Thursday, December 29, 2011

A Penny For Your Stem Cells

As you may recall, the first big step in the stem cell transplant procedure that I underwent two years ago was the harvesting of my own stem cells. Over a period of several days I was given a drug (Neupogen) that stimulated the bone marrow's production of stem cells, and pushed them out into the blood stream. When there were enough of them out there, they were extracted (a process called "apheresis") and frozen for future use. This type of peripheral blood stem cell transplant, in which I was both the donor and the recipient of the stem cells, is called "autologous". In the other type of stem cell transplant, called "allogeneic", the donor and the recipient of the stem cells are different people. And according to the provisions of the National Organ Transplant Act, the donor must not be compensated for his or her role in the transaction.

The Act doesn't say so explicitly, though, because in 1984, when it became law, neither type of peripheral blood stem cell transplant existed. At that time, stem cells had to be extracted physically from the donor, in a process known as "aspiration" -- the same process I undergo when I get a bone marrow biopsy. It involves anesthetics, and big hollow needles that are pushed directly into the donor's bones. Except whereas just a small amount of marrow is quickly extracted for a biopsy, a great deal more must be taken for a bone marrow transplant. It's a lengthy, dangerous and painful process for the donor, which is why bone marrow donors have traditionally been difficult to come by, and why this older type of bone marrow transplant has been progressively replaced by peripheral blood stem cell transplants. But the anti-compensation provisions of NOTA have been assumed to apply uniformly to stem cells, irrespective of the method of their extraction, even though the law's text necessarily refers only to bone marrow extracted via aspiration.

Until now, maybe. Recently the 9th U.S. Circuit Court of Appeals ruled that stem cells extracted by apheresis are more akin to ordinary blood than to an "organ" -- it has always been possible to pay people for their blood -- and that therefore NOTA does not apply to stem cells extracted via apheresis. It hardly need be said that such a ruling is controversial -- it's thought by some to represent a "camel's nose" for the eventual development of a market in organs -- and is probably headed for final resolution by the U.S. Supreme Court, if Their Honors are interested.

Monday, December 26, 2011

The New #27

At long last I have the long-term replacement for tooth #27. On Thursday I returned to the dentist's office for the "delivery" (official dentist terminology) of the crown. He worked quickly, unscrewing the temporary insert and screwing in the real abutment. As an aside, you haven't lived until a dentist has climbed into your mouth to tinker in there with a wrench, as if he was a mechanic changing the plugs on a mid-size sedan. Fitting the crown required a couple of attempts, with adjustments to the shape made with a grinder. When he was satisfied, the crown came off one last time, and a semi-permanent cement was applied to the abutment. The cement is not the strongest dental cement available, so that the crown can be removed later, if necessary for some reason, without destroying it. The crown was then mounted for the last time, and the cement allowed to set for a couple of minutes. Finally came the most painful part of the process: The dental technician had to clean up the excess cement sticking around the lower edge of the crown, using a sharp implement; this caused substantial irritation to the surrounding gum.

Thus ends the strange and sorrowful tale of tooth #27, about which nothing more needs to be said, I hope.

Friday, December 9, 2011

One Step Removed From The Crown

Progress has seemed glacial all along, but today saw one step closer to the end of the saga of the late lamented tooth #27. I traveled to the dentist's office to have the impression taken for the implant's crown. The man used a grinder on the adjoining teeth to get a bit of clearance, unscrewed the oral surgeon's temporary abutment and replaced it with the real, permanent one, and then stuck an undersized version of your typical caulking gun into my mouth. The solidified result of the squishy stuff that came out of it will be sent off to the lab to be used to manufacture the crown. I will return on December 22 to have it installed.

Tuesday, November 15, 2011

Implant Check

Today I returned to the office of the oral surgeon, to have him check on the implant that he had stuck into my lower jaw in place of tooth #27, back at the beginning of August. After tapping on the abutment and trying to move it around, he expressed satisfaction that the implant and the bone are getting along well with one another, but decided that the gum in the vicinity needed "reshaping". After giving me a local anesthetic, he brought out some kind of small laser torch; shortly thereafter, I could smell my own flesh burning. It's not a scent I would like to become familiar with. I'll have a bit of pain for a few days, but in a couple of weeks, assuming that everything heals up nicely, I'll be ready for the crown.

Saturday, November 12, 2011

A Year At Work

It's a little hard for me to believe that is has been so long already, but as of the beginning of November, I have been back to work for a full year. Upon review, it seems that the concerns I expressed at that time turned out to be mostly groundless. I believe that I am now functioning mostly as I did prior to the beginning of my crisis, almost two and a half years ago. The only differences are that I still have to take the occasional nap during the day (much less frequently than a year ago, though); and of course I have many more medical appointments than before. It remains to be seen how long this period of relatively comfortable stability can continue.

Tuesday, November 8, 2011

Hearing Check

For several years now, when watching a movie on DVD, I have felt compelled to turn on the "captions for the hearing-impaired". I do this in the interest of being able to comprehend the dialogue, which can sound muddy and indistinct. I can simply turn up the volume to achieve the same end, but that makes the music and the explosions too loud. This problem seems to have worsened during the past year or so, so recently I obtained a prescription for a hearing evaluation from my primary care doc. She noted that chemotherapy has been known to affect hearing, and we agreed that in any case it would be good to at least establish a baseline, for future reference, even if there is nothing else to do about the problem for now.

Today I travelled to downtown Wilmington for my evaluation. There was really not much to this; I spent more time filling out forms than I did being tested. The audiologist first simply did a visual inspection, to ensure that there were no physical obstructions blocking the ear canals. She also did some kind of pressure test, in an effort to verify that there was no water in there, behind the eardrums. For the actual test, I was seated in a soundproof room, wearing a pair of earphones and holding a pushbutton device. I was instructed to push the button whenever I thought I could hear any tone, however indistinct, coming through the earphones. Of course I was fed tones at a wide range of volumes and frequencies. Finally, I was asked to listen to and repeat back a number of one-syllable words; these were obviously designed to detect any inability to distinguish between similar-sounding consonants.

The audiologist indicated that the test did not reveal any substantial loss of hearing. There is some deterioration at higher frequencies, which could account for some of my difficulties. But at this point there is nothing wrong that makes intervention necessary or desirable.

Friday, October 14, 2011

The End Of SSDI

At the time I returned to work in November of last year, I was receiving both Social Security Disability Insurance (SSDI) benefits and employer-provided long term disability insurance benefits. The latter stopped instantly upon my return to work, but the former continued during my "trial work period" of nine months, through July of this year. Had I discovered that I really wasn't up to the job of doing my job during that time, I could simply have dropped back into my original disabled status, and SSDI benefits would have continued without missing a beat. At the end of the trial period, the Social Security Administration (SSA) notified me that my case was now under review, the object of which review was to determine just how disabled I was at that point. Benefits would in any case continue during the three-month review period, that is through the end of October of this year.

The SSA has completed its review of my case, and has concluded that I am indeed no longer disabled -- sort of, at least. Benefits will terminate at the end of October, but there is an additional 36-month period (starting from the end of the trial period, thus running through July 2014) during which I can revert to disabled status without too much ado. After July 2014, I will revert to my original virginal non-disabled status, just as if nothing had happened in June 2009; if I become disabled again, I will have to begin the SSDI application process all over again, from Ground Zero, regardless of whether or not the cause of my disability has anything to do with the cause of any past disability.

Sunday, August 21, 2011

Jack Shaffer, R.I.P.

Kind of off-topic for this blog, but it's the unavoidable elephant in the room right now. My father died not long after being taken to the hospital this past Wednesday. Here is the obituary.

He had been suffering a long, slow decline for years, and we were really expecting more of the same for the time being. There was nothing new happening that would have led anyone to predict such an abrupt departure. He did have some sort of stroke event recently, but he seemed to be recovering nicely from that. Huong and I were able to spend a long weekend with him only a couple of weeks ago, when we travelled to Ohio to check up on him. We departed unaware that we had just said our last goodbyes.

Wednesday, August 3, 2011

The Common Rule

The Federal Policy for the Protection of Human Subjects, colloquially referred to as the "Common Rule", regulates federally-funded research that involves doing things to people. All the various departments and agencies of the federal government are supposed to follow the Common Rule, including even the CIA (yeah, right). Last revised about twenty years ago, it is due for some changes, which are currently under review. Many of these changes relate to reporting and auditing issues. Somewhat more interesting is a proposed change to the provisions relating to the disposition of biospecimens collected in the course of such research. Currently, any such biospecimen can continue to be used indefinitely, without the knowledge or permission of the person from whom it was taken, as long as it has been anonymized, i.e., as long as any identifying metadata has been stripped from the specimen.

But since the time the rules were last revised, the field of genomics has developed the ability to identify the individual source of any biospecimen, based on the DNA it contains, increasingly quickly and increasingly inexpensively. In effect, the biospecimen is its own identifying metadata. So the new rule in this area would require that any biospecimen collected in the course of a federally-funded research program must be destroyed at the conclusion of said program, unless the human source of the specimen has explicitly granted permission to retain and/or distribute the specimen for further use.

In my case the point is moot, since I granted such permission when I added myself to the Rare Cancer Genetics Registry.

Monday, August 1, 2011

R.I.P. Tooth #27

Today I crossed the Rubicon and travelled to the oral surgeon's office to have #27 yanked and replaced by an implant topped, for now, by an abutment that will eventually carry a synthetic crown. The whole operation took about an hour and caused, at the time, no pain whatever. Now that the local anesthetic has worn off I'm substantially less comfortable (codeine Tylenol to the rescue), and the crater left by #27 is exceedingly ugly. Now there is nothing to do but wait for the wound to heal and hope that none of the possible negative consequences show up.

Sunday, July 17, 2011

Recent Developments

This past week the oral surgeon received the results of the CTX test, so I travelled to his office to discuss the situation with him. My score on the test was 175; anything over 150 means that the risk of ONJ is minimal. He is therefore willing to extract #27. We discussed the replacement options, all of which strike me as unpalatable (pun intentional), other than the implant. Of course an implant carries with it risks of its own: the bone may not bond with the implant; the gum may not heal and/or may become infected; nearby teeth, nerves or muscles may suffer collateral damage. Having watched the educational video on the subject, I scheduled the extraction for August 1. Gulp.

Meanwhile, the oncologist has changed my chemotherapy regime. We discussed the concerns about prolonged Revlimid exposure leading to additional hematological cancers, and he offered an alternative protocol involving a lower dose, in exchange for giving up the one break week in four. I'm going for it. I'm hoping that eliminating the break week will allow my digestive tract to figure out what it is supposed to be doing; after more than a year, it has never gotten used to the switching on and off. The old 25 mg Revlimid capsules were large white oblongs; the new 10 mg capsules are smaller, half blue-green, half pale yellow.

The oncologist took the opportunity of this discussion (and the recent two-year anniversary of my diagnosis) to remind me that, although the trials establishing Revlimid as a maintenance therapy showed significant delays to post-transplant progression, they could say nothing about its ultimate effect on survival, vs. waiting for progression before hitting the cancer with it. That's because they stop too soon to show that. One would have to drop Revlimid on the patients in the placebo group after they showed progression, and then continue to follow the entire group until death. No one can wait that long to find out the answer, so I am part of the de facto clinical trial that will ultimately determine it.

Friday, July 1, 2011

The CTX Test

Having successfully petitioned the oncologist to suspend the Aredia (IV bisphosphonate) therapy, earlier this week I presented myself in the office of an oral surgeon, who concurred with the endodontist's diagnosis of external root resorption in tooth #27. If he is to perform an extraction, he insists (as the endodontist predicted he would) on a CTX test to gauge the risk of osteonecrosis of the jaw (ONJ) arising from the bisphosphonate therapy. Of course an oral surgeon has the power to write a prescription for this test, so he sent me home with such.

Ordinarily, if an MD gives you a script for a blood test, say for a lipid panel (cholesterol check), you just take it to a local outpost of LabCorp or Quest Diagnostics. After a little dance involving making copies of your medical insurance card and a photo ID, and signing a form agreeing to pay if the insurance company for some reason declines the honor of doing so, your blood is eventually drawn into one or more little tubes, and some days later the results are transmitted to the doctor's office. That's the basic business of these giants of the medical-industrial complex.

Things are a bit more complicated for a cancer patient. I once tried taking my monthly script to the nearest LapCorp site. Of the three people who happened to be working there at the time, only one claimed to have any idea what the script was talking about. He happened to have worked in a cancer clinic. He said, "Yes, I'm pretty sure we do that, but...". But the logistics surrounding getting the blood sample to the right test lab were such that I could be given no reliable ETA for when the results would reach the oncologist's office. No sale. Instead, although it's a longer drive, I always take this script to the lab in the cancer center; for them, this test is routine, and is reliably turned around within 48 hours.

The cancer center lab waved off the CTX test, which surprised me a little; but then, the oncologist had told me that he has no use for it in his practice. The oral surgeon was pretty sure that Quest could do the test, which I confirmed with a phone call to the nearest Quest site. However, when I arrived there, to my surprise, my insurance card was rejected; the test would be done only if I presented a credit card. So: One of the largest providers of medical diagnostics in the country won't play with one of the largest providers of medical insurance in the country. Love this system.

On the way home, I stopped at the LabCorp site. "I've worked here for seven years, and I've never heard of this test." A phone call to LabCorp customer service confirmed the technician's fear that he couldn't do the test.

My next thought was to discuss the situation with the medical insurance company. What would happen if I paid Quest to do the test and then submitted a claim? But before I did that, another question occurred to me: What if the CTX test really travels under a different name -- a more technical-sounding name that people preferred to abbreviate as CTX? A few moments with Google provided the answer: The CTX test is really the "C-telopeptide serum" test. There is an even longer, more technical-sounding name (the name from which "CTX" actually comes), but I took "C-telopeptide serum" to the test menu on the LabCorp web site and, lo and behold, there it was. Just to be certain, I verified with the oral surgeon's medical assistant that this really is the test I was supposed to get.

This morning, I journeyed back to LabCorp, this time armed with the LapCorp test number for "C-telopeptide serum", and was in and out of there in minutes. All I have to do now is wait for the oral surgeon's reaction to the results.

Monday, June 27, 2011

Rare Cancer Genetics Registry

In the wake of the tremendous progress made in the field of genomics over the past decade or so, research into the genetic underpinnings of the diseases collectively called "cancers" is hot. Genetic flaws -- missing genes, extra genes, transposed genes -- have been implicated in a number of different cancers. Worldwide, researchers are racing to add to this store of knowledge.

Meanwhile, Congress occasionally frets about the fate of victims of so-called "rare" cancers which, collectively, add up to about 25% of cases and deaths. Because of the relatively low number of patients having a given rare cancer, it is difficult to populate clinical trials relating to the disease, and a drug targeting it is difficult to deliver in an economically viable manner. Hence, for example, the Orphan Drug Act, which is meant to short-circuit the ponderous FDA approval process for drugs targeting rare diseases, thus making their production more attractive to the pharmaceutical industry.

A couple of years ago, the National Cancer Institute funded the establishment of the Rare Cancer Genetics Registry, which is meant to be a storehouse of the raw materials necessary for research into the genetics of cancers such as multiple myeloma. The registry contains a database of patient family medical histories, pathology records, and DNA samples. Researchers have the ability to obtain tumor tissue samples, and to contact registrants regarding voluntary participation in studies.

Earlier this year, I received from Johns Hopkins, which is one of the research and recruiting centers of the registry, an invitation to participate. It took me several months to round up all of the required family medical history information (this is how I learned that Grandpa Shaffer's "bone cancer" was really metastatic lung cancer), but a couple of weeks ago I finally sent in the completed questionnaire. Today I sent in my DNA sample, in the form of a tube of saliva.

It is possible, but unlikely, that my entire genome will be sequenced; far more likely that only those portions of it implicated in myeloma will be cracked open. But of course if over time more of it needs to be examined then it will be available for that purpose. In any case, the results of none of this activity will ever be available to me personally. There is no predicting when, if ever, I could be asked to participate in a study, or what such participation might involve in terms of personal commitment. But at least now I'm in there.

Saturday, June 11, 2011

Back On My Bike

Before my first trip to the hospital, almost exactly two years ago, I was fairly physically active. I was doing some running (actually running wind sprints) and biking, and doing some light weight training. All this came to an abrupt end, of course, with the onset of my crisis. Since then, once I recovered (more or less) my ability to walk, walking has constituted almost the sole form of physical exercise for me. I use a treadmill or, if walking outside, I continue to use the cane as a safety device. Probably, I will never run again, since that would risk injury to the fragile, disease-ravaged spine. I find the idea of water exercise fairly tempting (I swam for years, back in the day), but fear the chlorine (eventually the irritation it causes the skin becomes unbearable, which is why I stopped swimming in the first place).

But then, there is the bike. This year I was determined to give it a try, once the winter broke. I wasn't completely confident. The muscles used in riding a bicycle are different from those used in walking, and they hadn't been used in a long time. There remains substantial numbness in the lower half of my body, so I wasn't exactly sure how well I would be able to control the vehicle. And once one's feet have left the ground, there isn't a lot of room for error. A fall would of course be fairly calamitous.

The transmission on my bike is 24-speed, so it can be cranked down to a point where, on a level surface, very little force (but a lot of pedaling) is required to achieve forward progress. I assumed that I should begin with this configuration, not knowing how much force I would be able to apply. I wasn't even completely certain that I could remain balanced on the thing. But as it turned out, things went better even than I was hoping. I was able to advance the gearing (but still considerable below the old normal) and ride up and down the street some way a couple of times. I was very happy with the results of this first attempt. I certainly could feel the fact that I was waking up muscles that had been asleep for a long time.

Since then, I have made a lot of progress on this. I can ride several miles, negotiating steep hills, just as before, albeit at a much slower pace. I can feel my strength and stamina improving. I'm not sure it will ever be the same as it was, but that seems hardly to matter. For now, I can just enjoy the ride.

Monday, May 16, 2011

Reefer Madness

Last week, Delaware Governor Jack Markell put his signature to the state's first medical marijuana law. Of course, cancer is at the top of the laundry list of maladies that qualify patients for participation. I guess it's time to go shopping for a nice bong...

Kidding. For a state that trends to blue politically, Delaware is relatively socially conservative, and this is reflected in the fact that the law is substantially more restrictive than those currently in effect in, say, Colorado or California. Patients are not permitted to grow their own, and must obtain their smoke (a maximum of six ounces) from one of only three non-profit dispensaries (presumably one per county). Patients must have an on-going relationship with the prescribing MD; are supposed to have exhausted all the standard alternatives; and must obtain a state-issued ID card. It remains to be seen just how much of a problem there will be with people with nasty hangnails showing up at the dispensaries with ID cards and prescriptions, since there is an escape clause covering individuals with unspecified "chronic" and "debilitating" conditions. On the whole, it all sounds a lot more inconvenient than just driving to certain Wilmington neighborhoods on Friday night, but I guess that's partly the idea.

Huong asked me how interested I am in this. The answer is "Not Very", at least for now. I am not currently taking any kind of pain medication, not even any of the OTC varieties (OK, yes, I'm taking 81 mg aspirin, but that's for the heart, not for pain), and I'm hoping to avoid having to do so for as long as possible. The prescription opioids (e.g. Oxycontin) render me hopelessly constipated. I guess if it ever comes to the point where I'm pretty desperate then I'd consider smoking up. Actually, I'd prefer not to smoke it; I'd probably invest in a nice vaporizer.

Saturday, May 14, 2011

Minus Aredia

The oncologist did not require much in the way of persuasion to call off the Aredia treatments for the time being, in honor of my recently discovered need for oral surgery. But he did question the need to order any CTX tests, indicating that it should only be necessary to wait a decent interval before proceeding. That was not the impression I had gained from what the endodontist had told me, so these two titans of medicine will consult, and presumably arrive at some kind of consensus on the subject.

This month, in addition to the usual blood tests (results as usual), I got a 24-hour urine test. This is really just looking for the same monoclonal proteins as the blood test, but is much more sensitive. It, too, failed to turn up anything. I also got a skeletal survey, which revealed little change since the last one I got, around a year ago. So everything is indicating stability at this point.

Recently it has seemed to me that the abdominal bloating has gotten worse, and I occasionally experience pains on the right side. Next week I am scheduled for an abdominal ultrasound, to check into this situation.

Monday, May 9, 2011

An Unexpected Complication

I seem to be specializing in Strange Maladies Of Indeterminate Origin. Last week, I visited my dentist for a routine cleaning and examination. I also got the annual full set of X-rays. The picture of one of the mandibular canines (tooth #27) caught the attention of the dentist, who forwarded it to an endodontist, who delivered a diagnosis of external root resorption. This is a poorly understood (especially by me) phenomenon, in which the tooth appears to be destroying itself from within, "apparently initiated by a peculiar inflammatory hyperplasia of the pulp", by one account. This could be an autoimmune disorder, but it is more commonly believed to be ultimately caused by trauma, where "trauma" is defined to include the wearing of orthodontic appliances -- which I did, back in the day. If the damage is not too advanced, the tooth can be rescued by means of a root canal; otherwise, it must be extracted and, nowadays, typically replaced by an implant. In my case, the endodontist would normally pass me off to an oral surgeon for extraction. But...

But I am receiving bisphosphonate therapy, to counteract the effects of the cancer on my spine. Normally, special cells called osteoclasts clean up old bone mass, making way for new bone created by the counterpart osteoblasts (a process known as "bone turnover"). Myeloma appears to overstimulate the osteoclasts, which begin to outperform the osteoblasts, creating many lytic lesions -- holes -- in the bone. This is obviously a Very Bad Thing, leading in my case to a greatly enhanced risk of spinal compression fractures. Bisphosphonates such as the one I am getting, Aredia, attempt to solve this problem by suppressing the osteoclasts, which is a mixed blessing, since bone turnover is as a result reduced everywhere, meaning that the bones are more brittle and are slower to heal than they should be. Apparently, this is especially a problem where surgical procedures performed on the jaw, such as a tooth extraction, are concerned, leading to a condition known as "bisphosphonate-related osteonecrosis of the jaw". The wounded jaw does not heal, and eventually the bone in the vicinity of the wound dies. This is another Very Bad Thing. So oral surgeons are understandably reluctant to perform extractions on patients receiving bisphosphonates.

The effect of bisphosphonates on bone turnover is typically gauged by a serum CTX test; patients getting bisphosphonates will show much lower than normal CTX numbers. A sufficiently lengthy drug holiday might return serum CTX to a range acceptable to an oral surgeon; a temporary root canal might be necessary to stave off disaster in the interim. The question is whether the oncologist can be persuaded to declare such a drug holiday. I was on track to continue receiving Aredia until at least the end of this year, for reasons of course completely unrelated to dentistry. My next visit with the oncologist should be much more interesting than usual, for this and certain other reasons, which I will discuss in due time.

Sunday, April 24, 2011

The Safety and Effectiveness of Revlimid

A few weeks ago, the FDA issued a safety announcement concerning Revlimid, indicating its concern that longer-term exposure to the drug increases the risk that the patient will develop additional hematological malignancies (translation: leukemias and lymphomas). This isn't exactly shocking new news, but it does betoken a heightened level of concern and awareness of the problem. Of course, in my case, "longer-term exposure" is exactly what we are hoping for, since the idea is that I will continue to take Revlimid as long as possible, until it stops working.

But we already knew that the answer to the "how safe" question is "not very". Lenalidomide (Revlimid's chemical name) is a derivative of thalidomide, which was originally introduced in the 1950's as a sedative. Thalidomide was prescribed to large numbers of patients, among them pregnant women, who proceeded to produce tens of thousands of babies with severe birth defects, until the drug was withdrawn in the early 1960's. It was one of the most spectacular failures in the history of the pharmaceutical industry. But in the 1990's, thalidomide was resurrected as a chemotherapeutic agent effective against none other than our old friend, multiple myeloma. Subsequently a derivative, lenalidomide, was introduced for the same purpose, but with better responses and fewer side effects for many patients. Today, both thalidomide and lenalidomide are being prescribed for myeloma, but they are distributed in a tightly controlled fashion. Every 28 days my oncologist generates, and the insurance company approves, a prescription for Revlimid capsules, quantity 21, in 25mg strength. Eventually I am contacted by the specialty pharmacy, and I receive the same "counseling" from a pharmacist every time: I am warned against donating blood or sperm, and against engaging in sex with "a woman who is pregnant, or who could become pregnant", unless I use a condom. The pharmacist then transfers me to a patient service line at Celgene, the manufacturer of Revlimid, and I take a "survey", which is the same every time: I answer questions about whether or not I have donated blood or sperm, and whether or not I have engaged in unprotected sex with "a woman who is pregnant, or who could become pregnant". Only after I have successfully jumped through all of these flaming hoops can I be shipped the goods.

Beyond this, Revlimid carries warnings regarding, among other side effects, deep vein thrombosis (blood clots) and tumor lysis syndrome (TLS), which covers a grab bag of metabolic disturbances, the most dangerous-sounding of which is acute renal failure.

So Revlimid is a dangerous drug, maybe more dangerous even than we were thinking. Given the risks, definite and possible, should I be "allowed" to take it? In the binary world of mass media health and science reportage, drugs are either "safe" or "unsafe". No gray areas, please. No nuances allowed. And the FDA is the God of this Manichean religion, sitting in judgement over which may enter the Heaven of Safe Drugs and which are consigned to the Hell of Unsafe Drugs. For many drugs, the end of the line comes in the Phase I clinical trial. The Phase I clinical trial has nothing to do with assessing the efficacy of the drug under test. The question "Does Revlimid do anything good for multiple myeloma patients?" was not asked, let alone answered, in the Phase I clinical trial. The only objective of the Phase I clinical trial is to determine whether or not the drug is going to hurt or even kill people. Those laundry lists of "possible side effects" that come with prescription medications are generated by the Phase I clinical trials. If a patient in the non-control arm of the trial (the group of patients actually getting the drug under test, rather than the placebo) gets a nose bleed during the trial, then "nose bleed" is going to appear in the list of "possible side effects" for this drug -- whether or not the drug actually had anything to do with the nose bleed. Because, in fact, there's no way to know for sure. And if patients in the non-control arm die during the trial? Then the drug is pretty much done for. And in fact quite a few promising drugs have not survived their Phase I trials for precisely this reason. Pharmaceutical industry professionals of my acquaintance assert, with the utmost seriousness, that should it have been subjected to the FDA's approval process, aspirin would not be available in the United States today. It's simply not "safe".

And given its litany of problems, no doubt many people would be surprised to learn that the FDA has approved the use of a drug such as Revlimid for any purpose whatsoever. Probably, it is flying under the radar: few are the patients who want or need to use it, and these few are sufficiently desperate to resort to it in spite of the dangers. In all probability, they are more likely to die without it than with it. So the all-powerful FDA has allowed this, calculating that repercussions will not return to haunt it. But now it's getting nervous about it, as the safety announcement shows.

There is no way that a mass-market drug like Lipitor or Viagra would be permitted to reach the market with a rap sheet as long as Revlimid's. That sounds right, except that there are bound to be gray areas in which certain drugs could benefit a relatively large number of patients, but the FDA has ruled that out, because it doesn't want to be raked over the coals by the media and by Congressional sub-committees later, if it guesses wrong. Better to keep this stuff away from the unwashed, who don't know what they're missing anyway. The FDA is rarely made to suffer for keeping dangerous drugs out of the hands of people who might be helped by them.

Which brings us to the topic of "effectiveness", which is the subject of the later-phase trials. This is where the gray areas become very murky indeed. Technically, Revlimid is approved, in combination with dexamethasone, only for myeloma patients who have failed at least one prior therapy. I have now been prescribed the drug not once but twice in circumstances that do not fit this description: once with dexamethasone as induction therapy for a stem cell transplant; and once without dexamethasone as post-transplant maintenance therapy. When this inconvenient truth is brought to their attention, oncologists merely shrug. This kind of thing is routine, universal practice in American medicine. Once a drug has been approved for any purpose whatsoever, it will never again be approved for any other, irrespective of any subsequent research that may support such usages. Formal clinical trials done in support of an application for FDA approval are so expensive and so drawn out that no one ever does more than one set of them for a given drug, if they can avoid doing so. Physicians feel free to dispense a drug for unapproved uses if current research supports them. But they, not the FDA, make these decisions. Hence my experiences with Revlimid to date. As one of the aforementioned pharmaceutical industry professionals commented to me: "You're in the real clinical trial, right now."

The thalidomide disaster gave birth to the FDA's existing approval process for drugs. But the problem with thalidomide wasn't the absence of this approval process, the problem was a lack of adequate testing. There can be no doubt that drugs like Revlimid need to be tested and retested, early and often. What I question is the FDA's power to arbitrate what drugs can or cannot be made available as a result of these tests. Why aren't the results of drug tests simply made available to the physician community, so that they can decide whether and how to use the drugs? They are doing this job anyway, for drugs that have managed to successfully negotiate the FDA's highly politicized approval process, as my experience with Revlimid shows. To me, the FDA's control of this process appears to be less about assuring safety and efficacy than it is about control.

Sunday, March 27, 2011

Geraldine Ferraro's 12-Year Benchmark

With the death of Geraldine Ferraro, multiple myeloma claimed its most prominent American victim in recent memory -- perhaps ever. Huong asked me whether I was bothered by this. I suppose she guessed that I might consider it to be an unwelcome harbinger of some kind. Anyway, the answer is "No", and not because I'm an insensitive lout (although that could be another reason).

When Ms. Ferraro was first diagnosed, in the late 1990's, her chances of surviving five years were deemed to be slim; her chances of surviving ten years were, for all intents and purposes, nil. In the event, she managed to hopscotch past the Devil for even longer than that, on the backs of powerful new therapies that became available in the intervening years.

Short of a cure -- and curing myeloma would require the kind of breakthroughs that merit Nobel prizes -- the goal of clinical oncologists today is to render this disease as manageable as, say, Type II diabetes. The gallows humor version of this says that "success" is lodged in making the patient survive long enough to be killed by something else. That remains a goal, as Ms. Ferraro's demise makes clear, but there is every reason to believe that I will be able to live a relatively normal life for many years to come, by shifting from one therapeutic regime to another over time, following her example. Yes, I will likely have to battle undesirable side effects. There will be uncomfortable moments when Plan N is found to be no longer working, and Plan N+1 has not yet succeeded in replacing it in a stable manner. I may eventually have to resort to something previously untried. But on the whole, it would really be a little surprising, to me, if I cannot do better than Geraldine Ferraro's 12 years before I'm done, since I should have access to options not yet conceived in her time.

Wednesday, March 16, 2011


Yesterday my immune system advanced to "adolescent" status, at least in terms of childhood immunizations. I made my way to the office of my primary care doc to receive boosters for four of the five vaccines I received during my most recent visit to Johns Hopkins, in January. My primary care doc is of course not a pediatrician, but she does have patients young enough to need these boosters, so she had them on hand. I will get the last installment of these when I return to Hopkins for the last time (well, the last time related to the transplant, at least), for my 24-month checkup.

Sunday, March 13, 2011

Cancer Research: Vital To The Nation's Defense?

Apparently so, since Congress has continued to fund it via Dept. of Defense budgets for almost 20 years, and will do so again for fiscal 2011, according to this Washington Post article. Of course, this is in addition to the usual avenues of funding for such research, such as the NIH. Money quote: "Breast cancer is a 'huge issue' for women in the military." Yeah, I get it, but...

Sunday, January 30, 2011

12-Month Transplant Checkup

Wow. I knew it has been awhile since I updated this blog, but I didn't realize that it has been more than two months. That's good news though, really, because nothing exciting enough to report has occurred since then, and on this blog, excitement equates to trouble.

We traveled to Johns Hopkins on January 13 for my (somewhat overdue) 12-month transplant checkup. I have now obtained the bone marrow biopsy results, which the Hopkins oncologist describes as "awesome". The bottom line: "No evidence of myeloma".

After the tests were done, before we departed for home, I was given the first installment of my childhood immunizations. As you may recall, the transplant destroyed my existing immune system, replacing it with a brand new one more closely resembling the one I was born with. So for the past year I have been vulnerable to many diseases most adults have long since forgotten about, such as polio, diphtheria and tetanus. I received five injections, vaccinating me against the diseases just mentioned, plus hepatitis B, meningitis, and a couple of other less well known ones.

I will need boosters for all of these in March, but there should be no need to travel to Baltimore to get them; I'm guessing I will be able to get them all at Christiana. If so then I will not need to return to Hopkins until my 24-month transplant checkup, which I believe will be the last.

Meanwhile, there is just not much to say about my work experience of the past three months. It can only be described as "uneventful", which is of course blog poison. The days do drag out because of my need to take breaks, but I do not seem to be suffering much additional pain, knock wood. As for chemo brain effects, I don't see much that has happened that could be ascribed to anything like that. But maybe I have just forgotten all about it already.