Endgame?

Too soon to declare victory.

But since I started acupuncture treatments, 12 days ago, I've had no headaches to speak of. (Well, I did have one, but it felt more like a hangover from taking a muscle relaxant at 3:30 AM.) Tension in my face and jaw slowly diminished. That's still hanging around, but at a low level, doesn't distract me much now and seems a bit lighter every day. Teeth mostly stopped hurting, too.

I had three followup appointments, 3-4 days apart. Yesterday the acupuncturist declared my case closed, except for a tuneup in 2 weeks.

Also, no drugs at all now, except nortriptyline for chronic insomnia. (If you read the link, don't freak out — my dose is only 15 mg, not enough to trigger the increase in suicidal tendencies that can accompany this drug when it's used as an antidepressant at 50-100 mg. And I had the insomnia long before HCL.)

One of my colleagues wrote:

I know about headaches, had them for 1.5 years every day. It was hard; I even talked to my own headache, as if it was a person controlling me. At some point, however, it disappeared, slowly. And when it was gone, I even missed it, strangely enough. I asked where are you? Of course, it was a blessing to live without it again. I hope you will find the same grace. I wish you love, strength and courage.

I know what he means. Mine lasted from the beginning of December until the middle of March. Three and a half months. You have no idea how good it feels to be able to just say Fine, thanks when somebody asks me how I'm doing. Pain makes very boring conversation.

Yesterday I spent 7.5 straight hours in social situations — meetings, a talk, a dinner. Wasn't sure I'd make it, but I did. Three weeks ago I couldn't go out at all, could hardly talk to my family, had to keep going off to lie down and try to relax my face. The slightest facial expression felt like the Nazi dentist from Marathon Man testing his drills on my head. When that's happening you think it will never stop. Thought I'd ruined my teeth. Started imagining living with dentures at age 50. Began contemplating a permanent headache, daily pain, a lifetime of pureed food — somehow accommodating to that. Somebody else I know has had more or less constant pain for a decade or so, from neck and back problems. I can't imagine how she survives it — much less taking the time to read this blog and write me sympathetic emails. Where does that come from?

The last few days have been almost like normal. Almost like before leukemia. Not quite. That one's not so easy to forget. And I'm still a bit nervous about the headaches coming back. If I go a month without them, I might get ready to drop my guard.

Acupuncture

The week that followed my previous post consisted mainly of me lying in bed moaning like a dying warthog. Headaches from the third circle of hell. My temples screamed. The slightest facial expression made my jaw muscles clamp down so tightly I could hardly open my mouth. My teeth ached constantly, moving every couple of hours from one tooth or area to another just to keep me on my toes. My diet consisted entirely of soup and fruit smoothies, though even the soup made my teeth hurt. Vicodin and muscle relaxants would knock me out for a while, but it wouldn't be long before I was back in the inferno.

Then, last Thursday, I went to see an acupuncturist.

I'd tried this a few weeks earlier with a different practitioner, but the effects were minor at best. Then the guy tried to sell me on a weird enzyme-nutrition theory, so I didn't go back. This time I went to someone I'd seen seven years ago, for hip muscle spasms.

Having lived in Santa Cruz, CA for 9 years, I'm not a newbie. You can get treated by students at a local acupuncture school there for not very much money. I probably did 15 or 20 sessions altogether. The complaints I went in with were ones that probably nobody could do much about: chronic knee pain, most likely from a torn meniscus, and tinnitus (ringing in the ears) thanks to my previous life as a rock musician. The treatments didn't fix my problems, but I enjoyed them. Often I'd fall asleep on the table.

Two conflicting thoughts always run through my head when I do this. One is placebo, placebo, placebo. He's creating an atmosphere, reassuring me, pulling on the power of my desperation and my hope. And now I'm lying here relaxing for half an hour looking like a pincushion. Of course I'm going to feel better, but nothing's really happening. The other thought is this technique works directly on the nervous system. Western approaches treat nerves with drugs that affect the entire system all at once, but acupuncture acts on individual nerves related to specific sensations. Of course its effects are real.

This time, the effect was so dramatic that I simply can't believe it was placebo. I went into the office with a splitting headache, pain in my teeth, hurting so much I wanted to curl up and die. No bullshit, no explanation, no pep talk; Brodie just said let's see if we can get you feeling better and went to work. The first needle went into the top of my left foot, but I felt it mainly in my jaw. Most of the needles went into my hands and feet; a few into the sides of my head and my ear. This was a different pattern from what the other acupuncturist had tried (and I didn't feel much from his needles). I lay on the blissfully warm heated table for an hour, and all the tension and the pain simply melted away.

I left the office with no headache at all. Over the course of the day, the pain in my teeth gradually diminished. When I woke up the next morning that pain was gone, for the first time in 3.5 months — and it has not returned. Tension in my jaw muscles did continue, coming in waves lasting an hour or so. But though this got quite uncomfortable and distracting, it was not actually painful.

Felt the beginnings of a renewed headache on Monday, plus more jaw tension. Had another treatment and again, the next day was a very good day, no pain and much reduced jaw tension. I'll do this again a couple of times and see where it leads.

Now, I'm not a controlled experiment. Who knows if this would work the same way for you. I'm blasting away with every weapon I can think of, all at the same time, including muscle relaxants, ibuprofen (for inflammation), nortryptilene, self-hypnosis, etc., and so would you if you were me. But following the acupuncture I've tapered off the ibuprofen to just 4 pills a day, and mostly off the muscle relaxants too. No Vicodin, either.

Nothing else I've tried has been nearly so dramatic. It was, in a word, like magic.

While little is known about the mechanisms by which acupuncture may act, a review of neuroimaging research suggests that specific acupuncture points have distinct effects on cerebral activity in specific areas that are not otherwise predictable anatomically. — Lewith et al., in Evidence-based complementary and alternative medicine: eCAM 2:3 (2005), 315-9.

Head case

So I've made my decision. Or maybe I should say that now a decision seems possible, for the first time. I'm going to stop worrying about HCL. Whatever happens will happen. I can't control it, and grinding away won't help. So stop.

I studied the beautiful martial art of aikido for 13 years, got a black belt, taught it at Apple Computer for several years — would still be doing it if my knees hadn't had enough. I've practiced yoga for 24 years, almost half my life. These are intensive physical disciplines requiring enormous, extremely precise control of the body. Every muscle, every tiny movement, the expression on your face, the motion of your breath are all part of the whole. You have to master all of it. The miracle is that you can.

Yet the further you go, the more you realize that controlling the body is merely a baby step toward something much, much harder: controlling what happens in your mind. In aikido, it's controlling fear and reflex; staying relaxed, easy, joyful with an attacker bearing down on you, eyes wide open and aware while you're spinning, rolling, flying upside down. Blending with the energy of an attack, channeling it into smooth, clear motion.

In yoga it's ending thought, in savasana (corpse pose). You just lie there on your back, resting, with your arms and legs splayed out and your eyes closed. Sounds easy. But the point of the pose is to clear the mind of thoughts, simply inhabiting the body, feeling the breath rise and fall. No past, no future. Only the present moment, here, now.

Eventually you learn: savasana's the hardest pose of all. Harder than 10-minute headstands, back bends, splits, extreme contortions of all sorts. In those poses you can't help but be in the present. You're concentrating so hard, against so much powerful physical sensation, that you almost don't have a choice. (Though even here your mind can wander.)

Worrying's the same. You know it doesn't do any good, but you keep right on going anyway. You're addicted. You decide to stop, but your vigilance gives out after 2 minutes and once again you're fretting away, mainlining anxiety, doing your drug. Your six-blade knife, do anything for you. You worry in your sleep, while you're working out, at the movies — even, secretly, while saying goodnight to your child, whispering to your partner, laughing with your friends. And you just can't stop. Not under your control. Maybe you blame it on somebody else, usually the person who loves you most. Maybe you blame yourself. Either way, now you're worried about worrying.

In my case, I can stop the conscious thoughts to some degree. But these infernal f-ing headaches just keep hanging around, stormclouds on the inner horizon, an embodied form of worry. The muscles in my face seem to be in permanent spasm. Hard little knots of fear, bundles of pain. Here's a partial list of what I've tried:

• Self-hypnosis recordings on relieving TMJ and headaches
  
• Binaural beat recordings
• Hot tubs
• Saunas
• Professional massage
• Self-massage (ma roller, fingertips)
• Yoga
• Inversion sling
  
• Moist heat pack
• Cold pack
• Ibuprofen
• Vicodin
• Ativan
• Alcohol/no alcohol
• Caffeine/no caffeine
  
• Inane TV shows
• Trashy mystery novels
  
• Intermediate bite splint (thin, hard)
• Soft bite splint
• Books on trigger points and TMJ
  

All this, but the headaches and the teeth-clenching still go on. Anything that induces facial expressions — basically any social interaction, even phone calls — ends with the sides of my head on fire, flaming golf balls wedged in my cheeks.

I know some people live with headaches forever. But now that the HCL is (temporarily) behind me, I'm determined to wipe them out. Maybe this will just happen, slowly, as an unconscious process. Right now I'm trying a week of heavy-duty ibuprofen, vicodin, muscle relaxants, bed rest, on the theory that if I can knock out the pain long enough maybe the muscle spasms will ease. Various appointments with specialists are pending, but I don't have high hopes. Ultimately this has to come from within.

It's going to take mind control. And that is just, basically, incredibly hard.

Yo-yo

• Hemoglobin 13.3 (WHO normal 14.0-17.3) — normal by UM standards
  
• Absolute neutrophil count 4.1 (normal 1.4-7.5) — NORMAL
  
• White blood cell count 5.1 (normal 4-10) — NORMAL
• Platelet count 218 (normal 150-450) — NORMAL

Wow. I've never been through a bounce like this one. I feel like a human yo-yo.

Saw Dr. B today. His news is nowhere near as bad as they'd told me a week ago. In fact, the news is great — not perfect, but great.

So. The morphology — visual examination of my bone marrow biopsy, under a microscope — had revealed a small nodule, entirely normal in a 50-year-old guy. They stained the sample to find out what was in it. One of the stains showed CD-20, the cell surface protein that's typical of hairy cells. They determined that 5-10 percent of the bone marrow space consisted of CD-20 positive cells. That's what Dr. B's PA reported to me as "5-10 percent hairy cells."

For whatever reason (who the hell cares, now), she misinterpreted this result. CD-20's expressed on all B-cells, including the normal ones. So the 5-10 percent figure says exactly nothing about the percentage of hairy cells in my bone marrow.

What about the flow cytometry, the laser-based protein marker detector, far more accurate than morphology? On the flow, things looked, in fact, PRETTY DAMN GOOD. Less than 2 percent hairy cells! Yow! Dr. B said this is somewhere between a complete remission and a partial remission, in other words, a very very good partial remission — not at all what I'd been living with all week. Boing-a boing-a boing-a; this time the bounce is up. Sometimes you're the bug, but sometimes, sometimes, you get to be the windshield. Splat.

On top of that, my blood counts look great. Low lymphocytes (0.4), but we knew that. Almost normal red cells (4.43; normal is 4.5). Hemoglobin at 13.3, which UM counts as normal. Probably both of those will still rise for another week or two. Everything else well inside the normal range. I haven't seen a test like that in years.

What to do next? Dr. B's answer: nothing. No more treatments. Watch and wait. He calculates that the risks of rituxan aren't worth the additional benefit, especially because nobody's really sure, yet, whether there actually is any additional benefit from 2-CdA + rituxan. Most people in my category typically go years, even many years, before a remission (though some don't, and I'm mindful that I could always turn out to be in that camp).

We ended up leaving it that I'll go back for one more bone marrow biopsy in 3 months, see where I stand then. (Don't have to, but I want to, for psychological more than for medical reasons.) It's even possible that by then the 2 percent will drop further, though it could also go higher. But unless it really shoots up, I'm set for a while, and convinced that waiting is the right thing to do.

More later, after I celebrate. Yo-yo.

There is a girl in New York City
Who calls herself the human trampoline
And sometimes when I'm falling flying
Or tumbling in turmoil I say
Whoa so this is what she means...
She means we're bouncing into Graceland

Decision theory

To tux or not to tux: that is the question.

Rituxan (trademark name; generic is rituximab) is a monoclonal antibody. "Monoclonal" simply means that the antibodies are identical (cloned). These artificially produced antibodies bind to the CD-20 protein complex on the surface of B-cells, including hairy cells. This dupes the immune system into thinking those cells are foreign, so it attacks them, with the same responses it would deploy against invading bacteria.

The drawback: rituxan can't discriminate between normal B-cells and hairy cells. It's genocide; the stuff just kills them all (or rather, it paintballs them and leaves your own body to do the dirty work on itself). Then the body grows new B-cells. You hope, you pray, that the new population doesn't include any hairy cells, or at least not so f-ing many.

In HCL, rituxan doesn't work very well all by itself. 8 weekly doses does markedly better than 4, but the response rates using rituxan alone, in previously untreated patients, are nowhere near as good as 2-CdA. But what about a combination of the two?

Those of you who've followed this blog may remember that early on, I considered enrolling in a clinical trial now underway at MD Anderson in Houston. They're testing a regimen of 1 week 2-CdA + 8 weeks of ritux starting 28 days later. In 13 patients treated with this regimen,

the CR rate was 100% with eradication of MRD (minimal residual disease)... in all but 2 patients after completion of the sequential therapy. No additional toxicity was observed with the combination compared with historical experience with 2-CdA alone (Hematol Oncol Clin N Am 20 (2006) 1125–1136).

That sounds pretty exciting, but it's only 13 people. Statistically, 2-CdA alone would have produced 9 or 10 CRs in a group that size anway. Still, if this trial works out, this regimen might become the new front-line therapy in a few years. If I do 8 weeks of rituxan now, my treatment would be almost clinically equivalent.

Let's be realistic here: this is not aspirin. My HCL friends haven't experienced serious side effects, apart from the few hours during and after the infusion (see Experience). But bad stuff does happen. Patients have died from cardiac arrest and kidney failure. A small number — all of them already suffering from lupus — came down with progressive multifocal leukoencephalopathy, a horrifying virus that kills brain cells and, eventually, you. You can get pulmonary toxicity and other nasty effects. However, most of the patients who've used this drug were being treated for other leukemias and lymphomas (not for HCL), so they were a lot sicker than I am and thus more likely to suffer side effects. Still, the reality of risk has to be faced. (That sentence sounds a lot nicer in passive voice.)

So here's my decision theory, so far.

Reasons to tux:

• A good-to-excellent chance of achieving complete remission (less than 1 percent hairy cells).
  
• A fair-to-good chance of achieving complete molecular remission (no detectable hairy cells).
• If I'm gonna do it, now's the time. Ritux doesn't do well once the population of hairy cells gets larger. If I wait, I'll have to do another round of 2-CdA before I can get much benefit from rituxan. On top of that, I have the flexibility in my life and schedule right now to do the treatment without drastic effects on my job and my family.
  
• A fair-to-good chance of a CR lasting 5 years or longer. New, better, more targeted drugs might be ready by then. If they are, I might not have to drag my body (and my family, and my friends, and you) through another round of 2-CdA.

Reasons not to tux:

• In HCL, the relationship between the degree of remission and its duration — the time until symptoms reappear — is not straightforward. I'm at 5-10% hairy cells now. It's entirely possible I could stay this way for 2-4 years, or more, without treatment. Conversely, even if I achieve a complete molecular remission, the HCL could still come back in less than 5 years.
  
• Immediate risks from rituxan infusions.
• Longer-term rituxan side effects. I'm still coping with daily post-2CdA headaches (see my blog entries from January). Headaches are a low-grade side effect, not life-threatening; the medical literature barely tracks them, so there's no real way to know if the 2-CdA might have caused them. (In higher doses than I received, 2-CdA is neurotoxic, hence my suspicions.) Rituxan might make them worse, or slow my recovery, or both. Can't know in advance.
• What WAID and John said, about not doing a treatment just to get nicer numbers, and about handling HCL as a chronic disease.
  

Seeing Dr. B tomorrow. My main questions for him: what's your clinical experience with rituxan? Side effects? What's the timeline for the other drugs now under development? What do you think of their chances for success?

And most of all — if you had HCL, what would you do?