Thursday, September 03, 2009

My six years of CLL, and six things I’ve learned

September 3 is here, the sixth anniversary of my big doo-doo surprise. It was on this date in 2003 that I awoke from a dream in which the room was spinning. It turns out that the room really was spinning, which meant a visit to the ER, which was followed after a couple of hours by my diagnosis of chronic lymphocytic leukemia. I was told it was a “good cancer” and sent home.

The room, as it were, has not stopped spinning since.

I was going to title this post “Six years of this crap,” but I think it’s best to look back with a more even tem
perament at some of the big screaming bullet points that I have run across. These are things that may be the most help to those of you who are waking up into your own CLL bad dreams.

Since 2003 I have come some distance in my understanding of the disease and what it means to cope with it. Time is a teacher, and I’m sure it has a lot more to throw my way at least I hope it does, if you catch my drift. At six years in, I’m in my CLL middle age, both in terms of disease progression and knowledge. When it comes to the latter, I'm no longer wet behind the ears, yet wise enough to know that the learning curve goes on forever.

Here are some things I’ve learned, sometimes the hard way. They may represent a change or an evolution in thinking over some older posts in the blog. They are the truth as I see it today:

1. CLL is not the same disease for everyone. The “CLL is an indolent disease/good cancer” monster has to be staked through the heart every time it gets out of its coffin to suck your blood. It is the old, cobwebby way of thinking about CLL. Wipe those cobwebs from your eyes, unless you enjoy being mesmerized while your life drains away.

Some of us have relatively mild CLL, some of us don’t. Some of us respond really, really well to easy, breezy treatments, and others of us barely respond to nuclear chemo. This is because, for all practical purposes, we don’t have the same disease. A dog is a dog is a dog, but not all dogs are alike: Paris Hilton would look a lot more chewed up if she were carrying around a pit bull instead of a chihuahua.

Figuring out what kind of CLL you have does no
t involve reading tea leaves, poring over entrails, or consulting the shell of the prescient tortoise. It’s a matter of looking at the results of the tests available IgVH mutational status, ZAP-70, FISH, CD38 and at your clinical history (how fast your nodes are growing, how quickly your lymphocyte count is doubling, how far your hemoglobin and platelets are dropping). When I was diagnosed, the only readily-available test was CD38, so a lot has happened in six years. If you want to know what you’re dealing with, get your tests done.

2. See a a CLL expert (or two) at the very outset. Ol’ Doc Lippencot, highly regarded as she is around these parts for curin’ breast cancer and lice and possum infestations and such, didn’t know much about CLL. This is often the case with the local doctor, whose stock in trade is usually not going to be a disease that affects almost nobody.

And while patient networks and educational websites are excellent for moral support, learning about case histories, and keeping up with the latest research news, they are of limited medical expertise. This is because they are filled with seekers and guessers such as yourself, not to me
ntion the occasional insufferable blowhard. Some of these people are downright brilliant, some of them are extraordinarily helpful. But in the final analysis they are, like yours truly, amateurs what the dictionary defines as “lacking the skill of a professional.”

Which brings us to the professionals. Experts live and breathe CLL and
have seen hundreds of people just like you, with all the variants of your disease. They have a clue. This does not make them infallible. Having consulted a few, I can say that they don’t always agree. Just as painters see the world differently, so do those who practice the art of medicine. So see a couple of the big names — or even a few, the worse your case is just to get a consensus, or maybe that much more confused.

Our CLL experts are a great bunch many of them are approachable by e-mail but they’re not miracle workers and they’re not gods. Sometimes they run out of things they can do to save your life. Dr. Terry Hamblin told me in an e-mail once that, the way things stand today, doctors can only keep me alive for so long. I forgot how long “so” was — it appears to be at least six years — but the point was well taken, which leads me to:

3. The battle has a beginning and an end, and you need to be re
ady to fight. For those of us who don’t have indolent “goody-two-shoes” cancer, the day will come when we beat it or are beaten by it. The opening round came when that first mutant CLL clone got out of your own personal Pandora’s Box. The final round will come when it comes, and for many of us younger patients it will probably end with a transplant, win or lose (or there can even be a draw, of sorts).

Obviously, you need to be as prepared as possible. That is why patient education is important, getting the lay of the land is important, staying up with truly useful news is important, staggering your treatments intelligently is important, doing all the strategy and tactics stuff is important.

And that is also why learning to cope emotionally is important, and why this battle hinges at its heart on more than science and medicine. Healing is a big, mysterious thing. Books have been written. Bullshit has been blathered. But there is a lot about the mind-body connection that we don’t understand. Well-respected, level-headed doctors see “medical miracles” during their years of practice. I believe your chances of healing are better if you put your heart and soul into it, and the evidence seems to back me up.

Emotional preparedness can also help you cope with the inevitable surprises and slip-ups, the disruptions and disappointments (and occasional triumphs) that come with fighting cancer. It is a rough journey, a test of your faith and your stamina, something that demands that you get your inward act together.

You can walk out into the ring with all the technical skills, having read hundreds of papers and abstracts, having consulted every expert doctor within a ten thousand mile radius — but if you don’t learn to float like a butterfly and sting like a bee, if you can’t get in your groove, make knowledge and soul work together, you are fighting with one hand tied behind your back.

4. Be a pain in the ass. No, I don’t mean be a cry-baby or a whiner or a ninny (take that blood draw like an adult!). I mean learn to stand up for yourself in medical settings, learn to question things if you are uncomfortable, learn to say “No” and “Are you sure?” Do not be railroaded by doctors, office staff, or well-meaning family or friends. Be as diplomatic as the situation allows, but keep in mind the words of Teddy Roosevelt: “Speak softly and carry a big stick.”

This is where those emotional/intuitive clues come in handy. If someone says, “This is right,” but it doesn’t feel right, honor that thought. Float like a butterfly, and whack! with that stick. And the bigger the thing, the bigger the pain you must be. Do not stand on ceremony or save face; it will be at your own peril. The face you save could be
you own.

5. You cannot predict the future with certainty. So far, CLL has humbled the great minds of medicine, so get your humble on. Nobody can predict the future. Nobody can know an outcome for certain. Sure, a lot of cases follow the conventional wisdom;
things often, unfortunately, go by the book.

But there are exceptions. Let me tell you a story:

A patient has a sudden relapse, finds herself refractory to every therapy, has to live on transfusions. Like a Greek chorus, there is whispering offstage: “She should go into hospice.”

And now, two years later, like some mighty Greek goddess who has triumphed in an epic battle, she has survived a sudden transplant and is doing pretty well, thank you.

Bad things often happen in CLL, but good things can, too. This is not an article of
faith, it is a matter of medical fact. There really IS hope, tempered as it is by this thought:

6. In the end, it often comes down to luck. Dr. Allan Hamilton is a respected neurosurgeon, and the author of a book called The Scalpel and The Soul, and his number one piece of advice after decades of practice is this: “Never underestimate luck good or bad.”

The more I see of CLL, the more I believe t
his to be true.

Why do some people live and some die? My ever-practical younger brother puts it this way: “When your number’s up, your number’s up.”

It’s called Fate. This is why the best-prepared sometimes fail, why the least-prepared sometimes live. That’s no reason not to
care, no reason not to make the odds as much in your favor as you think you can make them.

But nobody gets off this planet alive. Dr. Hamilton has a blog, and he talks rather poignantly (tearjerker alert) about a couple who drive up a mountain to share a glass of wine in the twilight of life.

So enjoy wine and a sunset, whatever day it is for you. Life is not all about the battles we wage to stay here. It is about how we live it while we are blessed to be here.

That can be easy to forget when you’re in the trenches battling cancer. But with time and wisdom, we can learn to savor what life is about de
spite the challenge it has thrown at us. And life can become all the more sweet in the face of the dangers ahead.

Nobody said beating CLL was going to be easy, but n
obody who knows what they’re talking about says it can’t be done.

So here’s to six more years (come to think of it, I think the number “12" was in Dr. H’s e-mail somewhere).

With this post, I am stepping back from the blog for awhile. I have some fighting trim to get into. There are other things in life I must attend to. Over the years I have said a lot, but sometimes there is wisdom in being quiet and listening. I promise to post every few months, and I will let you know if I encounter any big health emergencies or breakthroughs. In the meantime, no news is good news. Take care, and stay as healthy as you can.

Sunday, August 16, 2009

The chemo monster mash: FCR vs. FCA

An interesting therapy comparison has come out in recent days, worth a mention to those who want to update their scorecards.

In this corner, weighing in at a zillion tons, breathing enough fire to melt Mt. Fuji, is our current champion, the Godzilla of CLL clemotherapy -- FCR (Fludarabine, Cyclophosphomide, and Rituximab, Genentech's long-standing anti-CD20 monoclonal antibody).

And in this corner, causing the earth to shake with the whip of its newly-minted tail, is the Mechagodzilla of CLL chemotherapy -- FCA (Fludarabine, Cyclophosphamide, and Arzerra — aka ofatumumbab, Genmab’s competing anti-CD20 monoclonal that is now very close to approval by the FDA).

We all know that the loser is going to be Tokyo. And the winner is . . .

Both, or neither, depending on how you look at it!

Genmab just announced the Phase II results of a tr
ial of 61 chemo-naive patients who were treated with FCA. Those who received the largest dose of ofatumumab (which also used to be known as HuMax-CD20) got a 50% complete response rate as measured by the 1996 National Cancer Institute CLL guidelines. (According to Genmab, the CR rate was 32% in patients who received 500 mg of ofatumumab and 50% in those who received 1000 mg. The overall response rate was 77% in the 500 mg group and a slightly lower -- go figure! -- 73% in the 1000 mg treatment group.) Obviously, the study is ongoing, so we don’t have any idea how long those “complete responses” will last.

Compare Genmab's results to those reported by the respected German CLL8 study group in 2008 in a trial of 817 patients randomized to receive either FCR or FC. The FCR group received a 52% CR rate using the 1996 NCI criteria. Assuming some basic equivalency between the studies, that’s a two percent difference, statistically insignificant.

on-free survival in the German study was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm. But the difference for overall survival was not significant (91% v 88% at 2 years).

(MD Anderson has been providing its own ongoing retrospective, non-randomized information that paints a rosier picture of FCR; it is worth noting Dr. Terry Hamblin's comments here.)

Which brings us again to the perennial question: What's the "best" choice for your first therapy, and how does that impact what you
do after relapse, when it's time for that second act that we often tend not to think about?

In my case, having pretty much used up Rituxan, it’s going to involve some Arzerra in the hope that it works better as a second-act agent, which it does appear to do. It is now being considered for FDA approval for those who are considered double-refractory to fludarabine and alemtuzumab (Campath), neither of which I have had yet -- but neither of which, the more I use chemotherapy of any kind, is going to work as well as it would have had it bee
n my first choice out of the box.

So welcome to the boxed-in world we CLL patients live in. What do you chose for your first act? How does that impact what you choose for your second? (And, transplant planners, how do those choices impact that third and probably final -- and I mean "final" in the hopeful "cure" sense -- act?)

Which brings us to another bit of recently-reported information, floating around the air like Mothra:

“First-line fludarabine not superior to chlor
ambucil in older CLL patients”

In a study of patients over age 65, the German CLL Study Group randomized 95 patients between fludarabine and chlorambucil.

Progression-free survival was similar in the fludarabine group (19 months) and the chlorambucil group (18 months); however, clinical significance was not reached. Overall survival was also similar between the two groups (46 months vs. 64 months), but again, clinical significance was not reached.

The bottom line is that fludarabine provided a m
ore robust response (as well as more bone marrow toxicity) but in the end that deeper remission didn’t mean the patients were living any longer, at least as of this writing. Keep in mind the OS non-difference between FCR and FC as reported by the German CLL8 group.

Of course, the trick is to track these things over a much longer time period, to see how overall survival of Regimen A vs. Regimen B goes on year after year after year.

Unless, of course, your CLL isn't giving you a decade or two to watch all the data dribble in.

Then you have to pick your monster and place your bet.

Hello Kitty, anyone?

The Hello Kitty Darth Vader, a sure sign that the end of civilization is near.

Sunday, August 09, 2009

The dog days of August

Anyone who has Googled "chronic lymphocytic leukemia" has run across references to the disease in dogs and, more rarely, cats. If you give Fido some chlorambucil, he goes on merrily chasing his tail, usually for a normal life span.

Recently I received a phone call from someone who read my letter to the local paper in which I explained that I have CLL and that I support
health care reform. The caller left a message on my answering machine. She said she supports reform also, and then began to talk about her dog, which was recently diagnosed with CLL. If it would not be a bother, she asked, would I mind calling her back and telling her a little bit about the disease and what might be done to treat her dog?

When Marilyn and I heard the message, our reaction was the same: laughter, of the disbelieving kind. I don't mind talking about CLL to fellow patients, or to my neighbors, or to a complete stranger who has some interest in the disease. But I'm not a veterinarian.

My gut level response, to my surprise, was anger. I love animals, and I like dogs, but I have seen too many friends and acquaintances die of this disease. I have seen too many struggle with impossibly difficult choices. For every great remission I have seen great disappointment. I have spent almost six years struggling with CLL, not always successfully. If I thought the last six years were bad, the next six promise to be worse. So pardon me if I don't have a lot of energy left over to counsel people whose dogs have leukemia.

Sometimes I think I'm being a little hard-hearted about this, but I cannot bring myself to call her back. I know she means nothing by it, that she's probably not aware that a CLL patient might develop some emotional baggage after awhile. Is she being a little insensitive? Or am I being oversensitive?

I empathize with her and her dog, but all I want t
o say to her is "Use your freakin' Google."

Am I right or am I wrong?

Saturday, August 01, 2009

The runaway shopping cart CLL fitness test

On Tuesday night we were at Bashas', our favorite local supermarket, which is built on a sloped lot. After we loaded the car with groceries, our shopping cart, to make a long story short, escaped. It was heading downhill, and at first looked like it would come to rest against a metal railing. But the gimpy wheel that had annoyed us during our trek through the store came into play, setting the cart on a subtle curve right toward someone's car, and it was picking up speed as it went.

It would not be right, I thought, to allow it to bang up someone's vehicle, so I took off after it, running as fast as I could. I caught up with it about three feet from the car it was heading for, which I saved from a scratch or a dent. I was not so lucky. As I grabbed hold of it, both it and I fell, me on my left side.

I bruised my shoulder, got some long scratches on my leg, and the bumpy asphalt was particularly unkind to the area just below and to the left of my knee. This was not helped by the fact that I was wearing shorts, leaving bare skin to come in contact with the ground.
I came away with a bloody sore about 2" by 2", part of it black.

Nurse Marilyn drove us home, I took a shower, and she administered Neosporin and a bandage to the wound. The next day we saw our primary care doctor, just to make sure everything was OK. This is where the CLL comes in, because if I did not have lowered immunity -- made worse by my neutrophils being at their nadir due to recent chemotherapy -- it's unlikely that we would have felt the need to be so cautious.

The doctor complimented Marilyn on her bandaging ability, and the black spot was determined to be asphalt, which had embedded itself in the skin, and which we were told would gradually work its way out as the wound healed. He was pleased to hear that I was on prophylactic Bactrim, which is one of the precautions I am taking while doing RCD (Rituxan, Cyclophosphamide, and Dexamethasone) therapy for CLL and AIHA (autoimmune hemolytic anemia). Apparently, Bactrim is used to fight staph infections, among other things. I was sent away with a clean bill of health, or as clean as a CLL patient with a bloody sore can get.

One of my first reactions to the incident, besides "ouch," was to put it in the context of CLL. It was as if I had been subjected to an impromptu physical fitness test: Did I have enough hemoglobin to run at full speed and tackle a shopping cart? Were my platelets numerous enough to insure proper clotting of the wound? Was my immunity good enough to avoid infection? Have my bones survived steroid therapy well enough to avoid breaking or fracturing when my 200-pound body hits the ground?

I was pleased to have passed on all counts, and to know that I can still endanger myself by stopping speeding metal objects.
After awhile, one learns to take nothing for granted about life with CLL, especially after having lived with periods when the disease, in the form of its AIHA complication, has impacted my ability to do things like I used to.

There is a fitness scale for cancer patients, called the ECOG performance status, named after the Eastern Cooperative Oncology Group. The scale runs from 0 to 5, with 0 being the best,
"Fully active, able to carry on all pre-disease performance without restriction." For most of my CLL life, I have been at that level. But the AIHA, with its red-blood-cell-destroying hemolysis, has put me at ECOG 1 or 2 at times. Two, for example, is ""Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours."

I suppose I am lucky that I am generally a 0, as the shopping cart chase demonstrated. I hope to avoid ECOG performance status level 5, which is described succinctly in the chart as "Dead." Those at level 5 don't put in much of a performance, evidently.

Saturday, July 18, 2009

There's no toxin like Cytoxan

Well, there probably is, but new lyrics are running through old songs in my post-chemo haze. “There’s no business like show business” is the tune, and I suppose that having had a round of RCD last week was getting down to business, so that’s why it turned into a rather annoying song looping through my head.

RCD is Rituxan + Cyclophosphamide (aka Cytoxan) + Dexamethasone, which is a protocol used by Dr. Kanti Rai and his group to combat autoimmune disorders, such as AIHA and ITP, in CLL patients. I, of course, am graced with the AIHA (autoimmune hemolytic anemia), a side effect of CLL gumming up the immune system, which periodically leads to bouts of hemolysis, in which macrophages destroy my red blood cells.

I had a variant of RCD for three rounds at the end of 2007 -- click on "AIHA" under "Posts by Topic" on the right for the whole saga --
which held me pretty well. But it did not involve the same steroid program as used in the protocol, which is 12 mg of dex given over seven days. I entered treatment then in a severe hemolytic crisis, made worse by the failure of my hapless Dr. O’Leary to see the depth of the problem, which necessitated a change of doctors in the middle of the red blood stream. Fortunately for me, my beloved Dr. Belle had just resumed her practice. For a couple of weeks there, I was on my own, doctorless, taking 72 mg of methylpredisolone daily in a desperate attempt to slow the loss of hemoglobin, which fell to 6.6 at its worst.

As we began the treatment
s — first with a little vincristine, which we quickly dropped due to side effects — we stepped down the methylprednisolone. The Cytoxan was doing the work.

Well, chronic disease is chronic disease. And like an annoying, insistent, door-to-door missionary, CLL is always capable of ringing the bell. It did that again shortly before Christmas 2008, which I wrote about here. I was put on 4 mg of dex, upped to 8 mg when that stopped working so well, to control the AIHA over the holidays, then given Rituxan and Cytoxan in January to nail it.

Readers know that Dr. Belle and I hav
e been experimenting with treatments since then, starting with the rather useless R-FFP. I noticed that my red counts were beginning to head south again at some point not too long after R-FFP concluded, so seeking to nip hemolysis in the bud, we did a week of pulsed dexamethasone (four days of 40 mg/day — quite a dose, but similar to what is given to ITP patients) and one round of standard-dose 375mg/m2 Rituxan. It did wonders, for a month, but while the numbers held, the nodes began to creep back. Then we decided to try more pulsed steroids -- this time, a gram of methylprednisolone by IV on one day, plus that standard-dose Rituxan.

The theory, which has been demonstrated in studies, is that there is a synergy between the methylprednisolone and Rituxan that seems to be more powerful than that between Rituxan and dex. But, then again, there's the real world of the particular patient. I have had a lot of methylprednisolone since
my AIHA diagnosis in March 2007, with the resulting time to grow refractory to it. We tried the pulsed dose recently to see how I would respond, this being a sort of trial run at the idea of maybe doing R-HDMP.

Well — surprise, surprise — just a couple of weeks afterward the red counts began to show a subtle drop again, I was alerted to this by more-orange-than-average urine (hemolysis warning sign No. 1) that I have described in the past. The conclusion: methylprednisolone is not going to do much for me, and neither is Rituxan along with it.

The RCD protocol no doubt involves the “D” for a reason, and this time we followed it close to religiously, other than my starting the seven days of dex a little ahead of schedule to keep the hemolysis in check over the weekend. I am pleased to report that Friday’s CBC shows a remarkable recovery of the red counts — heck, my hemoglobin went from 12 to 14 in a week, and the overall RBC jumped from 3.91 to 4.43.

Some conclusions

Part of the purpose of this post, which I am dashing off during what is laughingly referred to as a “day off” around here, is to put forward some insights on steroids, AIHA, and treatment based on my experiences. They come with that anecdotal warning, as well as that internet adage, YMMV:

AIHA patients often face a progressive order of attempting to control the condition. First steroids are usually given, but those can cease to work. Rituxan may be next (or may be given with the steroids), and th
at can cease to work. At that point, you’re looking at heavier-duty chemo. R-CVP is similar to RCD but involves vincristine, which can lead to neurological problems and which by my experience should be avoided unless truly necessary. RCD is gentler and (for me, so far) quite adequate to the task.

It does involve Cytoxan, which is a venerable old toxic drug used in many cancers, and which may be somewhat better than average at getting at 11q-deleted CLL, which I have. Cytoxan (good PDF here, and yes, the more powerful the drug the more fire you play with; this beggar can't be as choosy as he used to be) gives me few side effects, at least that I can see or feel anyway. Lord knows if it's setting up some mutagenic condition that could lead to another cancer, or to further disease resistance on the part of my CLL clones, but remember that line about beggars.

I don't lose my hair, but I don’t have much left to lose anyway. The drug tends to destroy rapidly-reproducing cells, taxing the stomach lining, but it has not given me nausea, only the desire to eat bland food for a few days. I do get GERD
, which I find to be easily controlled with Prilosec OTC.

Speaking of food, with all those steroids as well as the Cytoxan, be aware of your glucose. I avoid sugary, carby things as much as possible during the treatment window and I have no hint of diabetes. Still, my glucose, when tested, goes higher than the norm.

I also get more easily fatigued by the changes the drugs wreak in my body, especially when Cytoxan is part of the equation. I have lost at least 15 pounds in a week, much of which appears to be lymph node weight. (People say I look wonderful after chemo.) The neck nodes, which were brought down nicely by the pulsed steroids without the Cytoxan, were brought down much more dramatically with the Cytoxan. I have a lot of abdominal nodes, and for the last couple of nights have been able to sleep comfortably on my stomach — a sign that progress has been made in these unseen areas, too.

Because of tumor lysis — C
LL cell kill, with all the dead cells making their way through your kidneys — it is important to stay well hydrated. I drink at least a gallon of water the day before, of, and after my treatment. (And I use allopurinol -– a commonly-given drug that helps control uric acid -– a few days before, and continue it as long as the cell kill remains.) Then I keep on drinking as much water as I can stand. Even with all that, Friday’s blood test showed my BUN was high, not untypical considering all the cell-kill my body had been through.

The water also helps protect your bladder from the Cytoxan, and you should go with the flow, pee whenever you need to just to keep the stuff moving through. Watch the serum sodium results on your metabolic panel, as well — this can dip, so you may want to consider drinking salty water or eating salty foods for a week or so after treatment.

Keep in mind also that steroids are immunosuppressive and that Cytoxan is immunosuppressive, so staying on prophylactic meds -- acyclovir, diflucan, Bactrim -- during this period are part of the tools of the trade of the appropriately cautious doctor and patient.

RCD (dex pills in photo below) works for me where Ritu
xan alone, and Rituxan with pulsed methylprednisolone (HDMP), do not.

I have been around the steroid block enough now to have some feel for how I react to them. Steroids are excellent though transient reducers of lymph nodes. But they come with enough bad side effects — osteoporsis for one — especially when given in smaller, long-term doses, that they should be used sparingly. (Big, pulsed doses appear to be safer, based on information from UC San Diego and elsewhere, but that's still powerful stuff going into your veins.)

I find that node reduction in steroid-Rituxan combinations still rests largely with the ability of the steroids. (The Rituxan helps more with the cell kill, providing a somewhat deeper, though still shallow, remission.) Once you add Cytoxan, the game changes, at least in me. The nodes reduce as much again as before, and the remission lasts far longer.

Another thing I have noticed along the way is that the mental effects of the 'roids (such as sleeplessness) seem more pronounced when I am on smaller doses than when I have undergone the big pulses. Methylprednisolone at 72 mg and less tended to make me worry things a little, but not at 1 gram. Forty milligrams of dex over four days had the mental effect of drinking water, but give me 12 mg and my brain shoots into overdrive, getting very detailed about things, and I have trouble sleeping. (It should go without saying that dose equivalencies among steroids vary greatly -- this converter can come in handy.)

I expect to be undergoing more rounds of RCD, then perhaps to have a CT scan to see where the nodes stand abdominally, where they are worse than neckly and underarmly, to coin some medical phrases.

Right now I look like a slimmed down picture-of-health, ready to absorb all those laudatory comments from friends and acquaintances who wonder what kind of a marvelous crash diet I've been on.

Saturday, July 11, 2009

Living the not-so-good life in Sedona

Our little city of Sedona, nestled amid the red rocks of Northern Arizona, is a resort community and tourist destination. A lot of people retire here to live the good life, or choose to live and work here for the same reason.

It's reasonably affordable, as such places go -- unless you come down with a catastrophic illness and are subject to the whims and foibles of our health care system. I am not talking about myself here. I am talking about a couple in town who lost pretty much everything in a futile attempt to battle the wife's colon cancer. This was reported recently in our local newspaper, the Sedona Red Rock News. Here's a link to the story, entitled "Health system fails Sedona couple." Here are some excerpts:

It wasn’t long before all of the DiMarcos’ days were consumed with medical appointments, arguing with insurance companies and pleading for help from state agencies.

By 2007, their lifelong savings had
dwindled to nothing, exhausted by treatments and drugs deemed ineligible for coverage by their insurance company. With no money left, Joseph turned to credit cards to pay for hotel rooms near hospitals, for co-pays and for pain medication.

. . . In spite of hundreds of thousands of dollars of tests and treatment, painful procedures and mind-numbing drugs, by 2008 Andrea’s doctors held little hope for her recovery and she was referred to RTA Hospice and Palliative Care in Sedona. She passed away two months later.

Joseph is left with the memories of a woman he describes as his soulmate, a twin flame with whom he wanted to grow old. He is also left with a mountain of bills, having to choose which one to pay each month.

In the latest print edition is another story
(not online), this time about a patient with heart problems who faced the unfairness of the system first-hand. This involves the "churning" of insurance applications, in which private insurers look for an old condition or treatment you may have forgotten to mention and use it as an excuse to cancel your plan rather than pay for the care you desperately need.

My point here is that in any community -
- even one of 15,000 people -- there is story after story like this. Health care reform is needed not only for the 50 million uninsured, but also for the many millions more who are insured, only to find that the system fails them when they need it most.

Here's a letter I just wrote to the editor of the News:

I’d like to commend the Red Rock News for its recent series of articles on how failures in our health care system have caused heartache and pain for local residents who are the victims of cancer and other serious diseases.

I am one of those stories. In 2003, I was diagnosed with chronic lymphocytic leukemia. Mine is a fairly aggressive form of the disease and I have required several rounds of chemotherapy. Fortunately, this has been covered by my health insurance, a state-sponsored program for small businesses. But the plan has its limits. It specifically excludes adult stem cell (bone marrow) transplants. I am 52 years old and the exper
t doctors I have traveled to see out of state (at my own expense, since my plan only covers a limited in-state network), have told me that I am unlikely to see 60 unless I get a transplant. These can run upwards of a million dollars out of pocket, well beyond my capacity to pay.

As you might imagine, private plans that cover transplants want nothing to do with me. Unless there is health care reform in Washington that requires all insurers to take patients with preexisting conditions, I face a bleak future.

I am all for keeping private insurers, but I also strongly favor a public option. Some mechanism has to be put in place to keep private provid
ers honest, as your most recent article about the “churning” of health care applications demonstrates. If people cannot rely on their private insurance in a pinch, then they deserve an option where care is truly guaranteed.

To those who were recently seen protesting here against “Obamacare” and who argue that they don’t want the government managing their health care, I have this to say: What is so offensive about creating a system that preserves your sacred private insurance but also gives people like me a chance to receive life-saving care? Is it really preferable to have penny-pinching private insurance bureaucrats finding excuses not to give you the procedures and drugs you need? I’d take a government bureaucrat any day -- I’ve
been dealing with them at the state level for years -- since they don’t have that vested interest in finding ways to deny me, or my doctor. Finally, if you really hate “socialized medicine,” then give up your Medicare coverage on principle. I’d gladly take it.

David Arenson


Counties in blue have some sort of universal health care system. Countries in green are trying to institute one. Countries in orange -- Iraq and Afghanistan -- have universal systems instituted by the United States after they were invaded. Perhaps we have to declare war on ourselves to get universal care?

Sunday, June 07, 2009

Two thumbs down on Rituxan + fresh frozen plasma

I came. I saw. I wasted my time.

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

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

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

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

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

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

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

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

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

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

Saturday, May 23, 2009

Beyond living "la vida leuko"

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

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

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

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

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

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

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

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

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

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

Wednesday, May 13, 2009

Might as well jump (?)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Saturday, April 04, 2009

Rituxan + fresh frozen plasma

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

Thursday, March 12, 2009

The news hole

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

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

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

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

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

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

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

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

A tip for fellow remodelers

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