Glad to be Wrong!

Scientists are extremely opinionated, despite the occasionally-awkward public attempts to appear to be otherwise. By "opinionated," I mean that we passionately believe something to be true despite lacking proof.  But, as scientists, we want to do the arduous work of designing experiments that would confirm or deny our beliefs. (By the way, in my experience, and able to offer no explanation, scratch a mathematician in particular and underneath you will find a lover of the arts, including poetry. Among the group you will find a fair number of amateur actors. Mathematicians are by far the most emotional people I know.)

On the other hand, scientists are readily-adaptable people. When confronted with a truth that belies their belief, they adopt the new truth as if they had never thought otherwise. Their beliefs change when the facts change, and so do the questions and experiments that subsequently arise.

I passionately believed that my cancer had become resistant to steroid treatments. Not only are steroids the most effective treatments we have (as single agents and in combination with others), but not responding to them is a horrifying prognostic indicator. I've known some who were resistant to steroids from the beginning: they are all dead. When the disease evolves to that point, nothing further is going to be easy. It's a definitive signpost of the endgame.

I had evidence but not proof. When I stopped responding to DVD-R, which includes just about everything we've got including dexamethasone, our strongest steroid, I thought I saw the signpost. That was last May Day. I've had no other good news since July.

But I wanted proof. I had two reasons. Steroids eventually destroy the adrenal cortex, which leads to a life-long need to take low dose steroids. Secondly, high-dose steroids drive most of us crazy to some degree or another, having a profoundly negative effect on quality of life. Quality of life matters, sometimes more than length. I wanted to get off steroids completely, and if they don't work for me, why am I hammering myself with them?

The experiment is easy. Go up to the most-effectively known treatment schedule for steroids for a week or two, then measure before starting any other chemotherapeutic regimen. My cancer number was an astronomical 304. If it went up or stayed the same, it was proof that steroids were of little use to me and I could stop them. My anxiety came from wondering just how much higher the number would go before starting the arsenic.

Instead, as you can see from my partial chart, the number fell by more than 2/3, the most dramatic drop I've ever seen, to 102. The new truth? Weak steroids have no effect on me, and my dose/response effect is not linear (meaning, there seems to be no smooth relationship between response and dose level). Instead, there's a threshold that must be met before seeing this kind of response. The response may or may not be linear with greater or more frequent doses than those effective at the threshold.

One nagging failure of design was that the experiment lasted only one week and confused dosing. On Tuesday, I took 40mg of dex orally (the largest common oral dose we use), and on the following Saturday and Sunday, one dose of 20mg each day (two days a week of 20mg each day is now a common dosing whose effectiveness has not yet been disproved: there is some evidence that higher or more frequent doses produce poorer outcomes).

On the other hand, as a scientist/patient, and having received the first morale-building good news in months, I am filled with hope. Many ugly likelihoods are gone. I have NOT seen the signpost pointing to the end of usefulness of steroids in my disease. I WILL likely make it through January when it is my intention to undergo a potentially life-saving reduced-intensity allogeneic transplant from a matched but unrelated donor (it can also kill me). If the transplant happens, the most likely outcome is at least a few more years of life (albeit with some annoying but likely complications).

Yeti and Me

Yeti: 1992–2009

Ivonne summed up Yeti better than I could, in a single sentence: Yeti was all about love. He greeted every visitor, remembered them, had the loudest purr of any cat I've ever known (as a vet tech once said, "He has a good motor"). Visitors who didn't love, or at least tolerate, cats, were not welcome in my house.

He could also hug you with his arms, and squeeze your finger with his paw.

He was my best buddy for nearly eighteen years. Every morning, I would awaken and walk down two flights of stairs to make my coffee, toast my bagel, and fetch my newspaper. Every morning for many years he would beat me to the first floor. The one time I beat him he went to the vet within the hour.

He always knew when I was feeling poorly, such as during the eight months I spent in a hospital bed and wheelchair with round-the-clock nursing as the result of a motorcycle accident. He was nearly always beside me on the bed, touching. He had to give up his usual duties for the duration.

Yeti had many duties. One involved periodic inspection of kitchen and bathroom cabinets. He would point his nose at one of interest and stand completely still until I opened the door so that he could go in, look for deficiencies (or mice) and correct them.

The yard was his outside territory. He like to go out after breakfast, when I would fetch my newspaper, and circle the property, looking for interloping cats, rodents, or anything else of interest. When I would call him, he always came running. Sometimes he would stay out all day and roam quite far, but he was always home at 4:30 sharp because he had an internal, self-adjusting, infallible kitty watch. It usually took him but one day to adjust to daylight savings time.

I fed him at precisely at 4:30 (that way, I knew he would always be home before dark). Even last week, if you didn't know where he was or what time it was, at 4:30 he would find you, have dinner (always meat) and take a nap. (He preferred raw meat, which required excursions to an expensive, magnificent meat market.)

Yeti was a pedigreed cream-point Himalayan. Say what you will about purebreds, they have a LOT of personality. I loved him beyond all reason. Every day of his life I cleaned around his eyes and nose (Himalayans, with their pushed-in noses, usually collect crud around their eyes). At first he didn't like my doing it, but later decided that my cleanings were a kind of love, so he purred and didn't object. I believe that he felt that no matter what annoying or painful thing I had to do to him (like give him a bath), it was because it needed doing. Amazingly, he was completely immune to fleas. Cats don't get better than that.

At one point, I hoped, with my weak knees, I would die before he did. I couldn't face the the possibility of losing him.

These last two years have been hard. He developed arthritis in his rear hip joint, which caused him to slowly lose feeling and control of his hind legs. One by one he had to give up things he had done for years, like going outside. I remember the last time he successfully jumped up on my bed, and the last time he tried (and failed). He lost most of his hearing. I remember when he stopped being the lion king who ruled over his two young female kittens (also Himalayans). It became harder and harder for him to balance on his hind legs, although only last week he made his last trip up the stairs to sit in my lap, purr, hug my arm, and have his eyes cleaned.

He wasn't suffering pain: he was losing hind-leg sensation. For the last few weeks he had difficulty climbing over the low-ridged catbox and had accidents in the laundry room. But he was still there, still my Yeti.

But not last Monday. I don't think he could stand at all. For the first time I saw suffering; not of the pain kind but of bitter frustration of loss. He had been reduced to doing circles trying to gain enough leverage to stand but couldn't.

It wasn't the best of times for me, either. My cancer numbers were rocketing dangerously out of control, I had no food and plenty of clear slop to drink for the day prior to my endo/colonoscopy Tuesday morning, was flying on steroids, and was scheduled to start Arsenic on Tuesday afternoon (not an easy course of treatment to accept). But I awoke at 2am Tuesday knowing that Yeti's time had come. I asked whatever gods may be for one more day, one more rally, because I was at the end of my rope. I wanted one last day to hold him, clean his eyes, and listen to him purr. It was not to be.

One glance as I flew out the door to go to the hospital confirmed everything. I couldn't think about that. I had to go. When I finally game home, he was in a coma. Ivonne wrapped him in towels and brought him to me. I spent more an hour holding him. I gave him couple of syringes of water, but there was no reaction. His eyes reacted to light, but I don't think he actually woke up. Maybe the vet could rehydrate him and bring him back, but he had nothing left, really, to come back for.

I have no words for how difficult it was for me to accept what I had to do, especially considering how weak I was. But I took him to the vet and asked her to help Yeti pass over. He died in my arms, never regaining consciousness. Later this week he'll come back to me in a cedar box. I intend that he shall share mine, when the time comes.

I grieve for me, too, selfishly. Over the years, like Yeti, the cancer has forced me to give up so many of my routines and duties, starting with my career eleven years ago. Only last year I was weight lifting at the gym two or three times a week. Emotionally, I haven't given that up, although physically I haven't been to the gym this year. I gave up most chores. I hire people to do work around the house I would have previously taken pride in doing myself.

The amazing thing, the most improbable and clearly miraculous thing that has ever happened to me, was finding and falling in love with Ivonne. The chances, given my situation, of such luck, were vanishingly small. Our love makes up for so much that I have had lost!

Still, I gave up most concerts and movies (now Ivonne and I watch Blu-ray DVDs with 7.1 audio instead on a magnificent 62" screen); ditto fancy restaurants; most dinner invitations. Lately, I haven't had enough energy to work on the serious piano pieces I studied intensely earlier in the year (e.g., Brahms Gmin Rhapsody, Op. 79, #2). I spend too much time in bed, reading. I don't cook as often or cook things requiring a lot of time in the kitchen. I don't shave or bathe often enough.

I did manage the two biggest projects since my retirement from work in 1998: the wedding, and managing the amazingly complicated and expensive process of making my bride, Ivonne, a permanent resident of the United States. It took three months of complicated study and ended up as five petitions, two-sided, plus supporting documentation one and one-quarter inch thick. Someday I'll write about it because it's a process, if you are unfamiliar with it, as hateful and adversarial as you can possibly imagine. Welcome to America!

In the end, I think I was grieving for both our losses, Yeti's and mine. Having to give up big chunks of our lives was bad enough, but at least his final decline was quite rapid and seemingly painless: will mine be as well?

Bye for Now

And Away we Go!

The squiggly red line, which approximates the number of plasma cells in the body, both normal and malignant, has reached the stratosphere. If we can't stop its rise, it will stop mine. It rose seventy-three points in one week. Malignant plasma cells crowd out what I need to fend off infections. The value should be 1.94 or less. It is now 304.

The time has come to make sure that my emergency go-to-hospital kit is properly packed (warm socks, pajamas, underwear, robe and slippers, ordinary meds, toiletries, Marinol (synthetic marijuana), cell phone and other chargers, computer cables, hard New York Times crossword puzzles, pencils, journals, a huge book I can read for weeks, etc.). Also it is time to activate wireless broad-band access for the laptop (so I can watch anything I've recorded on TiVo at home — see Slingbox).

I need to keep going until January, when there may be the life-saving possibility of a reduced-intensity allogeneic transplant from a matched, unrelated donor. At this point, the staying alive bit is not a sure thing. Until then, I have to hide from sick people (except for Ivonne, who, with near-perfect timing, has come down with a belligerent cold), and the cancer has to be relatively kind to my bones and organs.

There never seems to be enough time for certain important things, yet I realize I've been blessed with a great time to re-do my Last Will & Testament! Tag family heirlooms with where I want them to go! Videotape final curses for my heartless children!

On Wednesday I took a huge dose (40mg) of steroids (dexamethasone). Saturday & Sunday, the steroids at half-dose will be repeated. Then blood tests on Monday. Throw in a colonoscopy and endoscopy Tuesday morning (I'm looking forward to awakening at 4:30am to drink a half-gallon of hog slop). Then, on Tuesday afternoon, the poisoning with arsenic trioxide, velcade, & vitamin C (IV) will begin, and will be repeated on Friday if I survive. (The regimen is called ABC.) Oh, and Medicare might not pay for it, so it might cost me $2K/week to experience element 23 of the periodic table. For those of you obsessed with "eating healthy," I would like to point out that arsenic is thoroughly natural and is probably available at Whole Foods.

Please Pass the Arsenic

In the eleven years I've been fighting multiple myeloma, having a long-term plan has let me live a relatively normal life. In the beginning, I didn't know what was important, so I studied all aspects of the disease. Back then this kind of study was quite difficult because the Internet was still young — the only way to get a journal article was to xerox it at a medical library.

But as time passed, I was able to narrow the focus considerably. I realized I needed to know only two things: first, how to read my labs so I would recognize when a change in treatment is needed; secondly, the set of available treatments (e.g., principal drug, manner and frequency of administration, likelihood of success, side effects and possible complications) and procedures (e.g., autologous transplant, allogeneic transplant, radiation). Planning develops the rationale that helps to determine the order in which the various treatments should be tried. (Determining the best order is a matter of considerable medical controversy.)

The final element of planning is to determine empirically the maximum safe interval between measurements of disease activity. I can then put the date of my next set of tests/measurements on the calendar. At one point, I was safely measuring at four month intervals and was thinking about stretching them to six.

What does planning like this give me? The pleasure of giving the disease not one more minute of my time than is absolutely necessary. The pleasure of being fearless for long periods despite having an incurable, universally-fatal disease. Yet so many of my friends have turned their disease into a hobby! They devote obsessively large amounts of time to irrelevant considerations, such as following cutting-edge genetic-level research into improving prognosis (which is at the moment either unavailable or useless to us in making nearly all but a very few treatment decisions), studying potential causes of the disease or the mechanisms of the disease,  monitoring disease activity as often as their exasperated doctors will allow, or research into new therapies that will take years before becoming available, if at all. I think that every minute I don't spend obsessing about multiple myeloma is a minute I can spend living a normal life.

When I tell this to my obsessed friends, that I spend as little time as I possibly can thinking about, discussing, or studying myeloma, they tend to look at me with confused stares. I tell them there is no survival advantage to using my time in this way, so why do it? Maybe they disbelieve me, maybe they think I'm just nuts, but mostly they just resume talking about their obsession as if I hadn't said a word. I might as well be exhorting them in Latin for all the good I manage to do. Reason is remarkably ineffective once fear-based obsession has taken hold.

I tell them, decide what that maximum safe measurement interval is in their particular case, set their alarm clocks to that date (that is, the date when they will next have to do their labs), and realize that between now and then, there is no survival advantage to thinking about their disease. They will not die a minute sooner if, between now and then, they deny the disease a second's thought. Instead, they can live as normally as their physical condition will permit. When the alarm goes off, study the labs. Is it time to make a change in treatment? If not, reset the alarm and return to the joys and sorrows of normal life.

I've reached a treatment decision point. My labs are horrible. The evil numbers are sky-rocketing while the good numbers are falling:

And it's not just the numbers: neuropathic pain has increased to the point where I need Vicodin nearly every day; I have developed a minor but annoying case of osteonecrosis of the jaw; and steroids, which drive me crazy, don't seem to be providing any benefit.

The problem is that I've already become resistant to the small handful of standard chemotherapies for multiple myeloma, I'm not a candidate for a second stem-cell transplant even though I have stored the cells for it (because of extensive plasma cell infiltration of the marrow), and Medicare won't pay for a reduced intensity allogeneic transplant from a matched, unrelated donor until January (I'll explain that life-threatening annoyance in a subsequent post). Which means, between now and then, I can't afford to do nothing and there's little that remains to do but swallow the arsenic.

Arsenic trioxide (Trisenox) is given by infusion, not by tablet, and it's just as terrible to endure as you might imagine. Because it works completely differently from the other therapies, it has a reasonable chance of working for me, and perhaps it will work long enough to get me through January and the allogeneic transplant. The trick is to administer enough arsenic to be effective in fighting the cancer without actually killing the patient (viz, me). If you're wondering what the last-chance, last-ditch chemotherapy is, arsenic trioxide is probably it. One person I know went deaf from it (although his hearing eventually returned). As an avid pianist, the thought of losing music is difficult to bear. On the other hand, the neuropathic pain is limiting my practice time as it is.

Because so few have had to take arsenic, I'll be reporting on the experience extensively as it turns me into a hairless baby spider. Meanwhile, it is time to resume the honeymoon (we filed for Ivonne's green card a couple of weeks ago, which is a paperwork and expense ordeal not dissimilar to chemotherapy).