Tuesday, March 31, 2009

Let the Games Begin!

Today I started the first cycle of DVD-R, which consists of infusions of Doxil, Velcade and dexamethasone, followed later in the evening by Revlimid. Nine hours have passed since the infusions began, and in an hour I must swallow the Revlimid, which I hate (I'm not too fond of Velcade, either; Doxil I've avoided until now because it causes permanent heart damage and is otherwise nasty). Already I can assure you that this chemotherapy is every bit as brutal as I feared it would be (see dex's nastiness).

In each twenty-one day cycle, infusions are given twice a week for two weeks. Revlimid, in capsule form, is taken nightly for fourteen days starting on the day of the first infusion. The third week is a holiday to allow for recovery before starting a new cycle. The holiday can be extended if the lab tests show inadequate recovery. Or if, as in my case, the patient whines a lot.

What makes enduring DVD-R so difficult emotionally is that I don't believe it will work well enough to make the second transplant worthwhile, well enough to postpone my having to play in the End Game. I have already failed Revlimid as a single agent, and my response to Velcade (with Cytoxan in a modified version of a regimen known amazingly as CYBOR-D), although good, was inadequate as a pre-transplant chemotherapy. Even dex, our most reliable, effective weapon, has recently shown signs of weakening, which is one of our worst general prognostic indicators.

Despite the lack of supporting science, I nevertheless have hope (not faith) that after the first cycle I will be surprised by a strong, positive response — getting such an unlikely response is, after all, the point of the attempt — making subsequent cycles easier to bear. I'm not by nature a gambler, but I understand that it helps to feel lucky when playing against long odds....

You know you're in the End Game when your best course of action's chance of succeeding is less than fifty-fifty.

Saturday, March 28, 2009

Clinical Trials and the End Game

Clinical trials of new treatments are of the utmost importance. Without them, doctors would still be bleeding us for the ague. A proper clinical trial provides a bit of unshakable truth in the struggle against cancer. Participation in clinical trials is often presented to the newly diagnosed as if it were a routine or natural thing to do. There are even those who will suggest that there is a duty to science or humanity to be part of a process that might lead to cures for presently fatal diseases.

If Christopher Columbus had said, “Oh, I don't think I will try to discover a New World because the voyage will be dangerous and we may not make it,” he never would have had a day named after him!!!!!!!!!
— A fellow myeloma patient
Is having a day named after you worth your untimely death? I strongly recommend that most patients stay the hell away from clinical trials.

I believe that volunteers in the best sense of the word participate in clinical trials as a way of doing good. While I admire the motive, I think they are nuts to do it. Let some other, more desperate person take the pill and the associated risk. It isn't the patient's job to advance the cause of medical research; his job is to fight his own cancer as effectively and courageously as he can.

"No bastard ever won a war by dying for his country. He won it by making the other poor dumb bastard die for his country.”
— Attributed to General George Patton
If someone is in reasonable physical shape, has recently been diagnosed or is responding to routine first-line therapies, and, therefore, the disease is not progressing out of control, then one doesn't actually need to participate in clinical trials and, therefore, shouldn’t.

You may have read of a relatively-recent clinical trial of a genetic-level cure that in a matter of minutes destroyed the livers of the participants, a problem that did not show up in animal testing. I personally had a friend who, although an excellent candidate for a conventional transplant (listen to me call the most punishing procedure in all of medicine “conventional”), saw the seductive promise of cure in a trial of Holmium-16.

The idea was that a small dose of Holmium, a naturally-radioactive substance, would home in on the marrow, help Melphalan kill the old marrow by radiation, and then be flushed from the body in less than an hour, making it harmless. If transplants failed because of incomplete marrow ablation, with Holmium there was the promise of cure. Cure, so achingly seductive, so necessary!

She died a few months later. Actually, her bones died first from the “small” dose radiation. As someone who has studied delayed radiation in Hiroshima and Nagasaki, I should have remembered that there is no established dose of such substances low enough to be considered safe. I too was blinded by the promise of cure. I encouraged her. I feel guilty about doing so to this day; she might otherwise still be alive. I am.

Yet there is a time to consider participation in clinical trials. For me it came with the End Game milestone. Participation makes sense when you are clinically desperate. If a patient has relapsed after responding to one of our usually-reliable therapies or become refractory (failed on more than one) or is demonstrably belongs to a very high risk category—and the remaining choices are unlikely to stabilize the disease for any meaningful length of time—then looking for a promising clinical trial is better than looking for a hospice.

The downside of this high-level of prudence is that many early clinical trials only accept volunteers who are recently diagnosed and/or previously untreated. Therefore many that seem promising will not be open. However, new treatments seldom come from these early clinical trials. There are always more advanced trials, where the risks and benefits are better known, and others designated for the relapsed/refractory category (or are open to all). Here is a link to the national data base of clinical trials.

In my opinion, fear (or its more handsome twin, hope) is the biggest risk to us, whether we are among the newly diagnosed or the veterans. With a handful of exceptions, multiple myeloma is incurable and universally fatal. This fact cannot be wished away. Fear of death can drive us toward any promise of escape, however foolish: inadvisable gambles seem attractive; denial stops decision making because there is no need for it; fortunes are spent on "alternative" treatments; the good in present life is degraded by obsessing on the future bad. This blog is indirectly devoted to providing tools to help neutralize anxiety, regardless of the kind of cancer you may be fighting, so it never drives or degrades treatment decisions. All of my big medical mistakes have stemmed from yielding, consciously or unconsciously, to fear.

Sunday, March 22, 2009

The End Game

I reached a significant milestone in November. I am now officially at the beginning of the so-called End Game. The term comes from chess, where every match is somewhat loosely divided into three phases: a formal opening game where initial sequences of moves (called "openings") have well-recognized names and can be found in books; a development section, where the objective is to gain every possible advantage (positionally, strength, and number); and the end game, where the King is won or lost.

My plan was has been for a decade to have a second autologous stem-cell transplant (aSCT) at time of progression after my first transplant (which was in September of 2005). The second aSCT would buy me some additional good time. I have cells harvested in 1998 just waiting for it.

In February, after six or seven months of Velcade, I was good to go. Except that the bone marrow biopsy revealed between sixty and seventy percent plasma cell infiltration of the marrow (normal is two percent).

At that moment I entered the End Game. The cancer, although not damaging to me at the moment, is progressing, resistant to some degree to every chemotherapy we've tried (e.g., Velcade, Revlimid, Cytoxan, Thalidomide), and, by some tests, is showing a higher-than-comfortable level of activity.

Not my arm, just an example
I know I'm not being physically damaged at the moment because a recent CT-Pet scan revealed evidence of healing in all the spots where the cancer was previously active except one on the seventh thoracic vertebra, and the activity there was no higher than it was on a previous scan in 2007. For those of you who are unfamiliar with multiple myeloma, the cancer eats marrow-laden bone from the inside out (e.g., pelvis, skull, spine, ribs) as it destroys the ability to resist disease.

The difference between the End Game and what comes before it is that the unpredictability of the future is greatly reduced. The cancer will progress at some point on the minimal treatment I'm now giving it (high-dose steroids on two consecutive days each week), and when it does progress it will be difficult or impossible to stop. Imagine a Champagne bottle with a part-way extracted cork and a snarling demon shaking the bottle! That's what I'm seeing today.

If I go ahead with the aSCT with my present level of plasma cell infiltration, there's a good probability that I wont benefit enough from it to balance out the agony of the procedure itself and the lengthy convalescence from it. Looked at from a quality-of-life (QOL) remaining point-of-view, my QOL might actually be reduced when comparison to what it might have been had I skipped the second aSCT, and my remaining life from today (they call that OS, or "overall survivability") might actually be the same or shorter. So instead of enjoying months of relatively good time before the final fight begins in earnest (when you'll start seeing the words "end-stage" or "terminal" on this blog), I would have suffered more than was necessary or beneficial.

When the cork does fly out of the bottle, I'll have little or nothing to hold it back. I don't think anyone can make reliable predictions, but if I had to guess, I'd say that the cancer will blast past the steroids I'm presently taking by the end of summer and that I'll survive about six months after that.

So we're going to try again for the second aSCT. That means, essentially, throwing the kitchen sink at the cancer in a last-ditch attempt to get the plasma cell infiltration down to an acceptable level (less than ten percent). The chemo will be brutal, probably involving a combination of Velcade, Revlimid, Doxil, and Dexamethasone, but if successful any damage or pain caused will be reversible and I'll gladly forget all about it.

Having a successful second aSCT will pull me back from the End Game for some length of time, probably for at least two more years. During that time I might be able to live a relatively normal, mostly drug-free life.

There would also be a reason to hope. There are no new drugs I am aware of that will become generally available in the next year or two, so without the aSCT, when the cork flies out I'll have nothing with which to fight but the drugs that have already failed. On the other hand, in two or more years there may be new treatments that could keep me going, or even enable me to have a third aSCT.

Friday, March 13, 2009

My Bucket List

My Bucket List
I never saw the movie, but I understand a bucket list to be a list of things to do before one dies (that is, “kicks the bucket”). I’m in fairly good physical shape at the moment, when you consider that I’ve been fighting an incurable cancer for more than a decade. Although I’m not in immediate danger, off in the distance, barely visible through the haze, I can see it coming.

When I was diagnosed in 1998, my prognosis—How long have I got, Doc?—was about three years with conventional chemotherapy, five with a stem-cell transplant. Thus far I have lived more than twice as long as that, which I believe to be the result of a combination of out-of-the-box thinking and plain good luck.

Now, though, with my cancer having become difficult to treat, a second transplant nearby but dangling maddeningly out of reach, and seeing no clear path ahead, I’ve started working on my bucket list.

There’s not a lot on it, but reconciliation with my children certainly comes first. I have a son and a daughter, now forty and thirty-six, whom I have not seen in decades; much of the time, I didn’t even know where they were. There has never been any attempt to contact me. My every attempt to contact them has up to now been met with silence or worse.

According to your responses to my posts thus far, I may have led you to believe me to be rational in the face of adversity. Now I have to write about a subject that is harder for me to think clearly about than even the cancer. Because of the history and sensitivity, some irrationality will undoubtedly slip through. I apologize.

I have no good explanation for why I married back in 1968 except that for the first time I was entirely on my own; graduating from “mother Yale” to the chaos of UC Berkeley was a scale-nine seismic shock. I imagined that if I had died suddenly under Sather Gate...

...I would have been stepped over or around until the stench forced the groundsmen to toss me in a dumpster. I think I married because I didn’t have the maturity to handle the world’s indifference.

It’s not just that we were merely temperamentally ill suited, or that she came from a traditional Southern family (boy, was I ever a damned Yankee), or even that we shared the maturity and personal qualities of a yearling alligator. There was something deeper; many of her more emphatic feelings I simply could not understand and still can’t.

I have to say that what I am going to tell you now is just my opinion. I make no claim to authority here, especially when edging close to describing behavior or character that another might consider pathological. Recent events have been difficult, but I bear malice toward no one. (My legal team has made these facts unmistakably clear to me.)

I felt a kind of irrational darkness in my wife that I could not understand; the inner fires seemed a touch hotter and less explicable than those of simple neurosis. Now, neurosis is a subject I know first hand, having withstood sixteen years of analysis. (Yes, I'm bragging: who among you can lay claim to have been psychoanalyzed!) Eventually, I developed a self-observing ego that could sense inappropriate emotion stemming from the the confusion of present circumstances with childhood trauma. What I saw in my wife was not what I recognized as neurosis.

I am reminded of the poetry of William Blake in his old age, if you’ve ever tried to get your mind around it! The problem is empathizing with the emotion or affect in the poems. Can you put yourself in the shoes of the poet? See how well you can manage. If you get a sense of what he's writing about, you might consider getting an English degree. Academia needs you.

I’m not going to rehearse the eerier events in our relationship, just to mention that it was somewhere between difficult and impossible to carve out a safe place for the children. I’ve forgotten what the Final Order of Visitation actually cost me (I would publish it here were it not in paper form), but, in the end, it was some sixty-five pages in length, covering absolutely every eventuality; for all I know it may well be the longest and most complex visitation order in the history of California divorce courts. As a result, for a while, I was able to get my kids out of the middle, at least with respect to visitation.

During the whole of their minority, I never missed a single visit except when on business travel. I was seldom or never late in fetching them. Also, and for the same reason, I paid every cent of my alimony and child support—I didn’t want my children to wonder for one second whether something else in my life was more important to me than they were. There wasn’t.

On the other hand, I felt as if all of the special powers of motherhood were making it as difficult as possible for them to have a normal relationship with me. I tried to be scrupulous at all times; I acknowledge that there were times when my halo slipped. In any case, the need to be scrupulous was not reciprocated. It was all-out war.

Here’s how it worked out. Because I had the court order in place, my children could always say to their mother, or even to themselves, “I’m going to visit my father, not because I love him, but because the court order says I have to.” The day they turned eighteen they could no longer hide behind the order. They would have had to reply, “I want to.” That was an option they were not allowed.

As a result, I never saw them again. I feared that they were broken like horses to the saddle.

Still, I remember when it was obvious that they loved me very much.

My beautiful son and I had the kind of special father-and-son relationship every dad hopes for, at least until he neared eighteen. I love remembering the tobacco-chewing contest (we chewed to a draw, which surprised me), teaching him to ride a bike, eating a poison plant on a dare from his step-brother, and any number of private jokes (Cujo—eats big, ....). He was a contented lad, popular with his friends, thoughtful and funny. First in his class in a huge high school.

I was more worried about my daughter. From an early age she seemed to lack empathy and the compassion that stems from it. My second wife and I talked about this often in quiet tones. Perhaps chemo has rotted my brain, but I cannot to this day remember a single instance in which my daughter tried to comfort someone else (I have many fond memories of compassionate behavior in my son). On the rare occasion of tears, I thought I saw a bit of crocodile in them. There was much of the macabre in her tastes. I'm not sure it was an act.

The reasons for making contact with them after all these years are of course complicated, but, at bottom, I did not want to die without giving them the opportunity to make peace. Once I'm gone, they will be stuck for life with two things: their childish understanding of the relationship between me and their mother; moreover, they chose not to make peace when they had the chance. Both would hurt them permanently.

For my benefit, I wanted to know this: did my children thrive despite the pressure that was put on them? Were they mentally healthy, had they formed normal personal and intimate relationships, were they well adjusted, independent, progressing in their careers and pursuing reasonable goals by reasonable means? In short, were they happy? Or did the pressure they were put under during the marriage and divorce scar them indelibly?

I certainly hoped they were doing well, although their long silence argued otherwise. Two weeks ago, returning from a devastating meeting with my hematologist, I decided to just simply drop in on my daughter at work; all this time she’s lived right here in town. I’m not going to go into detail about that meeting, except that, on the surface, it went reasonably well. Later she told me that she had “freaked out” afterwords, so much so that the company visiting rules were changed. I hope she didn’t raise eyebrows enough to hurt her standing with the company or to damage the woman who escorted me. Nothing overtly happened that should have raised alarms. For her own sake, she should have finessed her distress and simply gone home.

Nevertheless, in the last few moments, I sensed some some hope for reconciliation. I imagined I saw an aura. Yet after two weeks of unanswered emails, with me growing increasing alarmed that my ice-breaking visit had not resulted in broken ice, but also might be providing her a degree of passive-aggressive pleasure, I tried again.

This week, Sunday, I rang my daughter’s doorbell, hoping, at least, for civility. Unfortunately for all of us, what I found seemed neither civil nor normal.

How was the desperate and desperately ill father greeted when the door opened? The first word out of her mouth was “Noooo!” Then, emphatically, percussively, conclusively, and in a guttural, almost feral tone: “No." Pause. "NO!”

I sensed neither empathy, nor compassion, nor even respect—just a dark, intense rage. She began to recite a litany of my recent sins, during which it became apparent that nothing I have said or done has been inoffensive to her. If I emailed her some of the kind words others have said about me, I was being “self-aggrandizing.” (Had I sent her criticism, it wouldn’t have been critical enough.) She was angry that I had found her, and angry that I had not found her earlier. She had forgotten that after an "Oh boy," she hung up on me during an early attempt at conversation. There is much she has repressed.

I asked what I had done that was so unforgivable. She replied, digging back two decades or more, “You said bad things about my mother.” That was it. I wasn’t seeing her rage, but her mother’s rage, by proxy. Some psychologists might call this “identification with the aggressor.” If this is what I was seeing, and this is only my opinion, the identification seems to be complete. My darling daughter is gone. I have been disconsolate ever since.

However, I was wonderfully surprised and delighted to meet her long-term companion, who I found to be decent, friendly, and principled; he showed solid character three times while we talked. The moment he saw me he rushed out of the house to shake my hand. When that didn’t seem enough for him, he gave me a hearty hug. He said this meeting had been too long in coming. When my daughter left the door to finish dressing (she had refused to ask me inside), I realized that he had been told absolutely nothing about recent events, even to the point of being completely unaware of my battle with cancer. He was sincerely shocked to learn of my condition and tried to give me hope for survival. I told him that meeting him was on my bucket list, and that I was delighted to be able to check that item off the list.

I did like him a lot. I told her when she returned that I could see why she liked him. He suggested meeting over beer. We agreed on a bar called Callahan's the Wednesday following.

"The Earth is firmly fixed; it shall not be moved."
-Psalms 104:5

This bible verse shackled the minds of men for thousands of years, and held back the advance of science. It was this verse that was used as evidence against Galileo, who argued for the theory of Copernicus, that the earth is not immovable, but rotates around the sun. It was for teaching this that he was called to Rome in 1633, and tried for the crime of heresy. The aged Galileo, in his 70's, was taken down into the dungeons of the church and shown the instruments of torture that were going to be used on him if he did not recant. Fearing the torture, and fearing that he might share the fate of Giordano Bruno, whom the church burned at the stake a generation earlier for the same crime, Galileo recanted the truth. He was confined to his home under house arrest, neither allowed to leave or to receive visitors, for the last seven years of his life.
Afterward, I fear my daughter had shown him, like Galileo, the instruments of torture. Or maybe her mother had brandished her extensive collection to everyone in the tribe. In any case, the beer was called off. And that was it. Instead I got a pedestrian text message listing each of the individual ways I was to avoid future contact. I’d wager the entire sorry tribe participated in its production. I give the companion little credit in its writing; I still think he's a right guy. I wanted to learn about him, his parents and his childhood and the like, and I am disappointed. Here is part of the text message I received on Tuesday, slightly altered:
1. Your daughter would prefer you not to come by the house anymore.
2. She also requested that you not come by work either.
3. Your son has also asked that you not contact him or his wife
4. Please do not ask emissaries to intervene on your behalf with any of us
5. Do not employ semaphores, mirrors, or other devices in an attempt to call attention to yourself
6. Please do not ask anyone to inform us when you have died
7. Please do not contact me any further.
Ok, so I made up three of the responses, but you must admit, the others are rather strange. Of what are they so deathly afraid? Why can't my son tell me what is on his mind face-to-face like a grown man? In what possible universe do I constitute a risk? Did neither of my children inherit my courage or decency?

Perhaps it is harder to be courageous or tow your own line when at age thirty-six you live in a house you rent from your mother (who, by the way, lives about a mile away). But I'm just guessing here.

When first diagnosed, I stumbled across words that were enormously difficult to accept: that multiple myeloma is an “incurable, universally-fatal cancer.” Yet, in accepting these unthinkable words, I was given the gift of clarity. Those who hide from or try to deny such hard truths find it more difficult to enjoy the good time that remains. Denial takes a lot of energy. Like a cancer, it spreads to cover all manner of other thoughts that might lead to the big, unacceptable conclusion. Quality of life is diminished. Moreover, the work of accepting and being prepared for the likely future isn’t done.

Which by their denial, ironically, is the fate to which my son and daughter have consigned themselves.

So I accept that my daughter does not love me and admit that I’m not sure she ever did. (My son did love me, of that I am sure.) I also confess to being more disappointed in them both than I ever imagined possible. Thus far, I have seen nothing to admire in either one. That may be harsh, but it's true.

Wonderfully, after a few difficult, lost days, this morning I can write again, which is my path to understanding. The guilt I felt toward my minor part in breaking my daughter is gone. In a surprising and unintended way, I received the absolution I needed from her, albeit in a terrible form. Although she is lost to me and perhaps to herself, today I can absorb her coldness and that of the world, which I could not handle in 1968, and move on. Cancer is a great and terrible teacher. Or as my Chairman of Computer Science once told me, he who matures last, matures most.

It is time to move on to the next item on the list. Perhaps it is my son, although persuading him to come out of hiding might require an extraordinary legal action.


Blogger Sandy said...
Lonnie – It is extraordinarily difficult to reconcile with individuals who have been brainwashed to believe something about you as “the truth” when in fact it is not. But what you said about your daughter not having any demonstrable signs of compassion may be an indicator of a deeper inability to connect, especially given the maternal genes. We want, when we marry and have children, to have the hope that somehow everything will work out right and we will leave a legacy of both genetic and philosophical value for the rest of the world to enjoy, benefit from, who will re-create and tell our story. I have on my blog a song by Martina McBride called “Anyway.” She reminds us that people walk away, love is not returned, songs are not heard, but to “do it anyway” – love, sing… whatever.
We cannot know the future, but we can offer our love and our songs and our selves to those who care to meet us – and some will remember. Imagine having a friendship with someone who has a brain that is shrinking and every day that individual remembers you less and less, can’t recall how you met, cannot bring up the memories of days on the beach, funny experiences, etc. and as you meet up or talk on the phone, each conversation is less and less rich historically, but at the same time that exchange is just as lovingly done as ever… quite weird, but a reminder that love is not something that is necessarily acquired by genetic connection, intelligence or even memory.
There are still children and grown-ups who can be touched by you, Lonnie, and who will remember who you are forever. It’s not my business how you invest your time filling the bucket, but I hope my thoughtfully crafted words will offer some hope for the time ahead. I came to your blog seeking answers, information and personally for comfort as I have a loved one with MM, who has had two auto’s which aren’t progressing as hoped, and perhaps will have an allo very soon. This is a hard adversary to overcome and the emotional challenges are no less. What you have offered up to those of us who come here is an authentic individual – no holds barred, it appears – and whatever comfort I can return to you, is my paltry gift, with blessings.
March 14, 2009 11:40 AM  
Blogger Lon Nesseler said...
I wonder whether or not making and working on the items in a bucket list isn't a strong sign of acceptance of the unacceptable. Recently I crossed an important milestone: clinical trials are now relevant for me (I never recommend them if there are better options).

Meanwhile, the subtext of the post, is that once you've started working on your bucket list, the items are not necessarily going to be fun and/or easy. I can't imagine trivial things on it. Maybe I should see the movie, because the trailers seem to indicate that the pair are doing things they've always wanted to do, not the things they've always put off because they didn't want to do them.
March 14, 2009 2:08 PM  
OpenID goodbloodbadblood said...
Hi Lon;

I don't know what to say. The honesty blows me away. It's a rare gift when a stranger invites you into their life's essence. Thank you.
March 15, 2009 7:14 AM  
Blogger tim's wife said...
My sister always says when referring to divorce, "you've gotta love your kids more than you hate your ex-spouse." Obviously, your
ex-wife was not capable of that kind of selflessness and maturity. She chose instead to deny her children an important relationship and the damage it caused them is evident. It's
very sad that even at the ages they are, they cannot recognize her role in their unhappiness.
Sandy's right. It's brainwashing and unfortunately, it's what they know and are
reconciled with. There are many things we should not pass on to our kids.
Our fears and grudges first and foremost.
You tried and that's all ya can do in a situation like this.
March 17, 2009 6:07 AM  
Anonymous Anonymous said...
I don't know you, but I can see that you're in a great deal of emotional pain. I have been helped by going through processes created by The Journey (www.thejourney.com). Maybe such a process will bring you inner peace. MM loves stress, so the less, the better. A Journey practitioner should be able to help you, or you can go through the process by purchasing a CD on the web site. Call the Journey's phone number to inquire about both, if this interests you. (973.680.0271)

March 22, 2009 11:56 AM  
Anonymous Anonymous said...
Im so disappointed with your children's response to you. They have clearly been brainwashed by your ex. But I feel you showed such courage in reaching out to them despite the risks of rejection. It appears your daughter is long gone. Your son may come around. But if not...you dont ever have to wonder about the "what ifs". You reached out to them...you tried and now you know. It might be healthier for you to relase them both (as best you can emotionally) and focus on your fight. You are highly intelligent Lon... plot your next move, keep thinking outside of the box and out smart this thing once and for all.
Tammy M.
April 22, 2009 5:42 PM  

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Tuesday, March 3, 2009

You can't know where you're going until you know where you are

On 4 November 1922, Howard Carter found the steps leading to Tutankhamun's tomb, by far the best preserved and most intact pharaonic tomb ever found in the Valley of the Kings. On 26 November 1922, Carter made the famous "tiny breach in the top left hand corner" of the doorway, and was able to peer in by the light of a candle and see that many of the gold and ebony treasures were still in place. He did not yet know at that point whether it was "a tomb or merely a cache", but he did see a promising sealed doorway between two sentinel statues. When asked if he saw anything, Carter replied: "Yes, I see wonderful things".
—Wikipedia, edited

Like Carter, squinting in awe through a small hole, genetics for the first time can glimpse the machinery of life at work. As stunning as Tutankhamun's treasures proved to be, they are as nothing when compared to the marvels beyond this new doorway. Carter saw a tomb; genetics sees life itself.

Although our perspective is limited and the machine is vast, the biggest and most complex in the universe, a few of the smaller and nearer components are becoming known. Experimenters are inserting probes through the hole in attempts to determine cause and effect. Some are even trying to repair what may be the diseased (that is, broken) parts of the machine.

The idea of genetic engineering is rightfully frightening (see Lebensborn), yet we stand on the threshold of a new era of medicine in which many incurable diseases will become curable. Birth defects will be corrected. Deformity and damage repaired. The mind gasps.

What is painful today is that some broken parts have been identified but very few can be repaired.

To bring all of this crashing down to earth, the pathology report from the bone marrow biopsy that stopped my life-lengthening transplant last Friday shows that my marrow genes are not expressing cytokine CD45. This paper, which I found yesterday, and which is not an easy read, says that if I go ahead with the transplant, I may get a good initial result but it won’t last long and the cancer is and will be resistant to other chemotherapy.

When I was diagnosed, I had little understanding of the calamity that had befallen me. Medicine was something I never had an interest in studying, but suddenly I needed to understand, not only what was happening, but also what would happen to me. What I learned made me realize that when you have an incurable, universally-fatal disease, such as multiple myeloma, you have a responsibility to participate in the treatment decisions that are made, since they’re all bad.

The result, after arduous study, was a long-term plan for how to manage my cancer. For example, although my stem cells were harvested in 1998, I decided to delay the transplant itself until 2005, reasoning that since the evidence showed rather a fixed benefit for the first transplant, the longer I could easily delay it the longer I would survive. I thought I would also benefit from using the 1998 cells, wrongly as it turns out, because they were not far evolved and had not become resistant to chemotherapy.

Part of the thinking was correct. I’m still here, nearly eleven years later. When I was diagnosed, the average survivability with transplant was five years.

My point is that I had made a plan and was able to follow it. A plan lets you see into the future, which is a comfort in itself, but a good plan may give you some control over your destiny, which for me was an even greater comfort. It is not all illusion, not always.

Then came yesterday’s CD45 report. For the first time in a decade I found myself demoralized. The plan I had been following is gone. The threshold I’m standing on leads to terra incognita, which to my ear sounds a bit like “terrified.”

One of my dear friends advises that now is the time to be existential, and I can’t argue with that. It is important not to give the cancer one extra minute of thought, but rather to embrace all of the wonder and joy of life that is everywhere. Since diagnosis, I have come to live much more in the present, much more as a part of the moment. I love the feel of sunshine on my skin.

Yet I strongly believe that it is necessary to ground oneself in the truth no matter how painful or unwelcome it might be. The truth is what puts solid ground under the feet, providing a valid basis for hope and direction. Now is not the time to look away and lose my way in religion, resignation, rage, fear, dietary supplements, or a last trip around the world.

Yesterday was difficult, having to confront these demons, but I survived. So instead of feeling as if I am at the end, I’m glimpsing a way ahead, albeit, like Carter, through a tiny hole. Already the wheels in my head are turning and plans are forming. I’ve found a couple of clinical trials that have promise.

But that can wait. This morning may have had a bleak look to it, but San Diego has rebounded too, bright with the kind of winter sunshine that makes it seem wonderful to live in such a boring city. It’s time to go outside and enjoy it.

Sunday, March 1, 2009

Relapse, Error, and Fear

I wrote this email to my doctors early last year when I dropped out of remission after my autologous stem-cell transplant of 2005. It is a rare admission of error on my part, with an explanation of how to avoid it in the future. It is not an easy read in that I employ some technical jargon and don't explain everything to the unfamiliar, but if you get to the end, you may appreciate the conclusion and might be able to apply it to your own life in some context.

I don't like how I'm feeling. I suspect that the light chain deposition rate is now heavy enough to involve the central nervous system, as it did long ago. For years before I was diagnosed, I had one or more pneumonia-like episodes each year that weren't pneumonia, I sweated copiously all the time, and it was impossible to make a room too cold for me. After treatment, all signs went away, including also high blood pressure, elevated resting pulse, and late-onset psoriasis. Now, some are coming back.

Urgently, we have to get the numbers down for transplant. Not that we wouldn't win an argument with Medicare, since the risk of a recently-contaminated stem-cell harvest wouldn't be at issue, but, still, it is a good idea—which until recently lacked an evidentiary basis, at least to my way of thinking—to lower the numbers as much as possible before transplant. It certainly can't be a bad idea.

So instead of doing 20mg dex weekly, I think I ought to be doing 20mg/day for two consecutive days per week. While being more likely to bring the numbers down quickly, it also is the heaviest dose my tortured mind can stand. Now is not the right time to be looking for the lowest effective dose on the longest interval, which would otherwise be my considerable preference.

Fear is afoot. I am always more comfortable coming to conclusions when I'm staring at evidence, which, in this case, may be found in lab tests yet another week off. Normally, I would resist any premature change in treatment protocol, any change without some objective evidence behind it, and I would strongly resist if I thought that the pressure behind changing was solely the fear of not changing. But I want the aSCT to be started and over with in August, and, clearly, two days of dex instead of one can't make the outcome of the upcoming aSCT worse, despite the enormous stress it will put on me now.

I've decided to allow fear get the better of me in this instance, something I rarely do, which is not bragging; I'm not sure suppression (or repression) of fear is always a virtue. For one thing, suppressing fear in order to think clearly requires enormous focus and energy, which, if high and enduring, can destroy the good aspects of life that remain.

This time, I deserve the fear. The theory behind using the 1998 cells in 2005 was that, when the disease came back, it would very much resemble what it was in 1998 (responsive, because nearly naive to chemotherapy, and unevolved). The theory turned out not to be true, although I believed it.

Which means that incomplete marrow ablation is the dominant factor. A decade ago, when I first tried to find out why transplant failed, I asked about this with every expert I ran into. The answer usually was, we can't get an uncontaminated harvest; at least one malignant plasma cell gets through, divides, and causes the eventual relapse. A smaller number of others believed that malignant cells survived the high-dose Melphalan. I believed the former perhaps because I liked it better; a contaminated harvest produces a more-desirable outcome at relapse. The returning disease, in theory, would be slower growing and easier to treat if it resulted from a contaminated harvest rather than from incomplete marrow ablation.

In my case, a contaminated harvest could not have caused the appearance of the more aggressive disease I now have because it was frozen (and contaminated) in 1998. So unless cells evolve while frozen at near absolute zero, incomplete ablation is proved, at least in my case, and, by extension, for all. Even if both theories are true, the combined result should manifest first from cells that survive the ablation, that is, those more aggressive (more quickly dividing) and less responsive to chemotherapy.

The reason I'm struggling with anxiety is because I truly did not expect to find myself, at relapse, looking at so few tolerable options. The returned disease was not expected to be more aggressive than the disease in 1998, and certainly not less responsive to chemotherapy.

And yet it is both.

The reason we fear the unknown is that it catches us by surprise and, therefore, unprepared; we do not know or recognize our deadly adversary. With the surprise comes deep and sudden fright, overcoming what before we refused to accept—that closer than we had thought, but still a ways off, lies the grave. I can see it hazily in the distance.

Tonight I am exhausted from fighting fear and think that for a time I will relax and let it have its way with me. In a situation like this, a temporary surrender is needed from time to time to keep ones balance.


PS: No book can be written while in the grip of strong emotions, but only in remembering them. Which is why, since relapse, I haven't touched mine. That may be changing. Like Hamlet, now that the die is cast (i.e., the transplant decision has been made), I may no longer be hamstrung.