Thursday, December 24, 2009

Miracle Two

A year of data
Multi-Drug Resistance. MDR pokes you in the eye from this and older charts. I've tried every drug that's doesn't require being in a clinical trial to get, and failed to obtain at least one that is. In the beginning, when my luck ran high, everything worked quickly and easily. Now, everything works for a short time, then fails. There is very little left I can try. Arsenic. You know you're at the last ditch when your doctor, with a brave, straight face, suggests you try Arsenic. I mean, my ex-wives may have been suggesting it for years, but he means it. (Maybe they, and my unforgiving children, do too.)
My routine numbers look ok (CBC, etc.). There are no known lytic lesions or extramedullary plasmacytomas. I have no secondary diseases worthy of a name. Creatinine low.
On the other hand, just fifteen months ago I spent two full days mucking out my pond with pickaxe, shovel, wheel-barrow and beer. Today, with the neuropathy and bone pain, I carefully plan and minimize trips downstairs. I can't practice the piano for long because of the back pain. The back pain is just strong enough to distract me. I can't ignore it. So I can't play.
And much as I hate it, the skyrocketing Freelite number, as shown in red, just can't be ignored. It's either treat the lab test or die. At the rate of climb, as I said in the previous post:

After more than five months of unrelenting bad news, including the failure of bendamustine after the wedding, the numbers were spiking upward at a rate that meant I needed a miracle were I to make it much longer. Look at the red line, which is a measure of the number of plasma cells (and, therefore, malignant plasma cells) in the body. It doesn't take much imagination to see that if the trend continued upward at such a high velocity, there would be nothing to me but malignant plasma cells before too long. I would have no working immune system. My marrow would fail. And that would be that.

All that was left was to try Arsenic. It isn't likely to bring long-term relief. It may buy a few months at best.

So I found myself doing what one really needs to do when time is obviously short (and, on top of that, having just married and, in the process, acquired four step children). Wills. Titles to houses. Family heirlooms. Finances in general. Pets. Grave sites (El Camino Memorial Park).
But also seeing old friends, mending fractured relationships, "last look" nostalgia indulgence (I'm watching the entire Homicide: Life on the Street series on DVD), working towards a peaceful end. Working my Bucket List, if you will. Striving toward acceptance and peace.

Before we started the Arsenic on November 18th, 2009, I thought an experiment was in order. I had been convinced, from the failure of DVD-R and other regimens with dexamethasone earlier in the year, that I had become resistant to steroids. High dose steroids ruin my quality of my life, so why take Dex if it doesn't help? It took a few days to convince my doctor to let me run a definitive test (or tests). That would be a week of high-dose Dex, which I hadn't taken in many months, a measurement on Monday, and then start Arsenic (first infusion) on Tuesday. If the result of the test showed no effect on the cancer, a result I fully expected to see, I'd skip Dex and take my chances. (Or perhaps keep the dex long enough to see if the combination is what is working, then drop the Dex to see if the success had anything to do with the Dex. And so on.)
Quality of life does matter, even (or especially) when life appears to be short. One way or another, I planned to get off the Dex, if I could, if only to die with a clear head. The doctor initially wanted to throw everything we had at the cancer. If we did, and something worked, we wouldn't know what it was. I could see no added risk in following my more incremental path.
[An aside. Quality of life (QOL) is always a factor but, to tell if someone is truly being rational about their cancer, study how QOL is factored into treatment decisions. In the end, I see too many people disregard the QOL of life issue in favor of the possibility of an extension of life, no matter how unlikely or dangerous. They submit to difficult, low-probability chemos that, probably, shorten their lives. Hope, as I see it, has overwhelmed reason. And I've seen others pack up and quit at an early stage when many chemotherapies might work because fear has overwhelmed reason; when offered Arsenic, for example, they go to Hawaii instead. I can tell, from the nature of the discussion, when QOL has become a rational factor, one of many, in the mix. In this blog, as in my life, the most important skill to attain is the balance between hope and evidence (not, as you might have guessed, between hope and fear, although that's important too). Attaining this balance is a requirement to being an helpful participant, at minimum, in treating your cancer. It requires constant, conscious work to attain. The result is likely to be the longest life with the highest quality possible for each of us.]
So test we did, and the wholly-unexpected drop in the cancer was so large as to be a hit upside the head: stunning, impossible, from another planet. A 2/3 drop looks a lot like a bloody miracle. One that definitely needed an explanation. And, after more than five months of horrible news, which downwardly adjusts large portions of the mind, I needed an upward attitude adjustment. This is not news that can be absorbed overnight. I'm still not through processing.

I got the news at the end of a horrible two weeks. Not long before, I passed by my friend Derek S. who was waiting to see our doctor. He was fully expecting to be put back on DVD-R, which he believed had been working for him. Instead, our doctor told him that there was nothing more that could be done for him, that hospice would be called, and that if there were an emergency, they should call him, not 911. For weeks afterwards I wondered when I would hear the same thing. There was some post-traumatic stress disorder for me, even though I hadn't directly witnessed my doctor's administration of the last rites.
You must understand the timing. I was due to start Arsenic on Tuesday afternoon and had an endoscopy/colonoscopy scheduled for the same morning. If you've been prepped and scoped, you know it isn't fun. I also knew that it would be the day that would be forced to take responsibility for ending the life of my beloved cat companion of nearly eighteen years, Yeti. I could not let my suffering prolong his. November also marked the tenth anniversary of the death of my Mother, and oh g-d did I need her now.
I was also trying to recover from ten days of radiation to my thoracic spine. There was only one active, persistent spot on the CD-Pet scan (the rest had burned out), so it was radiated to preserve future spinal function (I was entering the "preserve functioning" phase of the end game). The radiation had torn up my esophagus, so every swallow was a torment.
The neuropathy in my feet, and undifferentiated back pain, was forcing me into more vicodin than I  would like, up to two every four hours. There was also a pain in my left side after the colonoscopy.
I had wheezing bronchitis that gave me no rest for many weeks. I sounded, upon soft exhalation, like I had swallowed a oboe reed. My bird, Zombie, was starting to bite herself.

And, finally, I had blundered badly in an encounter with La Migra (I have no idea where they truly fit into the complicated immigration structure of today), but they are the police, and I came close to losing Ivonne forever to deportation because of my preternatural naïveté. I was only saved by dumb luck. Which will be the subject of a later post.
At best, I could perhaps expect the Arsenic Trioxide to extend my life a few months.
All I could do was watch TV.
Then, there came the astonishingly good and wholly unexpected response. Why such a response now?
We stopped the Arsenic after one or two infusions and repeated the Dex test. Except I was weak in the knees. I didn't precisely repeat the dex regimen, which was 40mg on Tuesday, then 20mg on Saturday and 20mg on Sunday, followed by measurement on Monday. I got weak. I skipped Sunday. And the cancer number went up a little. Stupid, stupid, stupid. Dex attacks judgment. So after a struggle to think clearly, I realized I had to repeat the first test precisely, then go higher if needed. So the third week I did and the number dropped again. 
From this we deduced, doctors and I, that there wasn't a simple dose/response mechanism here. In a simple dose/response, the more you give, the larger the response, the less you give, the less the response. Predictable. But we were seeing that there is in fact some combination (regimen) of days and doses that was high enough to work, and, if given less than that, in some sense, too low to work. A nightmare for Operations Research to figure out. We had found a trigger or threshold effect. Eleven years in, I'm still learning new things about Dex.
An alternative theory was floated: that there had accumulated a large pool of dex-sensitive cells that were killed off en masse by the the first dose. The rest were presumed to be resistant. After the second week, the Week of the Weak Knees, the question wasn't answered. But after I repeated the first regimen, and got another drop, we could discard the large pool theory. We were definitely looking at a threshold or trigger, as yet undefined, but one that we knew, because of the failure of the second week, we had exceeded but perhaps not by very much. One single 20mg dose on Sunday (missing) made the difference. Adding it back resumed the drop.
And what a difference it made! I had inadvertently opened a door to a way out of the End Game. I mean, this is not just a lab-test miracle, but something that can completely change my future for the better. It in fact has given me a future.
Immediately, we started talking about having a reduced-intensity allogeneic transplant from a matched but unrelated donor. We had a way of lowering the tumor burden that was an essential component of the process.
In an transplant like this, donor cells are given. They are a close enough match to my own, in theory, that the resulting immune system does not attack and kill me, but not so close it doesn't recognize the malignant plasma cells as being malignant. When the match is correctly tuned, the new system attacks the myeloma with a manageable version of Graft-Versus-Host-Disease (GVHD).
Ten years ago, when this was first suggested to me (aSCT, then allo), the transplant-related mortality rate was something like 40%. The matches were done in the in the old way, where a 7-point HLA match was considered perfect. No one could explain why results for MM were so poor while the results for other cancers were so much better. It was not the kind of gamble a beginner needed to take, and not clear that it was the kind of gamble worth taking at the end of the fight, either. It was like playing Russian Roulette with half the cylinders loaded.
However, today, matching is done at the gene level. The old system has been abandoned for us. The probability of transplant-related mortality is now, I believe, a little lower than 20%, and it doesn't kill you on the spot, either. It might take years of fighting horrible GVHD before it kills you, which is a lot more time than I would otherwise have. And there's an additional promise: there's about the same chance of actually being cured (or, perhaps, being in a permanent complete remission). In between? About the same result one might get from a traditional autologous stem-cell transplant.
(Don't quote me on the numbers;  they aren't backed up with published studies, although if any of my readers can point to some in the comments, I would appreciate having them.)
So, to back up, I go from the expectation of certain death in the near future to the possibility of cure in a single week, and that being the week after a horrible month, perhaps the worst in my life.
I believe in evidence-based medicine. Finally, I had evidence I could build upon rather than just cringe at.
And, now, for a short diversion to the South Pole to meet a couple of  characters, Roger Mear and Robert Swan. I have their book somewhere, A Walk to the Pole, and remember only a small part of it, which I will probably relate incorrectly until I can find the bloody thing and correct this entry. I may be miss-remembering.
They wanted to solo walk, unsupported, to the South Pole, old style, like Robert Falcon Scott (who, with companions in a major expedition marred by major incompetence, died trying it in 1912). But here's the part that I may be ascribing to the wrong fools. They studied the plans of another man who had planned such an expedition, perhaps to take place in the 1920s, that might succeed where Scott had failed. Amazingly, the man was still living, I believe, in Switzerland, and still had the plans for the never-undertaken expedition. He was in his nineties. The lads visited him and spent time studying his plans. These plans, you must understand, were for their time as large and complicated as those which took us to the moon. Warehouses full of paper. It took major planning just to get the expedition to New Zealand, let alone Antarctica.


When Mear and Swan had finished with the study, they came up with a sentence that will forever stick in my mind. They said, quoting from memory, "It was the perfect plan: there was no margin for error." Which, to this day, represents to me the most concise self-contradictory statement I've ever read. The perfect plan would have contingencies for every possible eventuality! The perfect plan would never lead you to a place where there was nothing you could do but die. How nuts can anyone be? (Read the book. Pretty nuts.)
Well, here's my perfect plan.
First, we use dex alone to get the number down as far as it will go. When the number stops dropping under the current regimen (Wed 40mg, Sat 20mg, Sun 20mg), we go up to see if whether above the threshold there is a common dose/response mechanism operating. If so, we ride the number down some more. Then, when we're sure we've gotten out of dex what it can do, regardless of the depth of the result, we add Arsenic. This is because the allo needs a period of three months in which no chemotherapy can be given. Chemo would destroy the graft.
That doesn't mean I have to be in complete remission for three months. I might very well have an increase in the cancer that would normally indicate treatment. But the increase can't be so bad that I have to have it during that period. Arsenic Trioxide is all I left have that offers the promise of such an additional benefit. Dex alone can't be counted on to provide a long quiescent period after cessation.
Because of the response, and the period of Dex alone, when we add back the Arsenic we will be able to see whether it is effective and measure the effectiveness of the Arsenic/Dex, if any. If it helps, we can ride the number down more. The allo would take place when the minimum was reached on the combo of dex and Arsenic. There is no possible way to predict when that moment will come, so the timing depends upon lab tests. A wild guess would put the date for the allo in February.
In the meanwhile, Medicare, which I'm on, does not pay for allo transplants for multiple myeloma. Period. Good luck discovering the reason why, and, when you do, please tell me what it is. On the other hand, there are two Medicare Advantage HMOs in San Diego who claim they will cover the procedure if it can be shown to be medically necessary even if Medicare itself will not. How likely is that? We've tested the system gingerly, and maybe it's true. So on 1 January I switch to the one of them that uses my transplant doctor's organization as a provider (talk about good luck) and we go for medical necessity. Will it be approved?
Then we have to find a compatible donor. It may be easy, it may be impossible. We won't know until we can start looking, which can't happen, I believe, prior to the authorization for the allo.
If we have a donor, and we have our numbers low enough, and the insurance will pay, then it's a go.
After that, it would be good to find myself in the 80% or so that is not killed by transplant-related GVHD.
To sum up, it is the perfect plan: there is no margin for error. Every one of these steps has to be successfully reached, none are certain, but the chances of reaching them aren't stupidly small either.
There is even a realistic chance of cure in the probabilities somewhere.
Now tell me this isn't a miracle!
I've lived without hope for months. I am unable to base hope on religion or delusion. I need something real, something tangible, evidence, if you will, upon which to base hope. I had none. Everyone wants you to have hope. They call it thinking positively, or having a good attitude, and imagine, somehow, that a hopeful person is more apt to survive than one who feels hopeless.
But hope clouds the decision making process. It is what causes people to lumber to clinics in Mexico to be injected with extract of peach pit (Laetril). Or eat massive amounts of macerated fruit. Or imagine that g-d has cured them and that they need no further treatment. Or frantically insist on being over-treated despite all of the evidence in the world that it will make their remaining time worse or shorter.

But real hope, based on data? From that you can derive a plan, something rational that can be done to improve your chances of survival significantly. Doors swing open, the maw of the grave recedes, and the biggest gift of all — time — can be used to advantage. There can be a plan that makes sense, even if it is a perfect plan. You can know what to do and when to do it.
I have hope. I earned it. I can indulge in it. There is a plan. I'm following it. I feel better and stronger every day (as the numbers drop, as my gloom recedes). I can have a future and it is ok to anticipate having it. I might even beat this thing.
Twice in a single year I have been given miracles. Twice, in what I thought was the least-likely possible period of my life, my hard work and dumb luck and I don't know what else have conspired to make the impossible become possible. I am happy. I have a good marriage. It is likely that I'll live much longer than I thought I would. Maybe, just maybe, I'll be cured. Even though it isn't likely, cure is possible! All I need now is a bit of luck....
Is it not true to say, perhaps, that for an unlucky man, I'm the luckiest man you know?

Scrooge Discovers He Has Survived the Night!


  1. Oh, my gosh, Lon. I had no idea you were going through so much, both good and bad. When did you get married and to whom? I'm so happy for you! I know you didn't feel you would ever meet anyone and get married, but look at you!! I'm thrilled that you have a new plan that looks so promising and I'm praying for you that it does and that you can have your transplant and live to a ripe old age!

    I was very interested to hear about an insurance plan that might cover the transplant because if I ever need another one, since syngeneic is considered a branch of allogenic, it's not covered by Medicare either!

    I'm also interested on the deportation tale you mentioned, so do fill this in for me.

    How old are the children you inherited and do they just love you to death? I had my 9 year old grandson living with us for 6 months and could not take him any longer. He is back in Texas, thank the good Lord. This is a child with lots of emotional problems, ADHD and oppositional defiant disorder. He is very smart, too. He just challenged by authority at every turn and had absolutely no respect for me, though he loved/hated me and I him.

    Lorna Newlin
    About to go to the oncologist in two weeks to see if I'm still in remission, which I think I am.

  2. Natalie Krohn, Leiomyosarcoma survivorDecember 25, 2009 at 12:59 PM

    My best friend has recently been diagnosed with Multiple Myeloma. After a trial of Thalidomide, her latest MRI showed progression from L1 into L2 L3 L4 and possibly L5. She goes to Mayo in a few weeks. I myself am a 10 year survivor of LMS (Leiomyosarcoma) - I have helped her as much as I can - but the world of myeloma is so much different. Any help would be greatly appreciated. I am willing to do all I can to help her - her eight children are depending on it! God Bless you for all you do. In the world of rare cancers, it is a blessing to have people like you as resources of inspiration and knowledge. It's a difficult road we travel...
    Natalie Krohn

  3. Wow! What a post. Hope that all goes as
    "planned" and please keep us posted on the
    medicare/insurance deal as it affects many
    mm'ers. I have never heard that you can't have
    chemo for 3 months prior to an allo. I know several who had them and I think they had chemo
    within that time frame. Hmm.

  4. Tim's wife:

    No chemo after the infusion of donor cells for three months. All the chemo in the world before that :)

  5. Lon, your miracles give all of us hope! May you find a donor and may you find a CURE! Best of luck to you; so glad things are now looking up!

  6. Lon,
    My positve thoughts are with you. Let your intellect and wisdom guide you. Ive always admired your input and wisdom. I believe you'll pull through this and enjoy much more time with your new family. Keep thinking, sharing and suggesting new things for your treatment. EXPECT the best Lon...Im expecting it for you too.


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