San Diego to see Dr. Januario Castro last May. I declined, saying I appreciated the thought, but that I’d rather he save it for when we finally got to Sacramento to see him. A month later, when we set out to see Dr. John Byrd at Ohio State, Kurt again offered to buy us dinner. This time I felt it would be rude to refuse. Kurt liked to buy dinners for people, he explained, even if he could not attend. He had recently spent lavishly on a night out for a group of oncologists and their guests. And so we accepted a monetary gift, which was large enough to buy us a couple of nice meals.

We toasted Kurt then and I toast him today: Here’s to a kind-hearted man who approached his disease with determination and good humor, who reached out to others, and who touched many lives in the process.

We will not dine together here, but if there is a There there, Kurt, save a seat for me.

What a little Byrdie tells us

Dr. John Byrd, the CLL expert from Ohio State University in Columbus, had some interesting things to say in a recent telephone interview with the Leukemia and Lymphoma Society.

Byrd is one of my favorite CLL researchers because I think he calls it as he sees it and has good instincts about when and how to treat the disease. I say this not only as a patient who listens to his telephone and workshop comments, but also as someone who drove from Arizona to Ohio to see him for a second opinion and who knows several people who are patients of his.

Byrd, like another favorite of mine, Dr. Terry Hamblin, is a treatment conservative. Neither man seems to get caught up in the enthusiasm that prevails in places, namely MD Anderson, where some patients are led to believe that chemotherapy will cure their disease. (I am all for hope, but hope truly grounded in reality; speculative hope is an unkind cut to patients desperately seeking a way out of this box.)

Both Byrd and Hamblin are tethered to Earth by the logic of science, and in the reality of what CLL is, which means knowing how much progress we’ve made, but also knowing how much we don’t know. As Byrd told me, CLL is “a long journey.” It is for patients, and also for those who are working on ways to control and even cure it.

I recently caught up with Byrd’s June comments, which are in the form of a telephone education program called Current Progress in CLL Therapy and Clinical Trials. (There is now so much information available about chronic lymphocytic leukemia on the internet that one can start to suffer from chronic information overload. I am forever backed up in my reading.)

Byrd said some things that I found notable, and which show how thinking is changing and evolving. Reading the full transcript is well worth your while, but I have pulled out some of what I consider to be the highlights, including a surprise or two, here.

Bye-bye BMB (and CT)

The first thing that caught my eye is that the dreaded bone marrow biopsy, bane of many a patient, may be a thing of the past. Like many of you, I was given one, or subjected to one, or allowed to have the experience of coping with one, as a routine matter after diagnosis in 2003.

“We’re fortunate in that a variety of new molecular tests have come forward that really trump any advantage to the bone marrow biopsy showing useful information,” Byrd says.“ For most patients who come to see me initially with CLL, unless they have low blood counts or another reason that I would do the bone marrow biopsy, say I suspect an infection, generally we do not do a bone marrow biopsy at Ohio State. Most of the other CLL centers are moving towards this. Actually, the new NCI guidelines that will be coming forward likely within the next year or two are not going to advocate doing a bone marrow at diagnosis unless there’s another question to answer.”

I was also given a CT scan, and was threatened with having a CT scan monthly until I agreed to my first hem/onc’s demand that I undergo single-agent fludarabine. Hmm, monthly CT scans or finding a new doctor -- what to do, what to do . . . it was an easy choice. But I still know a lot of patients whose doctors insist on using the CT scan as a tool for routine tracking of the disease. Not Dr. Byrd:

“There may be an advantage in the future for CT scans in predicting how CLL is going to behave, but right now that’s really not established and it’s not a recommended test,” he said.

Prognostic tests and treatment time frames

How do you know how your CLL will behave? Byrd gave an overview of the prognostic tests he recommends, those things that trump the BMB, including FISH and IgVH mutational status. Much of this should be familiar to patients by now (see my sidebar at the right of this page, CLL Prognostics and Planning.)

What Byrd added of note, I thought, was an indication of the time frame that accompanies these test results. If your FISH test shows a 17p or 11q deletion, Byrd says “there is a 50% chance that at one year you’ll go on to require therapy. There is a very good chance that by three to five years virtually all the patients in that group will have to go on to therapy.”

As to IgVH mutational status, Byrd points out: “IgVH-unmutated CLL patients all eventually require therapy and the halfway point, where 50% of patients go on to therapy of 100, is about three years.”

So, as you can see, knowing those two pieces of information can give you an excellent idea of if and when you may need treatment. Unless you prefer the life of the ostrich, there is no excuse for not getting these tests done. (I should add here that Byrd finds value in the ZAP-70 test but cautions that it is “very unreliable” when done at commercial labs. My own experience, in which Quest Diagnostics had me as both positive and negative, bears this out.)

In summing up, Byrd says, “There are three things we do when we see somebody at Ohio State initially for their CLL to predict how their disease could behave in addition to an exam: clinical staging, looking at the red cells and the platelet counts; the interphase cytogenetics, or FISH; and the immunoglobulin gene mutational status. That helps pick patients whose disease is going to behave in a more aggressive manner versus a less aggressive manner.”

When to start treatment

Byrd gives an excellent rundown on the question of when to treat, including whether early intervention might be warranted in aggressive cases, as well as some of the complications that can accompany progressing disease. This alone is worth your reading the full transcript, but I will mention one highlight here.

As to the timing of treatment, he says (italics mine):

“Often patients are asymptomatic when they’re treated. They have big lymph nodes or lymph nodes that are increasing, but they’re not bothering the patient. Their white count is going up, but they don’t have any other symptoms of the disease. And therapy is recommended too early. I make that point because if you’re not having any symptoms from the CLL and you start treatment, treatment is likely going to make you symptomatic. We tend to be very conservative when we start treatment.”

A man after my own heart -- for the longer I deal with CLL, the more I think there is wisdom in the words of the American commander William Prescott, who said at the Battle of Bunker Hill (with apologies to my British friends): Don’t fire until you see the whites of their eyes.

Single-agent Rituxan v. fludarabine

I have been milking the single-agent Rituxan cow for nearly four years, to the point that it can barely moo anymore. One of the listeners asked Byrd about Rituxan maintenance, which I know a good deal about from experience. Here is his response:

“Unfortunately, there has not been a randomized study of maintenance rituximab in CLL after reduction of the CLL with chemotherapy. There is a study that I understand is going to be starting in Eastern Europe to look at this. The only data that exists for rituximab being given repetitively over a long period of time is a study that was done by Dr. Haynesworth (sic) in Tennessee. That study showed that giving four weekly doses of rituximab every six months for a period of two years resulted in a remission similar to that achieved by fludarabine.

“So my take on rituximab maintenance by itself for CLL is that it may add a little bit, but probably the biggest advantage for treating CLL is going to be giving rituximab in combination with other therapies. As a single agent it’s about as good as fludarabine as a single agent.”

Ahem. Did you notice that last comment? As a single agent, Rituxan is “about as good” as fludarabine?

Now there may be some who, in terms of the statistics about CRs and PRs and the like, will take issue with that statement. But I think Byrd is talking about the effect on balance, over time, on a person’s CLL as part of that long journey.

I wish I could bring this comment to my long-fired first hem/onc, Dr. Lippencot, who refused to hear the word “Rituxan” and who insisted on fludarabine, fludarabine, and more fludarabine. But if any of you are still out there, visiting local hem/oncs who have been hiding under a rock and who insist that you be treated with single-agent fludarabine, take notice: In the opinion of one of the world’s leading experts, it is no better than single-agent Rituxan.

Byrd says, as do all the experts and accurately so, that Rituxan works better in combination therapy than alone. Byrd also makes the point in his interview that your first treatment choice is your most important because it can give you the longest remission. Does this mean you should always go with the therapy that gives you the biggest bang?

That would be an interesting question to ask the doctor the next time he does an interview.

Personally, I think it depends on the type of CLL you have and how it is presenting itself. Your case may merit one of the combination therapies such as RF or RFC. But perhaps a gentler hand will suffice, and in those cases there is no reason not to consider using Rituxan alone, maybe with a pulse of steroids to reduce nodes: the question in CLL is not always what works best, but what, tailored to your situation, will work well enough while preserving options for the future. It was none other than Dr. Byrd who counseled me to save RFC for transplant preparation. CLL is a long journey, remember.

The '08 presidential contenders

Nothing brings the readers of this blog together like politics -- every time I write about it I transport some of you into a warm, fuzzy world of smiling dolphins, hopping bunnies, fluttering butterflies, and candy-scented breezes. NOT. But what the hey, it’s been on my mind lately, so I have decided to comment on how the 2008 race for president is shaping up.

Readers who may have missed the fact should know at the outset that I am a lifelong Democrat, a liberal with libertarian leanings, and that I think George W. Bush is the worst president since James Buchanan, who let the nation slide into Civil War. I saw a bumper sticker the other day that read “I never thought I’d miss Nixon” and realized how sad but true it is

I do not think the GOP has always been the rudderless pastiche of business interests, religious zealots, fearmongers, neo-conservative ideologues, and opportunists that it is today. Lincoln was perhaps our greatest president, Teddy Roosevelt was a credit to the nation, Ike was a decent man. Nixon, by comparison to Dubya, was at least smart and based his foreign policy on reality rather than fantasy. Reagan could talk in complete sentences, even if I thought many of his policies were misguided. Bush’s father was actually a halfway decent president, handling the end of the Cold War with aplomb and responding appropriately to Iraq’s invasion of Kuwait. I supported that Gulf War; I have never supported the disaster that Junior has unleashed, which is now the central focus of the 2008 campaign.

All this is apropos of the fact that when I look at the candidates, I try to look as an American as well as a Democrat, to figure out who actually might have the mettle to do the job in these difficult times. So far, I am surprising myself in how my thinking is evolving.

The Democrats

Before the Dems began their debates a few months ago, I was basically in the anybody-but-Hillary camp. I saw electoral disaster written all over her, and I was not fond of her support for the Iraq war resolution. She was about my fourth or fifth choice for a nominee, and I was looking more seriously at some others: Barack Obama, whose spidey sense about the war jibed with mine from the start and who is indeed a new, fresh face in a country tired of the same-old same-old; John Edwards, who seems to have learned from his Iraq mistake, who is addressing health care in big way, and who has the potential to run well in regions like the South where Democrats have had trouble; Bill Richardson, who brings a great resume to the job and who as governor of New Mexico might help my party make dents in the Mountain West, a traditionally Republican region that is making its way leftward in fits and starts.

Then I saw the debates, all three so far. And I realized that the one thing I want in a president is an adult, someone who does not need on-the-job training. We are still suffering through George W. Bush’s on-the-job training and look at the disasters it has wrought. Now, admittedly, most presidents are faster learners than Bush -- no, he's not smarter than a fifth-grader, to borrow from the title of the popular TV game show -- so I am willing to forgo a little experience if a candidate seems to have the right sense of judgment, depth, and wisdom.

Looking at the field, I see two good presidents: Hillary Clinton and Joe Biden. Clinton has distinguished herself mightily in the debates, scoring points for concise and sensible answers, for her bearing, and for her skill in taking advantage of her opponents’ mistakes. Her performance has erased any doubts I had that she could stand up there on a stage and best whomever the Republicans nominate, and I can also see her in a room being tough and smart and commanding when meeting with foreign leaders.

Joe Biden was a surprise to me; direct and to the point, experienced, with a plan for a political solution in Iraq. Alas, he has neither the money nor the following to get nominated.

Obama has been, on balance, a disappointment. He has “good bones” to use a real estate term, but like a house with great potential he needs work. The recent flap over “Would he meet with foreign leaders?” like the presidents of Iran, North Korea, and Cuba shows his inexperience. Hillary is right; a president keeps her cards close to her vest, lets underlings do the groundwork. Then Obama made things worse by announcing that he’d send troops into Pakistan, if need be, even without the permission of the government there. Now, we may have a secret plan to do just that, and if a president were to strike when the iron was hot to get Bin Laden there would be few complaints. But, again, presidents must hold their cards close; sometimes it is best not to telegraph such intentions, which risk destabilizing an important but shaky ally, just to prove you can be a tough guy. This is all rookie stuff, and it puts me off.

Edwards has great hair. Once again the media and the pundits are focusing on the inconsequential when there are real issues to be had. I have always sort of liked Edwards (though I voted for Howard Dean in 2004) and I have always sort of felt uncomfortable with him. Anyone running for president is ambitious, but I have always detected more ambition than depth in Edwards. Nonetheless, he is hitting the right points on many issues such as health care and the corporate influence in Washington and I have not ruled him out. He has the potential to run well across the board and we Democrats should never keep “electability” far from our minds.

Richardson has been the biggest disappointment. His debate performances have been lackluster and tongue-tied. His answer to health care is “more preventive medicine,” which is not exactly what I am looking for when it comes to access to insurance, insurance for those with pre-existing conditions such as CLL, and the like. He just doesn’t seem to have the bearing and quick thinking that would get him through a presidential campaign. (Now, vice president, that’s another story . . .)

There are the others: Chris Dodd, who is almost a caricature of a senator, Dennis Kucinich, who says many things that appeal to me viscerally but who looks like an elf and could never be nominated or elected; and crazy Grampa Mike Gravel, who reminds me of Dana Carvey’s Saturday Night Live character “the Grumpy Old Man.” But it’s great to have him there, on the end of the stage, keeping them honest and lobbing politically incorrect bon mots.

Finally, there’s Al Gore, my hands-down favorite and the man whom I truly believe was elected president in 2000. I wish he would run but he won’t. I have always sensed that Gore was in search of his soul -- and now, with his global warming crusade, he seems to have found it. His mission is important, and I hope he wins that Nobel Prize, and I still shed a tear for my country that a 5-4 vote of the US Supreme Court blocked a recount that would have probably led to a different, better path for us all.

The Republicans

Ah, what a great time to be a Democrat. The Republicans have a crop of flawed candidates and are about to sink the only one who might actually stand a chance next year.

I used to be afraid of Rudy Giuliani as a nominee. There was the thought that he’d run well in Democratic areas such as New Jersey and Pennsylvania. But the more I see and hear his rather shrill and grating personality, the more that comes out about the backstory to 9/11, the more we see of his family relationships, the more I think he will start to sink like a rock at some point in the general election. Bring him on, GOP. As one commentator said, he’s like Bush on steroids. People are tired of Bush, and they’re tired of people who think the only way to get elected is to use fear of terrorism as a mantra. The man has no national experience, and he’ll turn off large numbers of conservative Christians. Go Rudy! Go Rudy!

Mitt Romney is pretty good on his feet in a debate but he suffers from a couple of problems. One is that he’s said a lot of liberal things in the past that make him look all the more opportunistic now that he’d trying to appear conservative. The other is his bearing, which is, how shall I put it, rather John Kerry-esque. There’s an elitist sense about him and it won’t play all that well in the heartland. Unfortunately, his religion -- Mormonism -- makes some people uncomfortable. From a cynical political point of view, this is an advantage for the Democrats, but as a country I hope we have gotten beyond irrational prejudice in our deliberations. Like Obama's race, Clinton's sex, and Richardson's ethnicity, Romney's religion should make no difference to our vote.

Fred Thompson is the great unknown, at least to me. I don’t know how well he’ll come across, and whether he’ll be able to build a coalition beyond the GOP. I do get the sense that there’s nothing exceptional or extraordinary about him, and I don’t really see him capturing the national imagination. He is probably more of a placeholder than a force, and can probably not muster a groundswell of support or affection as Reagan did.

Which brings us to the last of the major contenders, John McCain, my home state senator. I kind of like McCain. I don’t agree with him on enough things to actually vote for him, but I appreciate his independence of mind, his sense of humor, and what I see as a genuine desire to do right, to be a good public servant. History often turns on “what-ifs” and I wonder how things might have been different today had McCain, not Bush, been nominated in 2000. John McCain could have been, and probably would be, a capable president.

Alas, we are where we are, and McCain suffers from his own dedication to the truth as he sees it. Americans complain that they don’t like to be pandered to, but when candidates takes unpopular positions they go unrewarded. McCain’s enthusiasm for the war is something I regard as misguided but it is at least genuine; his support for the failed immigration reform package sealed his fate with those in the party who see no room for dealing with the realpolitik of the situation. McCain, who was a prisoner of war, is also is the only Republican candidate willing to take a strong stand against the abuse of detainees (and how sad is that, here in the land of habeus corpus). This is to his credit, and McCain would still play pretty well in a general election. But his odds of making it that far are getting slimmer and slimmer.

The spouse in the White House

The GOP has a tough road next year regardless, but it lacks an inspirational figure who can unite the party, let alone the country. As much as Hillary might be hard to take for some people -- and I think for some, a strong woman of any stripe is off-putting -- she is likely to grow on people with time. Nobody doubts that she’s tough, or that she’s smart, and those are qualities we want in a president.

There is always talk of presidential spouses and how they help or hurt; Michelle Obama stands out in a positive way, as does Elizabeth Edwards. Bill Clinton stands out most of all; ever popular in the heartland of the country, he will be of immeasurable help in making Hillary a more accessible personality to those who may be a little unsure about her.

I vote on February 5, which is becoming known as Super-Duper Tueday, the day when something like 20 states vote. I figure by then the Democratic race will be down to Hillary v. Obama or Hillary v. Edwards. Much to my amazement, I am leaning toward Hillary. I have a feeling that come November 2008, a lot of other people will be surprising themselves, too.

The celebrity "solution"

Talk show host Tom Snyder has died of “CLL complications” and coach Bill Walsh may have done the same (some news reports saying he had CLL, others just "leukemia.") Not long ago the passing of journalist Ed Bradley brought the “good cancer” into the public eye, however briefly.

Whenever a celebrity of sorts comes down with chronic lymphocytic leukemia there are patients who get a little excited, hoping that we have at long last found the poster boy for our cancer (I say “boy” since most of the celebs with CLL seems to be men, at least that we know of.) Michael J. Fox has become associated with Parkinson’s Disease, Lance Armstrong with testicular cancer, and so on. There is a perception among some patients that having a "name" will gain our Rodney Dangerfield leukemia the respect it so richly deserves, after which bucketfulls of money will rain down from the sky, magically translating almost overnight into a cure.

Now, if Oprah or Bill Gates or Bono or Bill Clinton were to come down with CLL, we might actually see something like that, or at least the money part. But pending such an A-list victim, I think we have to be a little more realistic here. Having a celebrity speak for us could backfire, especially if the celebrity is old and male, which just confirms the perception that CLL is an old man’s disease that people die with and not because of.

Tom Snyder shunned the role of CLL spokesman. I remember when he announced two years ago on his website, Colortini, that he had CLL (see excerpt at end of this post). There was much excitement on the ACOR CLL list and he was bombarded with helpful tips, suggestions, and not-so-subtle proddings that he could do us all a lot of good if he decided to actively speak about his disease. Snyder said very little as time went on, other than to announce on his website before shutting it down that he had decided to “follow the protocols of Dr. Michael Keating” to treat his CLL. So I presume that he had RFC or the like.

That he managed to die of CLL complications within two years of diagnosis and treatment is unusual, and we should not jump to conclusions about his treatment choice or approach to the disease. But the fact is that a celebrity is no more capable of making the right choices about CLL than you or me; if anything, used to getting “the best” and feeling public pressure to do what is “expected,” they may not be quite as capable of thinking outside the box. (Add to this the fact that many celebrities are not too bright, and many really are as shallow as they appear. I have this on good authority from Marilyn, whose father is a retired Hollywood publicist.)

I believe it is thoughtfulness -- and thinking outside the box -- that we need if we are to get closer to a control and cure. Sure, it would be nice to have more money -- especially money that did not come with strings attached from drug companies -- but another area that needs attention is the culture of research. This is true of the cancer community in general.

Here is where I urge you to read Why We’re Losing the War on Cancer by Clifton Leaf, an article that appeared in Fortune a few years ago. (PDF here, if you prefer that to html.)

On the plus side, it is good to hear Leaf say, “The few dramatic increases in cure rates and patient longevity have come in a handful of less common malignancies -- including Hodgkin's, some leukemias . . ."

That's as far as he goes with anything that might be CLL-specific, but the way research is conducted affects us as well as everyone else, and that’s where, Leaf argues, some changes in the “cancer culture” may pay off.

Here's a taste of the article:

“So why aren't we winning this decades-old war on terror -- and what can we do now to turn it around?

“That was the question I asked dozens of researchers, physicians, and epidemiologists at leading cancer hospitals around the country; pharmacologists, biologists, and geneticists at drug companies and research centers; officials at the FDA, NCI, and NIH; fundraisers, activists, and patients. During three months of interviews in Houston, Boston, New York, San Francisco, Washington, D.C., and other cancer hubs, I met many of the smartest and most deeply committed people I've ever known. The great majority, it should be said, were optimistic about the progress we're making, believing that the grim statistics belie the wealth of knowledge we've gained -- knowledge, they say, that will someday lead to viable treatments for the 100-plus diseases we group as cancer. Most felt, despite their often profound misgivings about the way research is done, that we're on the right path.

“Yet virtually all these experts offered testimony that, when taken together, describes a dysfunctional "cancer culture" -- a groupthink that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs; that fosters isolated (and redundant) problem solving instead of cooperation; and rewards academic achievement and publication over all else.

“At each step along the way from basic science to patient bedside, investigators rely on models that are consistently lousy at predicting success -- to the point where hundreds of cancer drugs are thrust into the pipeline, and many are approved by the FDA, even though their proven "activity" has little to do with curing cancer."

In other words, we need to be thinking outside the box, making jumps and connections that might achieve genuine breakthroughs. Wars are won not only by slow and incremental attack; sometimes fortune favors the bold.

I wish we could send Dr. Keating and the other top dozen CLL experts in the world on a retreat and tell them, “Take your time, Money is no object. Forget your egos. Talk about the offbeat ideas you have been husbanding in the back of your mind, share your wish lists, sit around and drink too much Scotch and shoot the bull.”

And I would stick some creative thinkers from other disciplines in the room with them -- Steve Jobs-types, and our own Chaya Venkat -- to challenge their notions and light fires in their imaginations.

And then let’s set up a little private research center where the experts and the thinkers can come and work anonymously, creatively, crazily.

Would something come of it? We’ll never know until I win Powerball or Oprah starts noticing lumps in her neck.


EXCERPTS FROM TOM SNYDER'S BLOG

Below is an excerpt from Tom Snyder's blog discussing the discovery of his leukemia. I always liked Tom; he was pixilated, which the dictionary defines as "behaving as if mentally unbalanced; very eccentric. Whimsical; prankish. Slang Intoxicated; drunk." Here's to you, Tom; I hope they serve good martinis up there, and don't talk the Big Guy's ear off.

A cat scan turned up some interesting stuff. My spleen is enlarged, which the doctors say might be crowding my stomach in my abdomen, thereby causing some of the bloating I am experiencing. And judging by my white cell count and a variety of other factors including what was shown on the cat scan, I have been diagnosed with something called chronic lymphocytic leukemia. Jesus H. Christ! When I was a kid leukemia was a death sentence. Now, my doctors say its treatable! With pills or chemotherapy or a combination of both. Lemme pause here on this word treatable.

Four years ago they stuck a defibrillator/pacemaker in my chest because my heart disease was treatable! A year and a half ago a nearly torn tendon in my left leg was diagnosed as treatable. Then I came down with atrial fibrillation, but was told not to worry about that because it is treatable! I don't know how much more room I have in my aging carcass for this treatable shit! Anyway, my doctors assure me this is nothing to worry about, and I have to accept that, I guess. They say this kind of leukemia is not fatal, that people can live with it for thirty years. Notice, they don't say people will live thirty years. But they "can" live up to thirty years. Considering I will be sixty nine years old next month I ain't looking for thirty years, but fifteen more would be nice! I looked up chronic lymphocytic leukemia on the Internet and found a source that predicted people who are diagnosed early can live up to twelve years. Those who are not diagnosed early--and the website does not define "early"-- have a survival rate of about two years. I don't know if my diagnosis was early or late.

My doctors say this disease (which I'll refer to as CLL from now on) has a very slow rate of progression. I had more blood work done today to make certain this diagnosis is correct. The doctors will have the results of this in a week or so and then we will see what treatment they recommend. I am going to Northern California for about two weeks and I am not taking my leukemia with me. The doctors say that's okay with them.

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.

Checking my pulse

Inquiring minds want to know: Geez, Dave, it’s been a long time since you posted on your blog. I haven’t seen you around CLL Forum or ACOR. Are you dead?

This reminds me of the days when Marilyn and I managed our family’s summertime resort (and I use the term loosely) in the heart of New York’s Borscht Belt. It catered to an older clientele, many of whom had been coming as guests every year since the Hoover Administration. Breakfast was served at 8:30 each morning and one always had to keep an eye out for those who did not show up for it. People in their 80s do not skip breakfast, especially when it is one of three meals included in their rate. One day a guest approached the front desk and told me that her friend Alice was missing. This is how I discovered my first dead person, slumbering eternally in a red rocking chair in her room.

So I do appreciate that those of us who live with life-threatening things, like old age and leukemia, keep an eye out for one another. It is one of the sweet things about our community. I am here to say that I have been distracted, not dead.

First off, most people who are active in the CLL community are either retired or on disability, and Marilyn and I still run a full-time business. We are prisoners of eBay. Perhaps you’ve seen those TV commercials showing happy couples on their sunny decks next to their palatial homes, icy red cocktails positioned just-so next to their laptop computers, with a voice-over that goes something like this: “We made $5,000 last month running our part-time online home business. Next month we plan to make $20,000!” I am here to tell you that the only real thing in that picture is the drinking.

I have also been working on a very long post for this blog with the working title The roar of the engine, or chemo comes closer. As you can surmise, I am reaching some conclusions about dealing with my CLL. As I look at the post in draft form I realize that it sums up how my views have evolved when it comes to managing and treating the disease.

But I am not one to rush things into print. Sure, there are ideas I’d like to throw out now and then, especially posts on topics that are off the CLL reservation: How did we just spend $340 at Costco when we only went in to buy a new phone? Spider catchers: Low tech v. high tech (I may yet do that one). And for my Republican friends, George W. Bush: The truth revealed.

But, alas, I hold myself back, for I believe that to be a good writer you have to be a good editor. And so I will leave you for now with two quotes and a photo that has nothing to do with anything. Let’s call it the summer of my non sequitur:

Shakespeare, of course, said “Brevity is the soul of wit.”

Voltaire did him one better and said: “The secret of being a bore is to tell everything.”

And now for the picture: Below is my brother-in-law, holding my four-month-old human nephew on one side and my 19-year-old feline nephew on the other. Talk about the whole kitten kaboodle. Apparently cats and infants can be carried around in much the same way. I thought it was an amusing picture; it is a reminder that life goes on and that for everyone like Alice who leaves it, another beautiful soul enters into it. We are all one in that circle.