The Freelite© Chain Assay

Myeloma is not always easy to assess. In many cases, the usual types of tests don’t reveal anything useful. For some of us, such as for me, the only laboratory test of value is the Freelite©, which measures the numbers of light chains in serum and calculates the ratio between the two.

I have no problem with the test except that patients often think the ratio has meaning.

Back in 1998, when I was diagnosed with multiple myeloma, there was an older test for light chains, but it wasn’t usefully accurate. I took it regularly and charted its results, but doing so was more for curiosity than for practical application.

Every perfect plasma cell has attached to it two light chains. I find the pictures don’t help a lot, but I’ll add one (above). The light chains are called Bence-Jones proteins after being discovered many years ago by a doctor of that name.

Usually, a myeloma patient will find in his blood both types of light chains, with one abnormally high: kappa or lambda (don’t get frightened by the mathematical-sounding names: they happen to be the initials of the people who discovered them, K and L). They tend to break off the plasma cell and circulate. The number of them in the blood is a rough measure of the infiltration of the bone marrow by myeloma. I think of the measurement as a poor-person’s bone marrow biopsy: it’s as close as we get to measuring something called “tumor burden” in other cancers. Some of us, like me, have no other way of measuring what the cancer is doing. Others, the true non-secreters, don’t even have light chains and must rely on biopsies.

The problem with measuring light chains accurately is that they are stunningly small. Their weight is given in Daltons, which, if you didn’t know, is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of 1.660538921(73)×10−27 kg. Light chains of type lambda are heavier (bigger) than of type kappa, which is why people whose type is lambda may have more kidney problems than kappas. The lambdas are more likely to clog the kidneys (drink lots of water).

A light chain is a VERY small thing.

Then two or three Australian scientists got an idea. After looking at the inaccuracy data of the old test, they thought they discovered two things. First, if the measurements of kappa and lambda were not correct, at least they were incorrect in the same way. That is, both measurements were either too high or too low, never one high and the other low. So they reasoned that if they calculated the ratio between the two types, the result would be accurate and wipe out the error. They even claimed the ratio to be predictive of future relapse. That’s how we got the ratio: to compensate for defects in the original test.

By the time I got one of the authors on the phone, California to Australia, they had recanted on the ratio and its predictive value entirely. Ratio? What ratio? What it actually did was magnify the difference between kappa and lambda so that an observer wouldn’t miss the drop in the non-dominant type, but that turned out to be relatively meaningless therapeutically. If you are type kappa, for example, it doesn’t matter if the lambda drops and the ratio increases: treatment will be the same.

ARUP

Then we got the Freelite© test, which can accurately measure the light chains. In my case, the samples have to be sent to ARUP labs in Utah for analysis, so getting the results takes days, but at least the results are accurate, or, at least, have always made sense for me.

If you go to the Binding Site, who owns the test, here’s what you’ll find about the ratio:

“The serum free light chain ratio is a strong indicator of monoclonality and is valuable for distinguishing monoclonal from polyclonal diseases. “

Actually, the kappa and lambda measurements tell us that already.

Now to be fair, there are a few references to the ratio on the Binding Site, but if one looks further, one can find this from someone worth listening to, Sundar Jagannath:

“One third of patients with monoclonal gammopathy of undetermined significance have an abnormal free light chain ratio, and these patients harbor a greater risk of progression to plasma cell dyscrasia. For monitoring response to therapy, the international uniform response criteria define a normal free light chain ratio as an essential element of the “stringent complete response” category.”

So, if you are MGUS, and the ratio moves but the k/l levels are still normal, perhaps it is the beginning of progression. I think. In any case, CR means a normal ratio in addition to normal levels of kappa and lambda, which, of course, a result we would expect.

Which, obviously, is more than I know about this subject.

SAY HELLO TO EVE!

Eve
After the allogeneic transplant was mightily intensified by an infusion of donor lymphocytes (my donor gave a second time for the DLI!), my old blood and marrow were gone. What I have now grew from my donor’s cells, giving a whole new meaning to the farmer’s tomato-adoring phrase, “home growner.” I can no longer say things such as “my donor is recoloring my hair” because my actual donor isn’t changing my hair: she’s a resident physician in a hospital. So why is my hair lightening for summer? It’s not as if my hair fell out and came back a different color, which happens all the time with chemotherapy: the color, now a golden brown, evolved over weeks.

Again, nothing of my old blood and marrow system remains: blood type A- has become O+; the marrow itself, in nearly every bone in my body, is entirely from my donor, which also means that the blood and everything part of the blood and marrow system—biochemical signaling (e.g., cytokines), clotting, oxygenating, waste disposal, nourishment, and a multitude of other functions of which I know very little. My blood is no longer mine at all, except, I suppose, by right of possession, and most of us can remember how well asserting that principle of law worked out in The Maltese Falcon. (No, children, not the Millennium Falcon.)

Were I to be a trifle careless at a murder scene and spill a few drops of blood, my donor could be identified as a result of a DNA test. In the process, in passing, not of particular significance, I suppose, I also became female, or so saith the DNA. I’ve posted about that already.

This is a fascinating situation for a guy who has been wrangling with myeloma for fourteen years. I thought I had experienced all of it—the whole Borscht Belt of it—but nothing is easy. The problem lies in discourse: my donor is a real person somewhere. She isn’t changing my hair color, or tearing up my fingernails, or demolishing my callouses. So, meet Eve, about whom I can say valid things without inadvertently making a reference to my donor, may she live a thousand years.

This whole subject would be a mere amusement if medical science knew it meant nothing to switch from male to female, A- to O+, live with a foreign marrow, and acquire a completely different DNA profile. However, some differences are significant and observable. I respond to at least one chemo drug to which I had grown resistant (Velcade). Eve is like a new patient who has never been exposed to anything other than the usual childhood diseases and an apple or two. However, because the cancer appears to be gone, I don’t foresee having to use steroids in the future except when it is necessary to hold down the graft-versus-host-disease (GVHD), and certainly I’ll need no chemotherapy. Eve doesn’t have multiple myeloma. Over time, Eve is likely to drop many of her make-over projects as normal becomes redefined (e.g., when she stops hassling my liver).

But interesting thoughts return, probably of doubtful significance, but fascinating to me nevertheless. Although my donor had different parents, we are, in some sense, twins with identical DNA (I can’t decide between fraternal or maternal twins). Because I test female, she has a twin-sister-like chimera in San Diego who shares no family resemblances: although, as things progress, perhaps in delicate light some changes in me might be noticed. 

My brain is associative more than it is eidetic. I make leap and find connections. But associating names with faces or even the titles of Shakespeare’s plays with their plots is heroic for me. Thank heavens I never forget a voice! (Note that I hereby acknowledge having the most ill-suited form of memory possible for the medical profession.)

So the interesting question, crazy or not, is whether or not Eve is sentient. Is there an awareness somewhere, or is all of what is happening strictly biochemical or mechanical? We’re in terra incognita again, because there are other possibilities than those two. If there is an awareness, surely it lives in the right hemisphere of the brain across the corpus callosum, the greatest bridge ever built by humankind. Eve and I don’t share a thinking process of which I’m aware, so how would she make her awareness known to me, were she to desire to do so? Is awareness the same as identity? (Philosophers please comment.)

There are guidebooks of sorts. When I taught artificial intelligence, I learned from these books: Drawing on the Right Side of the Brain, as well as Zen and the Art of Motorcycle Maintenance. I read everything I could find on what happens to a person when the corpus callosum is severed.

So I told Eve what I wanted in several different ways. First, I simply asked her: she, after all, isn’t separated from me by a damaged brain bridge. One of the lessons of a severed corpus collosum patient is that the left side has to use drawings or photographs or objects to talk to the right side. The right side recognizes items by touch, too. I didn’t tell her what sign she might use to get my attention because I didn’t know. Besides, I was feeling crazier by the second just trying to formulate the question properly.

After Eve

Before Eve

The result was flabbergasting. I keep journals. They are all about 275 pages long, each 6″x8″, leather bound in Italy. Filling one up takes me about two years. My cursive handwriting is more to be deciphered than read. When excited, I ignore the lines on the page, neglect the dots and dashes, halt at spelling errors resulting in scratched-out words everywhere, and, in general, I scribble. However, a few days after trying to ask Eve if she were actually there somewhere, something changed. Suddenly, I was writing at many times my normal speed. The sentences were written much more neatly between the lines, and the result was easier to read. Spelling bothered me not at all—I didn’t even think about it, and had to correct very few words. I could write almost as fast as I could think without giving any thought or energy about the mechanics. The cursive letters were quite nice, for me. This journal, at this rate, will take me about three months to fill rather than two years: Is there a more fitting way to send a writer a message than that? Of course there is always doubt, but to my eyes my journal was a clue-by-four. Knowing how to write is a right-brain attribute.

Yes, I suspect, some of you think there’s no difference between my two examples. One thing I can’t demo is writing speed without a video. One day I’ll fix that deficiency, too.

There are other possibilities than Eve’s awareness that might explain all this, I admit, but Eve’s way was certain to get my attention. One day, I plead, tell me somehow you are there, Eve. A day or two later, I acquired a new ability. I doubt very much if the quality of my writing has improved one jot, but the penmanship, speed, and spelling certainly have (although, at times, I do revert to chicken scratching when reaching for a word I can’t spell).

Other than this bit of strangeness (that I am somewhat embarrassed to write about), I am slowly getting stronger, clearer minded, and more productive, but I can backslide for quite some time when the CMV is active or the GVHD is tearing up my liver. Eve doesn’t respond well to prednisone: she reacts rather rudely to it. However, when combined with tacrolimus, that’s all we have to fight GVHD. Fight the GVHD too hard, it releases the often-deadly CMV virus. Fight it too little and it goes after my liver. We scientist types call this situation a “deadly embrace”, where neither side can find a way to get away from the other without horrific consequences. So we lighten the steroid, the CMV appears, we add Valcyte and up the steroid by 5mg or so, then wait a week. If everything goes the right direction, my doctor lowers the steroid by 5 again and we wait. Eventually, we hope, Eve will tire of attacking my liver, skin, GI tract, and other parts of me and the result will be a return to a semi-normal life.

I ache for that return.

Do These Shoes Make Me Look Fat?

Tiresias

The thought popped into my head unbidden. After the allogeneic transplant in 2010, my chimerism tested 100% donor. In theory, that meant that none of my old blood and marrow remained in my body. In other blood cancers, such as lymphoma, donor lymphocytes (DLIs) are often given after the allogeneic transplant to achieve the goal of 100% chimerism. But I wasn’t 100% donor despite test results that claimed otherwise. The chimerism test simply isn’t reliable for myeloma. Numerous malignant plasma cells were not picked up by the test and didn’t count. But those remaining myeloma cells were clearly mine, not those of my donor. There were a great many of them as well.

Which is why we decided to do risky and exceedingly rare infusions of donor lymphocytes in the hope that they would destroy the remaining malignant plasma cells, which, in fact, they did, while almost destroying me as well. There is no remaining evidence of cancer, and today I probably am 100% donor (my fingernails probably have my original DNA, but for how much longer I can’t say).

So I sent an email to a couple of hematology fellows that read something like this, brevity being the soul of wit:

If I accidentally dropped a little blood at a murder scene, would my donor be arrested?

Ok, I forgot, I’m sorry! Big teaching hospitals support a stunning number of lawyers, and they and the n00b fellows, whom I like quite a bit, apparently missed or discounted the humor. There was much consternation and consultation, I am told. I can’t help it. I’m a writer. When I want maximum attention I know how to get it. Besides, when my sense of humor returns after a long absence, it’s a signal that things are going right. They’re still talking about my email days later.

So after a few days, when institutional sanity was more-or-less restored, I got the answer to my question. If my blood were to be tested, my donor would be revealed from the DNA. In fact, were my blood DNA tested today for sex, I would be found to be genetically a woman. Oh, my, whatever does that mean?

I don’t know. I’m not sure anyone does: I’ve been in terra incognita since the DLI. Every cell in my body is now being nourished by my new system (or, more accurately, my donor’s reconstituted system): my immune system is hers, my marrow is hers, the deep and pervasive chemical signaling system is hers, and she clots my wounds. Of course, the hormone balance is mine, so there are no visible or libidinal transformations taking place. But I have to wonder: with my brain cells bathed in her blood, am I changing in any detectable or meaningful way? Blood isn’t simply a letter designation on a bag of cells with no significance other than in transfusions. The working title of my book has been “My Inner Woman is a Lesbian” since the beginning, and its resonation now is a surprise.

So I asked my Facebook friends about this unanticipated turn of events, as, indeed, I ask you, my dedicated readers, for advice on the signs of transformation for which to look and how I should respond to them should they appear. After all, if Facebook friends can’t give you an answer to a complicated question in less than a minute, there is no answer.
From Cindhi:

Do you now or have you ever loved shopping? Dangly earrings? Sparkley sandals? Would you prefer a stout or a cosmopolitan? Do you crave hot wings or chocolate covered strawberries? Only you and your inner donor know the answers.

From Jack:

As a fellow MM patient and recipient of female stem cells for my allo, I’ll just say “Wait for those monthly mood swings!”

From Lynn:

i want to have a bitch session with you:)

From Susanne:

lol. I’m sorry Lonnie but I giggled when I read this. YOU COULD BE THE ULTIMATE CRIMINAL! :D hahahaha However I’m so happy you’re feeling better than I don’t really care if you’re turning female :)

From Mike:

….and just think of this bonus Lonni; you will now recall everyone’s birthday and anniversary! (and I heard your donor lady is a Christian and a conservative Republican!) Hahahahaha Best wishes! 

From Allyson:

sounds like its time for you to see the last mel gibson movie thats it ok for a jew ot see.. what women want shabat shalom 

From Robbie:

LOL Lonnie!!! You crack me up, havent read the blogs in a long long time. So very glad to hear you are doing better, and hey whats wrong with getting in touch with your softer side. Anyway, I dont really think you have to worry about pms or the other womanly problem of menopause. But if you do then thats all the better for us woman right?? A manly man understands women!! 

I can’t find the quote just now, but someone asked me if leaving the toilet seat up was beginning to annoy me. Was I starting to prefer baths to showers? Do I hate my callouses? (My donor does–she removes mine as fast as I can develop them. I’d like to point out that callouses are protective, and doing without them is painful.)

I have noticed that my fingernails are growing in once again, this time gnarly. I am desperate for a manicure. Also, after the DLI my hair appeared to be falling out again. You will recall that after the allo, it returned in my my boyhood color, a chestnut brown with reddish highlights, instead of the standard-issue salt-and-pepper gray, so, what next? Just bald? Well, I didn’t go bald. Instead, I went thinner, went thicker, and now am a blonde. Extraordinary. What next? Does ear piercing hurt?

The Hybrid Man

A, B, O, AB. If you are someone like me, who wishes Grey’s Anatomy to end soon and forever (if I thought any medical staff behaved like the staff of Seattle Grace, I’d never go near an hospital again), then you’ve also heard, when transfusions are involved, the order to “type and crossmatch” the blood. You know that mixing types can be dangerous. There’s more, of course, but who cares? I can remember sitting with groups of friends who, for whatever reason, revealed their types. “Oh, you’re type A? I’m AB positive!” “How interesting!” Pause. Change of subject.

Ignore these meaningless facts

The classification of blood into types omits everything truly important about blood, which, in my experience, has a little-known dimension that, for those of us who must live in it, is overwhelming and mysterious.


I refer specifically to the few of us who have had allogeneic transplants from matched but unrelated donors (a MUD) and have achieved 100% chimerism (meaning, our birth blood and its generating marrow have been completely replaced by that of the donor).

My donor should be about twenty-five or twenty-six by now and is a woman. I know this because they told me. That’s all I am allowed to know for the first year–the sex and age of the donor.

My first inkling of the profundity of the MUD came when, after the allo, my hair grew back—not the salt-and-pepper gray that it had aged into, but its original chestnut brown with reddish highlights: my boyhood colors! I hadn’t imagined such a possibility. How is that possible? Where is color description stored in the gene sequence?


Then my fingernails started to improve. They became thicker, smoother, and better formed. They stopped splitting and breaking. I have new, improved nails. I have no doubt whatsoever that my donor is female.

The callouses came off intact (photo not of me)

Next was something not pleasant: my donor and lifesaver didn’t like my callouses at all, so she removed them. Off the palms of my hands came intact disks of callous, looking rather like the heels on a man’s leather shoes when removed. It was an unnerving process. Fingertips. Feet. Everywhere. I was surprised by the volume of material removed. Callouses are there for a reason: to protect what they cover. Without them, my hands and feet hurt. I also lost the callouses on my fingertips: I used to be able to reach most intervals of a tenth on the piano (an octave and two notes), but some of them just barely, and now I can’t reach some crucial ones. Which means, the piece I spent almost a year learning and improvising, Gershwin’s Prelude 2 in C# minor, I can no longer play. Bummer. I want those few millimeters back! (Click on the MUSIC tab at the top of the blog and you will find my early recording of the Gershwin, before I spent so much time making it my own. I wish I had had time to rerecord it.)

On the last day of November, 2011, I had an infusion of my donor’s lymphocytes (DLI): the allo had given me a year of partial remission and good quality of life but was failing. A series of DLIs was the only option that might give me a chance at long-term survival: however, the chance of getting the needed reaction from one DLI was less than 5%. In myeloma, it usually takes between four and five DLIs over an extended period to achieve whatever benefit the recipient is going to get, if any. I was told that I’d have the infusion one afternoon, take a nap, and then go home. Perhaps in a few weeks I might notice a change, I might not. Nothing untoward was expected.

Before proceeding, I should make clear just how rare a DLI infusion is for multiple myeloma. For example, the Scripps Blood and Marrow Center (BMT) at Scripps Hospital has been in operation for more than thirty years. They have performed perhaps tens of thousands of transplants of all kinds, including allogeneic transplants for myeloma. However, in all those years, there have been only three myeloma DLI patients at Scripps. The first one died almost immediately. The second survived, but the donor cells attacked him mercilessly for the rest of his life. I am the third. Three in about thirty-two years. The reasons are many: insurance (Medicare won’t pay for it), risk, and “First, do no harm,” just to name a few. DLIs are often performed for lymphoma, where they are far more predictable and much less dangerous. So DLI infusions are not rare in general, but are quite rare in myeloma (Holland and Britain do more of them). In America, they must be performed in a clinical trial in a research setting. I’m also quite sure that the cost of treating me for myeloma since 1998 is well over $1.3M.

The wholly unexpected reaction began the next day with a week in the ICU in complete misery and deliria. I think I was in hospital for a total of twenty-three days recovering, and, even then, left early because I wasn’t going to spend the last holiday season I might have in hospital. The graft-versus-host disease (GVHD) hit me like a cruise missile: I was lucky to have survived. I shrank down to 145 lbs, a ghost of my former self, and I was too weak to walk. Yet, and this is the astounding part, the DLI eradicated the cancer: I got the perfect result, complete remission, on the first try. (In myeloma, if the patient doesn’t achieve complete remission from the DLI, it will have done him little good.) According to the data I have, if I ever see myeloma again it will be years from now–and there is a chance I may actually be cured of it. For a myeloma patient, to get that chance, they must be prepared to die in the attempt. It’s not an unlikely outcome. I saw it as a choice between a year of dying and the possibility of cure. If it is possible to purge the emotion out of the decision, it’s a no brainer for someone with an otherwise good life. Once more, against long odds, I was given (and survived) the best response for which I could have wished. There are times I feel like the luckiest unlucky man in the world.

The GVHD was necessary to destroy the cancer but was almost more than I could bear. I was going to title this post, “Let’s Talk Testicles,” largely because mine had swollen into one huge ball that gave me the most pain of my fourteen year battle with myeloma. Because I had become incontinent, I had to be cleaned up often, and I suspect my screams could be heard for quite some distance. I was surprised by the nurses who cleaned me up. I thought that senior nurses would have seen or done everything imaginable or possible, and as a result would be incapable of being thrown off balance; but when it came to being gentle with my flaming-red beachball, they were clumsy. Finally, I had to insist that I would do the maneuvering myself during cleaning: I had feedback so I could be gentle. If you’re not squeamish or underage–you’ve been warned!–click here for a picture of some other poor sod’s uni-testicle. My skin looked far worse than his, including a blood red tint. Few thought I’d survive.

I did not anticipate having to endure yet another extended period of rehabilitation, but the DLI made me as weak or weaker than I’ve ever been. I hate rehab. This is my fifth rehab, and, in many ways, the most difficult and frustrating. Although I am getting stronger every week,  I still can’t get up from a toilet seat without having a riser on it with handles. I am not a patient man. I can be impatient longer than just about anyone else, but that’s really not the same thing at all.

But I digress. I’ve written and stored seven posts, which cover the aftermath of the DLI, but my mind took a big hit and I’ve been incapable of editing. So they’re leaking out a bit into this one. When my mind is fully clear again, I’ll see if any of the gibberish I wrote is salvageable.

My donor changed my blood type from A negative to O positive. That’s the meaningless part. All remnants of my former blood/marrow system are gone and what I have now came from her. I have her blood, her marrow, her immune system, and the blood-bourne biochemical system that sends signals from the brain to the organs and back to synchronize and regulate their activity. My donor and I cohabit this body. Apparently, I’ve taken on a roommate: a delightful roommate for the most part, but also a mysterious stranger whom I am slowly and indirectly getting to know.

One thing I’ve noticed is that I react to drugs differently than before the allo and the DLI. For example, I had become resistant to Velcade before the allo, but responded to it between the allo and the DLI. Some drugs seem stronger, others weaker. However, one must somehow factor in that there are now fourteen drugs I take every day. Because I responded to Velcade after the allo and before the DLI, the Velcade response is valid. When I had had courses of Velcade before, they were not terribly difficult for me to endure. Not this last time. My donor didn’t like them at all. I skipped the final infusion in the series.

Food tastes different, and I seem to want a better diet. I think my donor may prefer a more healthy diet that I do, yet I find myself eating more fruit, more vegetables, less bread, and less meat, and I want everything to be fresh and natural. This is not me. This is she. (At the moment I’ve lost my ability to taste salt, so it’s difficult to enjoy anything but fresh fruit: everything else tastes like chalk. Supposing I needed another challenge to take my mind off of rehab, enduring for more than six weeks now, the children gave me the worst head and chest cold I’ve had in years, so my sense of smell isn’t working right either. I can distinguish sweet from sour.)

I sleep better. I need few if any sleep aids. I go to bed, fall asleep, wake for a bit in the quiet middle of the night, then sleep until about 6:30, when the house awakens for school. I’m not restless: in the morning I feel rested. This is not me either. Before the DLI, my dreaming was impaired. Now I have the normal, refreshing kinds of REM dreams that are profoundly important to having a feeling of well-being during the day. The dreams I have now are much more vivid and powerful.

After the allo (summer, 2010) my skin became new, moist, supple, and young. After the DLI I’m a mess of thin skin, bruises, shiny jet black scabs that linger seemingly forever, and am distinctly red in color. By the way, I’m having my hair done again. She thinned it out last month (I thought I was going bald again), then turned it a very light brown, almost blonde. I have no doubt that my donor is female. None.

Sometimes something seems arbitrary when perhaps it is not. One hundred days post DLI is a milestone of sorts: some call what happens before that period “acute GVHD” and what follows becomes “chronic GVHD.” That may seem arbitrary, but other authorities claim that different processes are at work after one hundred days. At ninety days post DLI I was clearly heading toward normal, except for needed rehab, but at one hundred and ten days my donor recapitulated the GVHD in the precise order in which its components appeared the first time (except, blessedly, for the extreme bloating and the uni-testicle). Right now the callouses I no longer have are being removed again, for example. My skin is paper thin, and as red as my Cherokee ancestors. Pulling off a bandage, like the dressing on a central line, often took my skin with it. What next? I do hope she’ll settle in soon, satisfied with her handiwork.

I wish it were possible to take a timeout. My slowly-improving but powerful disability is depressing and enraging. For a time it included striking memory lapses: I had to be told some things several times for them to sink into my cerebellum and I was often confused. I can’t say,  “I can’t remember what I was told,” because that assertion carries with it the implication that the knowledge is in my head but I simply can’t retrieve it. Not so. I couldn’t recall information because it never went into my head in the first place. I was driving Ivonne crazy. I became angrier and more depressed with every frustration, no matter how slight, and, I confess, took much of it out on her. I don’t sense these lapses now, my mood is much better, and Ivonne is smiling again.

For the most part, I don’t mind the changes. I am apprehensive because someone well known to me (namely, me) has become mysterious and not so predictable. To use the proper King James English, I am become an hybrid. Life is more surprising: truly, I have no idea what may happen next. Every cell in my body is now nourished, tended to, or washed by my donor’s blood, not mine. Her immune system is fighting this head/chest cold, not mine. Mine is gone. It is transparently obvious to me that a MUD followed by a DLI is more than a change of designation (O instead of A-), but has also the most profound and subtle consequences in all of medicine.

P.S. I got a stunning and wonderful letter from my donor this week. I know much more about her now than I did, and much of it is surprising as well as delightful. Next week I will send her the form allowing her to contact me directly (which I believe she will do, but it’s a choice on her part). I would tell you what I know already but I won’t do that without her permission. I teared up often while reading it. But I will quote this from the letter: “Rest assured that as long as I live, I’ll keep donating as much as you need.” Because the system is slow (the letter is dated two months ago), it may be a while before she receives my contact information, so please be patient with me.

We both had the same kind of feelings, apparently. I compare them to those of an adopted baby who first learns that he or she had been adopted when in her teenage years: intensely curious but apprehensive; uncertain as to how to proceed and of the outcome of contact; afraid of rejection. If you can imagine what it would feel like to phone your biological mother for the first time, you’ll understand what I think I and my donor both have been feeling.

My Bucket List

These are very old posts that didn’t make the transition to the new blogger. Putting them in order is going to be  difficult to impossible, but the subject has come up. I think the existing links might still work.

FRIDAY, MARCH 13, 2009
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

Categories Uncategorized

COMPLETE REMISSION: Part 1.5

After 2005 auto transplant  |       After 2010 Allo       |      After 2011 DLI
                    Be sure to click on the photo for the large view.
Today, for the first time since early December, and with considerable assistance, I made it downstairs from the second floor (sixteen steps and a landing), got in the car, then went back upstairs. The went-backing part was considerably more difficult to accomplish than the go-forthing part. Yet I did reach a major milestone, because now I’m free of expensive non-emergency transportation services carrying me at scheduled times to places I don’t always want to go. I can go to a restaurant or see a movie or ride over to Lake Miramar just to feed the birds. Automobiles have always meant freedom to Americans, ever since the Model-T Ford, and, now, I’m finally free again.
The first and second pictures are representative, but the third is not: for those two, all I needed was the photographer. Today, I had a physical therapist (PT) and Ivonne with me, along with a walker. Just out of view to the right is the wheelchair that got me to the spot. In truth, the only time I actually needed something to give me confidence, other than the razor strop the PT tightly cinched to me as if I were a horse, was when the wheelchair had to go down the front-porch steps, but it isn’t cheating if I have Ivonne to help. I could probably have gotten myself out by myself through the garage, but what would be the point? I can’t drive because of the steroids.
The photo also misleads in that I seem to look stronger in the third picture than I did after the allo. After the two transplants, I was much stronger than I am today: the GVHD of the donor lymphocyte infusion whacked me harder than my mom when she caught me smoking. There is also some nerve damage, possibly progressive, that makes doing everything arduous. I can’t walk without mechanical assistance: I need a walker or a wheelchair, and, if the distance is too far, someone to push me. But at least now I can come to a standing position by myself if I have two good, high handholds and have enough sense to wait until my respiration is normal. Tomorrow will always be easier.
On the other hand, this is one of the happiest achievements of my recovery.

COMPLETE REMISSION: Part One

I haven’t blogged since late November, but it’s not because I didn’t want to catch you up on what has happened since then, but rather because I have been physically and mentally unable to do it. Instead, I went ahead with a lymphocyte infusion from a second donation from my donor. The result has been largely unexpected, overwhelming, and quite improbable.

I wrote the whole story this week, but because of its vast length (my longest ever post, something over 2,000 words, so, of course, it had to be shortened if someone else other than myself wanted to read it) and its dark tone (recovery has been, and still is, difficult and dangerous), I’m going to serialize it for emotional consistency.
My allogeneic transplant from a matched but unrelated donor (also known as a MUD), did put me in partial remission, and gave me a year before progressing, a good year. Then came progression. When allos progress, they often progress rather quickly, and, usually, there’s nothing that anyone can do to even slow them down: all chemotherapies are used up; something on the horizon that might help (but not now); followed by a predictable and swift end.
As I’ve alluded to, there is a rare procedure for myeloma, however, called a donor lymphocyte infusion (DLI), which, if it works, can resensitise the new immune system to attack the myeloma.
How often is it done? The Blood and Marrow Transplant Center at Scripps Clinic has been in operation for more than thirty years. In all that time, DLIs have been given to myeloma patients only three times. One recipient did survive for something like another ten years, but I believe the chronic graft-versus-host disease (GVHD) did not make that time pleasant. Another recipient didn’t make it. I am the third. The procedure is almost always one in the context of a clinical trial, and should be.
Although almost routine for other cancers, such as for lymphoma, DLIs are often performed to insure that after an allogeneic transplant there is only one new immune system in the body, the donor’s system, with no remnant of the original (a state called “full, or 100% chimerism”). In myeloma, uniquely, chimerism turns out to have no bearing on the outcome of the DLIs. Another reason DLIs for myeloma are rare is the result is not as predictable as it needs to be to be safe for myeloma: nothing at all can result, there’s GVHD without an anti-myeloma effect, which can be miserable, and there’s death from complications (e.g., liver failure, pneumonia, kidney failure, CMV infections, destruction of connective tissue, alimentary canal damage: the infusion can attack just about anything).

On the other hand, if I didn’t do DLIs, my fate was clear and approaching. Me being me, with a history of phenomenal luck, and after reading the recent journals, I pushed hard to do it. It took some convincing.

There’s no graft-versus-myeloma (GVM) effect without GVHD occurring in less than one hundred days (referred to as “acute” GVHD). After that, if GVHD occurs, it’s called “chronic” and provides little or no benefit. So DLIs, when given, are often given at intervals (of several months or longer) to provoke the necessary acute GVHD response. The average time to ultimate response, if any, seems to be four to five DLIs.

There’s part or me that didn’t want to show you Grade IV GVHD. This is not me, I believe mine was grade III. My skin is red, but returning to normal after exfoliating, my donor must hate callouses, and my GVHD has attacked my liver, skin, and bowels more than anything else.

I calculated the odds from good data for achieving aGVHD on the first shot: less than %5. I expected that there would be no immediate consequences, negative or positive, of the infusion (we were looking for aGVHD to appear perhaps weeks later). In fact, it went down like this: I agreed to proceed on Monday, 28th November; the cells arrived by the next day; on Wednesday they were infused in the afternoon and I went home. By the next day I was admitted to hospital with a horrendous case of GVHD. They doped me with methylprednisolone, to suppress the reactions, which caused serious delirium. Apparently, I was unconscious but active, rolling my eyes around to no purpose, attempting to pull out my picc line (I succeeded on the first one), completely out of it. By that evening I was back in the ICU fighting for my life. I’ll write about that shortly. Of all of four hospitalizations for myeloma, this was the most punishing. Several doctors thought I wouldn’t survive.

Three Days after DLI

But I did survive, and after a few days I was back in my regular room, unable to do anything for myself. Two weeks after the infusion, I asked for a test of my light chains: I wanted to know if all of the suffering I had endured did anything to the cancer. A week or so later, the doctor who pioneered the facility brought me the results, but unlike the five lines I usually see, it was a full page of words. With my head full of steroids, which made reading difficult, I tried to understand what the report was saying: I knew the possible danger of reading into the words what I want to them to say, so it took three times through the realize that the report was saying complete remission. No sign of “extra” light chains. Further, every one of the three numbers was in the middle of the normal range. The cancer was gone. My luck still holds: I got the 5% result, and enough GVHD to fight the cancer without yet killing me in the process (at least, not yet).

I was stunned. When the doctor who has directed the Center for more than thirty years leaned over with a flashlight to look in my mouth, I said to him, “Do you mind if I kiss you?” This guy may be in his seventies, and I must admit it was fun to watch him try to react! He’ll never forget me now. When he demurred, I said, “But you did hesitate!”

After that, I had no brain. All I could think about, when I could think at all, was my impossibly perfect outcome from a single DLI, and the sequence of events that led to it as well as the rapid consequences: immediate response, effective response, GVM, first try. With respect to likelihood, we scientist types like to use the phrase “vanishingly small,” as in, “the probability of that event happening is vanishingly small.” This refers to anything theoretically possible, but with a probability of occurrence so low that it would never occur in the real world. Many of these near-impossible events had to happen to get me to this point, which are on this blog somewhere below.
What do I do with that? The eternal question arises: why me? I feel, probably illogically, as if I have acquired a responsibility, but I’m not sure what it is let alone how to carry it out. In earlier posts I’ve detailed all of the unlikely events from which I’ve benefited, but this latest is overwhelming. The only thing I know I have to do is finish the book, even if I end up being the sole reader.

CR, on the average has just given me another multi-year lease on life without cancer: the present curves suggest five years or more. There is also a non-vanishing possibility that I’ll never see multiple myeloma again.

Last Wednesday I spent hours in the hospital, as I have to do once a week. When they wheeled me into Hematology on my wheelchair, for some reason I was left in an open space for a time. During that time all but one of the doctors who had treated me walked by and said hello (the other one I saw earlier). I’m guessing it was a shift change, but it was then I began to realize that my survival is a huge triumph for the doctors and nurses, too.

Next post will tell you about what the DLI did to me and is continuing to me. I thought that after the allo in 2010, nothing could possibly be as difficult from which to recover. I was wrong.

A Reason for Hope!

I perked up considerably this week when I heard that my young donor has agreed to donate again! In fact, she will be making the donation on the eighth of November, and the cells, on ice, will be flown to San Diego the following day where they will be divided and frozen. So, in about a week I will receive my first lymphocyte infusion (DLI). Cure is still a possibility!
We do have sufficient cells left over from last year’s transplant for one big infusion, so my continuing survival wasn’t entirely riding on the decision of my donor. However, a one-time, big infusion (which is how donor lymphocytes were given originally) could very well have given me severe graft-versus-host disease — even to the point of being fatal. While we have to have GVHD to have a graft-versus-myleoma effect, the risk of a big dose is unnecessary. If given periodically in lower doses, DLIs are just as likely to produce a response but are much safer. We could have gone with the Big Dose weeks ago, but I thought asking for another collection was worth the risk of delay. I wasn’t terribly worried that she (my donor) would decline to donate a second time: people who have actually donated, and not just registered their intention to do so, will almost always do it again if needed.
I must tell you, my life has been bleaker and more desperate in the last few weeks. The reaction to Velcade and Decadron, my reinduction chemotherapy, has been horrible. By the end of the cycle, I had deteriorated so much that I was predicting to Ivonne that I would be in hospital within days: I had become so weak that I could do little but lie in bed; neuropathic pain forced me to take six times my usual dose of pain killers (which blunted but did not control the pain); I did not want to eat; I would sleep for a few hours, wake up for an hour or two, then return to sleep. Because of an episode in early 2011 of tardive dyskinesia  after taking a tiny bit of Seroquel, I no longer am able to use a small dose of a major tranquilizer as a sleep aid. Eyes Wide Open!

The worst part was going through the agony of chemotherapy with little hope of success. My cancer had become resistant to everything but dangerously-high levels of dexamethasone by 2009: why should it be anything other than more resistant now?

And there’s the surprise: this week’s measurement demonstrated a significant drop in the level of cancer. A chemotherapy that failed me years ago is now working. This is wonderful news because the likelihood of achieving remission after donor lymphocyte infusions is greater if you demonstrate a response to reinduction chemotherapy!

The right eye is damaged. Click for larger view.

Not all the news is good, though. Myeloma has attacked my right optic nerve in the form of non-arteritic anterior ischemic optic neuropathy (AION), a devastating disease leading to blindness. I have some vision at the moment, but not much. The left eye has not been attacked thus far, but both eyes are often affected. If I make it three months without losing the left eye, I will probably be safe. The only thing that can be done to protect my remaining eye is to fight the cancer, which is something you can safely bet that I’m doing.

Since recently accepting that I had fallen out of remission after the allogeneic transplant, I have had to also accept the likelihood my impending death (median survival at progression, 4-6 months). I’ve been addressing all of the pressing things a dying person has to do to make life easier for those he will leave behind. I’ve been once more thinking about my Bucket List, although it is much emptier now than when I first wrote about it years ago. But the sadness was inescapable. I had the the sense that most of the things I thought important to do would be for the last time. For example, I’ve been showing Ivonne my favorite movies (Casablanca, African Queen, Lawrence of Arabia, etc.) being quite aware that I would never be seeing them again. I’ve been teary. I’ve worked hard to be a good father and husband, protecting my family and guiding them. I’ve been in the arena with Death for so long now I’ve become inured to my inevitable defeat: I’ve fought the best fight I could, which is comfort enough. I grieve rather for the sorrow and hardship I will leave behind.

Well, screw that! The game’s not over yet! The oppression on my heart has lifted. Cancer, I’m ready for you. Take your best shot! You are MINE!

Border Tales, Part 1: Advance Parole

The little brown man in the dark blue uniform stared at me with steady eyes that revealed absolutely nothing: they very well might have been buttons sewn onto his face. He was small in stature for a Migra (Border Patrol Agent), and old in a weather-beaten way. Despite his stature, I could tell he could put me on the ground in two seconds without breaking a sweat. He said, “There is another paper.” He stared at my face intently, without revealing anything it all, perhaps not even blinking, without impatience, stoically waiting for my response. Time stopped.

My thoughts were racing: I said, “This was the only paper we have!” His response never varied: “There is another paper.” He never took his eyes off my face nor revealed anything in his. My fear was building as I tried to understand what this mistake might mean.

Ivonne, who was going through the immigration process (torture?), had just received a notice of immense importance to us, her Advance Parole. No day was more eagerly anticipated by us than this one. Finally she could go home.

I knew nothing about immigration before marrying Ivonne. I just remember all the war movies that ended with the soldier telling the immigration officer, this is my wife! She’s French! And the officer saying, “Welcome to America!” That image is now quaint. Today the process is expensive, long, and dangerous. From the first moment you file the paperwork, both of you are considered criminals until proven otherwise. Do you like the term, “Advance Parole?” Paroled from what? Some form of imprisonment?

Yes, exactly.

There are two ways a family member can immigrate to America. The longest, most expensive, and most dangerous, is called Consular Processing (CP). In CP, all of the investigations and processing must be done in the foreign country. Further, there aren’t that many places in a foreign country where the processing can be done. For those who live near the US/Mexican border, that means long trips to Ciudad Juarez, one of the most dangerous cities in Mexico, where the US Consulate and associated medical clinics do the processing. It can require years of separation between you and your bride. I didn’t have years.

The other available way, if the alien is legally in America, is called “Adjustment of Status.” (I am becoming annoyed at referring to my lovely wife as the “alien:” she is not green and does not have eyes on the end of stalks.) In Adjustment of Status, along with the form I have to file, the I-130 requesting my spouse be allowed to immigrate to live with me, she can file an I-485 for herself at the same time that that says 1) I’m already here legally;  2) when you decide on my case (Lonnie’s I-130), I ask La Migra to adjust my status to that of Permanent Resident. All processing takes place in America, and it’s cheaper and quicker.

That’s how I brought Ivonne over. She had a long-term tourist visa (B2). This visa is for people who live on the border who need to cross often for shopping, visits to relatives, to doctors, and so forth. They have to own property in Mexico for several years, have a solid work history, pass criminal background checks and have a clean immigration history, demonstrate strong family ties to the border city in which they live, and so on. They won’t give you a visa if they think you might disappear into America with it.

So my new wife and I could stay together until her status was settled. But along with this process comes a terrible restriction: under no circumstances can she leave the country before her case settled. If she did, her visa would automatically expire and be confiscated and she would not be allowed back. Her processing would revert to Consular Processing, which would delay her entry for years.

A few weeks after we were married, for a period of about four months, she stayed here with me. The problem with that was that her father in Tijuana has a couple of chronic illnesses, and her four children were there as well (then aged 11, 13, 14, and 15)! Although all but one had visitor’s visas, and could occasionally visit their mother here, such visits cannot substitute for the care they really needed. If anything went wrong, what would she do? Could she stay here while, for example, her father died or her children were dangerously sick or seriously misbehaving? Where would the children live? Who would look after them? How would they go to and from school? Do the laundry? Feed themselves?

We were very lucky. Nothing truly bad happened. Ivonne’s enormous family took care of the children, their grandfather made sure they got to school (and bought them a lot of fast food), and no one was hurt or seriously ill during that time.

The separation was about to end when the magic paper arrived, the Advanced Parole. She was given permission to leave the country (USA) and return as needed until her case was settled. She could be with her children again! I had set up a video link so that they could see each other and talk, but there are no digital hugs over the Internet. It was a difficult time.

The reason I was staring at the little blue-uniformed man was that this was our first attempt to use her new privilege. We decided to surprise everyone on New Year’s Eve day by first finishing the process (there are things that have to be done at the border before she can just come and go), then crossing a second time to be with the family.

We parked the sedan by the McDonalds on the US side, walked over a long, grueling set of bridges and ramps, then waited in the line to enter the US visa office on the Mexican side. I remembered to bring my cripple sticker with me, so we were allowed to go to the front of the three-hour line where we ran into the little brown man who looked at what we brought, then asked, “Where is the other paper?”

Horrors flooded my mind. We were on the Mexican side of the border with inadequate papers. They might not let her back into America. We’d have to start over with Counselor Processing, adding months or years of virtual separation and thousands of dollars to the process. All the frightening months of enforced separation which we thought were behind us would have been for nothing!

While these thoughts were going through my head, the little man never blinked, never took his eyes off of me, never said a word. I was practically swooning and could feel despair rising. Finally, after long moments, I turned to him and said, with resignation in my voice, “What do we do now?”

This was apparently the right answer, or, rather, the right way to answer. He came alive, took me by the arm, and pointed to a bench across the way: “Go, sit on that bench!” I was confused, bewildered, so he repeated himself: “Go, sit on that bench and wait.” (It should be the motto of the immigration process: Sit Down, Shut Up, and Wait!)

As I wobbled off to the bench, he took Ivonne into the windowless building. It was a cold, concrete bench that gave the impression of never having been used. My future was flashing before my eyes. I was about to lose the luckiest and best thing that has ever happened to me. Would she be deported, her visa confiscated? Would we have to start over? We were newlyweds—when could we possibly be together?

What seemed like hours passed with me in this horrible state, although it was probably more like twenty minutes. Filled with fear and despair, all I could do wait. I remembered the other sheet of paper: it was a duplicate of the one we brought. I thought it was for our records! Ignorant fool! Stupid!

Then, looking for all the world that nothing important had happened, out she came, smiling and calm, as she always appears on the outside when in the presence of La Migra, and as I stood up to walk with her across the border for the first time. I said, “What the hell happened?” She told me that the little man took her to a station where the papers were to be processed. The woman looked over what we had and said, “Where’s the other paper?”

The little brown man replied, “Make a xerox!” then wandered away. That was it. We were free, except for a bit of final nonsense at the actual border line as final checks were made.

We walked to the car, then crossed much more easily a second time to go to her father’s house,  where no one was expecting us. I sat in the car for a time and simply watched as Ivonne and her son, Ruben, each other for the first time in months. Ruben had grown at least two feet and was now, much to her surprise, as tall as she. They stared at each other. She saw a bump on his chin, and said, “You have a pimple.” To say that the reunions were, well, “moving” would be using an wholly-inadequate predicate adjective.

We spent a long time with them: it was the first time we had been all together, and I was to meet Ruben, her son, for the first time. I was reminded of The Lord of the Flies at the moment that Brit Navy finally rescued the children: for a moment, the children couldn’t understand what had happened, and when they finally realized they had been rescued from having to govern themselves, as if they had been adults, they started to cry. They could be children again: their mother was back!

Well, only for a few hours. But now she could travel to Mexico as needed to do laundry, clean house, make dinner, help with homework, settle disputes, all the things that make a child’s world feel safe.

I told the children, in my very poor Spanish, that we would now be bringing them all to America as soon as possible. Ruben, the one boy, is a quiet sort, often seeming to be not part of the group, not perhaps even thinking. But deep inside was a great fear: his father had lost his visa, or sold it, so perhaps he wasn’t going to be able to come to America with the others.

By way of explanation, and I hate to sound racist, but little Mexican boys do look a lot alike. If they have a visitor’s visa, it can be sold to someone, a Coyote, who finds another boy that looks very much the same. They cross the border, $3000 changes hands, the visa is returned to the Coyote, and the process is repeated until they are caught or the visa expires. We suspect his biological father sold his visa. Ruben was stuck in Mexico and had to endure Consular Processing.

Deep inside, he was afraid that he would be left behind. I told him not to worry, the problems with his paperwork in Mexico meant nothing. “I am an American, you are my step-son, I will ask for you and they will agree. Nothing can happen here that will prevent your being with us. There’s nothing your father can do to stop us.” When I explained this to him, and my meaning sunk in, his whole body shuddered as if he were having a convulsion, as relief flooded his body. I even gave him my promise that he would be the first to cross. Mi promiso! That turned out to be a bridge too far: he was actually last. As it turned out, it took a lot longer to bring him to his new home than any of us had imagined, and the process was costly and dangerous, but that’s a story for another time. Today, we are all here in Scripps Ranch, all four are attend great schools, and, as of about a month ago, they made the psychological shift: San Diego is now home for them; Mexico is where they were born. (Can you hear me sigh in relief over the keyboard?)

PS: If I had answered La Migra in some other way, and she had been denied admission and had to restart the with Consular Processing, I would probably not be alive today. When we married, I was in partial remission and doing fine, but two months later it was clear that I had lost all control of the cancer and had little time left. The doctors would not have offered me the allogeneic transplant had I not had an adequate support system at home for my recovery. Fortunately, Ivonne had shown in many ways that she could and would take good care of me, so that never became an issue, insofar as I know, in the decision to put me into a research program for allogeneic transplant in myeloma. I needed more care than any of us had envisioned, and she gave it to me.

Steve Jobs Delayed Surgery in favor of Internet treatments!

Steve Jobs infuriated family and doctors by putting off surgery in favor of alternative treatments. For more than a year, he relied on “fruit juices, acupuncture, herbal remedies and other Internet treatments.” While being one of very few people who have had their cancer’s complete gene sequence identified, he dabbled in medical voodoo.

Even the most rational of us, in the face of a terrifying diagnosis, can act like fools even to the point of foregoing or delaying treatment. I have known well some who shortened their lives by avoiding “chemo” or surgery in favor of treatments of no proven value (and, in the case of immune boosters in Myeloma, may have intensified their disease). My friends have tried all-fruit liquid diets, coffee enemas, magnetic “alignment” machines (Rife), and ruinously expensive quack treatments in Tijuana, just to name a few.

The challenges of effectively fighting a dangerous cancer are numerous. If the cancer is rare, average doctors are often unaware of current research and treatment and still administer VAD, or MP, to a younger patient: they look in the book written years ago, and do what it says. The disease is occult, so we often ruin our quality time obsessing over medical tests during periods where there is no need for us to do so. But the biggest obstacle is the fear of dying: we wouldn’t be human without that fear, but allowing it to drive the decision-making process must be overcome. When a disease is incurable and universally fatal, we, as patients, have a greater right to discuss treatments with our doctors and make choices than do those with common, curable illnesses: this is because all of our alternatives are, in some sense, bad. Pick your poison (rationally).

But too many are like Steve Jobs. Timely surgery might not have helped, but delaying it certainly did not help. Why would an otherwise brilliant man act so stupidly? He let fear (and, perhaps, denial, the other great mechanism for self-defeating behavior in cancer) get the better of him. My book, if I can live to finish it, is about how to embrace fear squarely and disconnect it from medical decisions while also fighting cancer with evidence-based medicine. It suggests ways to improve ones remaining quality of life by giving the cancer as little time and effort is possible.

Right now, in my personal battle, QOL has become an issue, mostly as a result of doctor indecision (but also due to Velcade, dex, and a stupid cold). I did my homework, I know what I want to do, but getting it through the tumor board is proving to be challenging. While waiting in suspense through this infuriating bureaucratic delay, my good time has diminished, but, hopefully, in a week or so, the course will be decided and I can return to fully living my life.

Here’s the story:
http://tinyurl.com/3hhxzl3

www.nytimes.com

A 630-page biography on Steve Jobs also includes previously unknown details about his romantic life, his marriage, his relationship with his sister and his business dealings.