Overdue update

Lots of changes in the last few weeks. I've started the next round of chemotherapy, with a new oncologist, gone on long-term disability, and finally managed to arrange a quick visit to Maryland to see Mom, Dad, and Karen. 

Dad's cognitive slippage has continued, and he needs pretty constant help. While he has trouble remembering lots of things, he is still pretty certain that he does not need to take instruction from his wife or daughter, so professional assistance is the only thing that works (my own feeble efforts are no better rewarded than Karen's or Mom's, and in any case are too infrequent to do much good). So he will be moving into assisted living soon. Mom will stay in their current apartment, which is right across the "street" (really it's a parking lot). I was happy to find a decent last-minute airfare and squeeze in a quick pre-Holiday visit, complete with a mini-Christmas dinner (glorified finger food). It wouldn't have impressed an outside observer, but our little gathering will rank right up near the top of my Christmas memories.

As for me, I am feeling good, and the new chemo routine seems a bit easier to take than previous rounds, partly because the new proteasome inhibitor (Ninlaro or ixazomib) is delivered orally rather than by injection, and especially because the dexamethasone dose is only 1/4 of the pre-transplant dose. I still go in for weekly blood draws, but am responsible for managing all the meds myself. Everything is on it's own schedule, so it's not quite trivial. Quoting from the Clinical Note: 

He will start with Ixazomib 4 mg/week (days 1, 8, 15 every 28 days), lenalidomide 25 mg daily days 1-21 every 28 days, and dexamethasone 20 mg days 1, 8, 15, and 22. Supportive care would include acyclovir 400 bid, aspirin 325 mg daily. 

The Ninlaro is something to behold. A 28-day supply consists of 3 capsules, and according to Express Scripts, they pay a little over $12,000 for those (I think this includes the negotiated discount!). Each $4000 cap comes in its own fancy (cardboard) box, although you might hope for a little gold leaf or at least some decent inlay at those prices. Of course, its true value lies in the unobservable things it does, and I don't want to sound ungrateful--I am depending on this stuff to keep me alive--but still.

Rosie is here for the week, and we have somewhat belatedly got our holiday situation together. The tree is a little on the short side. I swear we weren't (much) slower than usual in our tree shopping, but all the usual sources were mysteriously tapped out. I blame my fellow consumers for being over-eager. It's a cute tree, anyway, and Rosie was able to put the angel on top without benefit of a stool or ladder. 

2016 has been a strange year in so many ways. I guess I'm ready to take my chances on the next one. What could possibly go wrong?

Thanksgiving

We're back from a follow-up visit to Mayo, with little news to report, which is a good thing--the monsters, while still present, have not yet reawakened. I am feeling good, and have enough hair to have resumed using shampoo. That I take pleasure in this surprises me, but it is what it is. The hair is surprisingly helpful as an insulator, and I am gradually finding myself less in need of extra layers of insulation even though the temperature keeps dropping.

I'm now on long term disability, trying to figure out how to keep being useful and productive, while also trying to figure out how to balance my desire to keep being productive against my wish to enjoy as much as possible of my limited remaining time on earth.

The main point of the visit to Rochester was to plan the post-transplant "consolidation" chemotherapy.

Forgive me for getting slightly technical here, but just in case anyone else can ever use the information, I do want to record the plan we arrived at and the reasoning. A consistent theme from clinical trials is that patients like me with 17p deletions respond better to the class of drugs called proteasome inhibitors (Velcade, Kyprolis, Ninlaro) than to other classes of  drugs used to treat myeloma. So we want one of those, along with dexamethasone, which is both dirt cheap and the best single drug for knocking down the category of cells (lymphocytes) from which the tumors originate. The effect is much broader than you might hope for, and the side effects are unpleasant, but umpteen clinical trials have shown dexamethasone to be better than any known alternative. The last drug in the regimen is called lenolinamide, which goes by the brand name Revlimid. It's a close relative of thalidomide, the drug that got famous for causing horrific birth defects in the 1950s. Its action as an anticancer agent is not totally clear, but it has a great track record in myeloma, and has been responsible for a major improvement in survival. However, it's not as clear that it works well for patients like me.

Last year, a handful of new myeloma drugs were approved by the FDA. Among them were one proteasome inhibitor (Ninlaro), and two monoclonal antibodies (Darzalex and Empliciti). Because they're newly approved, and patented, and this is the U.S.A., they are all wildly expensive. Revlimid, Kyprolis, and Velcade are also wildly expensive, by which I mean a year's supply of any of those drugs will run between $100,000 and $300,000 per year, if your insurance company won't cover them.

And there's one more consideration. Revlimid and dexamethasone are tablets. All you have to do is swallow them. Almost all the rest are delivered by infusion, which means that you go to your local hematology/oncology clinic and hang out for an hour or two while an IV is delivered into the increasingly less willing veins in one or the other arm. If you've had any recent contact with your local health care providers, you will realize that "an hour or two" in the infusion room means a minimum of three hours of real time. Velcade can be delivered by subutaneous injection, which takes less time, but still requires showing up for an hour or two, and leaves ugly red welts all over your belly.

Darzalex may well be a wonder drug, and I definitely expect to make use of it. But it is not a cure, so it makes sense to put off its use until what I'm doing doesn't work anymore. Meanwhile, Ninlaro is a proteasome inhibitor, to which I'm likely to respond well, but I can take it orally, so I will not be tied to an infusion center for hours on end. So we're going with Ninlaro/Revlimid/dexamethasone. It's not a cure, but then again nothing is. And we'll probably need to change it out after a year or so.

Apologies to all for whom that was too much. May we all survive the next four years.

Benchmarks

There hasn't been much to report since we've returned to Louisville, and I have dutifully failed to report. Liz and I have been taking care of business old and new, between filing insurance claims, re-establishing our relationship with the US Postal Service, obsessively checking presidential poll aggregators, and so forth.

The weather has been spectacularly good here, and I became strangely obsessed with rehabbing some outdoor furniture we brought here from Salt Lake that had been sadly ignored. It got a few days of attention, and looks a little better, anyway. I've been working on the bike and feeling better, although I do need to lie down for a while after a ride.

And there has been baseball. I grew up a Phillies fan (it used to be a congenital condition, as no one with any sense would adopt them as a favorite), back when they were still working off the 77 year-long interval before winning their first World Series. When I was in grad school, living in Chicago, it was fun to play hooky on the occasional summer afternoon and take the el down to Wrigley. This was a few years before they put lights in, so all the games were afternoon games. The bleacher seats were $2, the beer was cheaper than that, and a few of my heroes from the 1980 Phillies had been traded to the Cubs. I'll spare you any further details, but it was easy to fall in love with Cubs, especially in 1984. Never mind what happened then. Or that other thing.

So I do have to say: Cubs win! Cubs win! And attribute it to Jack Brickhouse, although it may go back further. He was gone by '84, but a bit easier to take than Harry Caray while I was trying to comprehend the finer points of principal components analysis.

I'm thinking that I will make it a goal to be alive for the next time the Cubs win the World Series. On second thought, that might be setting the bar a little low, since those guys could do again next year. Maybe the Phillies, then. That's definitely a reach.

Wrap Up

Today was the exit interview, where we talked about the schedule going forward, and interpretation of the latest numbers for assessing how well I responded to treatment. The plan is to begin maintenance/consolidation chemotherapy, similar to the induction chemo I was doing pre-transplant, at about day 60, which will be mid-November. Also at that time I will start on my "childhood" immunizations, which I need because my immune system has undergone what amounts to a "factory reset."

In terms of how I am doing right now, I basically sailed through both transplants without a single really bad day. I'm grateful for that, but am more focused on what's left of the disease at this point. The truth is it's a little hard to say--which is a good thing.

The disease is caused by proliferation of a single lineage of plasma cells. Plasma cells are responsible for making components of antibodies--each lineage just makes one part of the molecule--so you can assess how much disease there is by looking at the ratio of the component that the tumor cells are making to the other (normal) components. When people are first diagnosed with myeloma, the ratio is often 100 to 1 or higher. After treatment, a ratio of 1.0 should mean no measurable disease. Some people actually achieve this, although I haven't yet. One problem with ratios is that when the numbers are small, ratios are unreliable--so measuring how much disease is left gets harder as the amount of disease goes down.

Responses to treatment for myeloma get translated into a set of categories: complete response, very good partial response, partial response, stable disease, progressive disease. They're fairly broad categories, but they are clinically useful. My response, right now, would be classified as "partial response," falling just shy of a "very good partial response." I think of it as "pretty good partial response" although obviously that's not an official category. So the target for post-transplant chemo is going to be that small amount of residual disease, and the new drugs that are available make that seem like a reasonable hope.

Home Stretch

I've been owing a post for a few days now. There's a lot to report, but here are the headlines:

1. The possible infection was real. It turned out that the knee was fine, but the inspection of the central line revealed a couple of tender spots that led to cultures being taken from both tubes and a separate culture from my blood (straight from a vein, no tubes). The first two cultures were positive, but the last was not, meaning that the central line itself was the reservoir of the infection and it had not spread to my blood. So I've been on twice-a-day infusions of vancomycin all week, and yesterday they decided to pull the central line. That's a great relief to me, and everything feels better already. The downside is that all the rest of my blood draws and infusions will require sticking a needle in a vein. Believe me, I am totally accustomed to that, so it's no big deal.

2. The other news is all good. I have more than enough platelets and leukocytes to go home, and have an exit interview scheduled for Tuesday. The erythrocytes look like they are starting to come back a little now, as well. So we should be pulling out either Tuesday or Wednesday.

Next up: an assessment of how well I've responded to the transplant, and considerations about where we go from here.

+11

Last time around, day 11 was the day my hair started coming out. What hair I've still got is hanging on today, but I don't think it's all going to survive the next few days--unless it's more a question of selection than attrition. We shall see. Visually it won't make much difference, since my current crop is short, sparse, and predominately white.

The white cell (leukocyte) counts rebounded quickly from the nadir (<100, 200, 200, 500, 700, 800 million/L on successive days), a couple of days ahead of last time, and after a deeper drop the platelet count has gone up on its own since yesterday (5, 13, 18 billion/L, though the 13 was aided by a transfusion on Sunday). So I am already over the line for leukocytes, and probably have only another two or three days before the platelets are at acceptable levels.

The red cells, as before, are lagging, and today I posted a lower hemoglobin (9 g/dL) than ever before. As long as this number doesn't drop much further, a little anemia won't keep me from being released. The new thing this week has been a little scare about infections (the coffee table bruise took on some extra redness that concerned the docs), so I have been doing two a day infusions of vancomycin while we wait for the blood cultures to come back. I am convinced there is no infection and that the bruising was just weird because of the combination of no platelets and a vintage de Sade coffee table. Also my clumsiness. As a bonus, though, I got to watch most of the presidential debate hooked up to an IV drip, which provides a feeling of distance. If we'd only thought to watch with the sound off it would have been perfect.

We deliver for you

Day +7, platelets crashed, and had a bag of platelets transfused. Just in time, too, since I had just crashed my knee into the coffee table. Almost immediately the knee swelled alarmingly, so we had a reminder of why platelets are a good idea.

How I came to crash into the coffee table might be a better story--I was distributing the mail, which contained an amazing item.

Rosie moved to Boston this summer, bringing with her a car that had outlived its usefulness. After casting around a bit, we determined that we were going to donate it to the International Myeloma Foundation. This turned out to be difficult, because she didn't have the car's title (I did). So I tried to send it to her, but apparently messed it up in some way that may it non-transferable.

When we were home for a few days at the beginning of August, I went to get a replacement, but the new title had to be mailed from Frankfort. We'd had no problems (other than that it costs $15/week) with the USPS' "Premium Forwarding Service" on our first foray to Rochester, so I set it up for our trip to Colorado. The idea is that once a week the post office bundles up all your mail and sends it to you in a single package. When we got to Colorado, we went to the post office every day or two, but nothing ever showed up. We talked to the clerk, who took my phone number and was trying to be helpful, but apparently "Premium" does not include a ready way to track packages. We returned to Louisville with no mail.

So I visited our Louisville post office, took phone numbers, gave them mine, all to no avail. Apparently this was all the responsibility of someone named "Norm" (really!), who was on vacation until Monday or maybe the next Monday. Sadly, we had to get back to Rochester, to yet another address, before Norm was due back. The PO people advised me to skip the Premium Forwarding Service and go with regular old forwarding. Meanwhile, our mail has been AWOL for almost a month.

Back in Rochester, we began with phone calls. First to Colorado, where the same clerk was still helpful but still hadn't seen the mail. Then to Louisville, where Norm remained on vacation, apparently. No joy at all. An hour later my phone rang and the clerk from Colorado(!) had apparently called the Louisville post office and shook them down for a tracking number, which she gave me, along with the news that the "To" address that the USPS had in their system was not our current address, nor the Colorado address, nor our home address, but the first Rochester address we were using in July. So the package was at the Rochester PO, marked "Undeliverable as addressed."

I headed over to the Rochester PO, and spent an hour waiting for someone to search the apparently unordered heaps of undeliverable mail, only to report that she could not find anything matching this tracking number. She thought it might have been out for delivery, in the possession of the carrier. Two days later, we tried again, and during the course of a lengthy conversation, I found that I could at least set up alerts so that any time the package status changed, I would get an email. After we returned empty-handed from the PO, I got a new message: 3 hours earlier, the package had been returned to Louisville.

I waited two days and called Louisville, asked for Norm. I didn't get him, but the woman I talked to left a message. An hour later, Norm called. I hadn't actually believed that he was real. But he was, and claimed to have our package right in front of him. He promised to send all our outstanding mail in a single package to our current address. Two days later, that package arrived. It contained shipments made during the entire time we were in Colorado, not a single piece of which was necessary or important. And no title.

So today, about a week later, what should show up in the small trickle of yellow-labeled forwarded mail (mostly these are bills from Mayo) but a nice clean new-looking envelope from the Kentucky Transportation Cabinet, containing a title issued August 8. What happened in the interim is anyone's guess. By happy coincidence, Rosie is here visiting us right now, so I was happily (perhaps too happily) delivering the title to Rosie when I hit the coffee table.

nadir, round 2

Today (+6) the leukocytes dropped to near 0, with platelets not far behind. So we'll be here for a few days, maximally isolated. I'm feeling OK, definitely sluggish. Still no major nausea, diarrhea, vomiting, though, and looking forward to the climb back.

Rosie arrived yesterday for a few days' visit. I'm not very lively company, but it's always great for both Liz and me to have some new conversations about new subjects, and since Rosie has just started a new job (her first real full-time one) in a new city (Boston) she has lots to report.

Bizarre torrential rains the past few days, but we stay mostly indoors and dry.

downslope

The cell counts are going down now, though I'm still feeling OK. I'd guess I might get to the nadir Wednesday or Thursday. The general feeling is that digestion and metabolism are just sluggish, and everything takes longer to happen. No major drama.

Today's events were enlivened, if that's the word, by a morning visit to the podiatrist. This was scheduled back in July, when my right leg and foot were seriously uncomfortable with some combination of muscle strain and nerve damage. Right now, my leg feels fine, although there is a spot in my right foot that's bothered me for many years--the neurologist thought it was a neuroma, and the podiatrist (who, this being Mayo, was really and orthopedic surgeon) was supposed to consult. I'd meant to reschedule or cancel, but hadn't remembered to do so. It wasn't like I was going to schedule foot surgery with all this other stuff going on.

The appointment took about an hour, and consisted of some of the most excruciating time I have spent here, including the ring extraction. Both the resident and attending docs, but especially the latter, squeezed that foot (and the other one, for comparison) in about 100 spots, almost all of them affirmative in response to the question "does it hurt when I do this?" If I had any ticking bomb secrets to tell, I would have spilled them in the first few seconds.

The conclusion: my feet are all messed up, and maybe there's a neuroma.

Day 0 times 2

Wednesday was the high-dose chemo, yesterday the transplant, and everything is waiting now. I'm feeling fine, the one noticeable difference the increased fumes from the cell preservative (DMSO) which leave a funny taste in my mouth and apparently fill the room with a "creamed corn" smell. Apparently, the longer freezing time for this batch of stem cells increases this effect. Black coffee tastes good, though.

It's time to starting saying goodbye to the first batch of stem cells, shock troops for the tandem transplant, holding the fort while being mowed down by "friendly fire." Sorry for the war metaphor--it's obviously overdone and maybe I've said before that a cancer patient is more the battlefield than the warrior. Anyway, the theory of the thing does still bug me, but I finally found these results that both Drs. Dispenzieri and Gertz had mentioned, and they are encouraging:

Source: Cavo M, Salwender H, Rosinol L, et al. Double Vs Single Autologous Stem Cell Transplantation After Bortezomib-Based Induction Regimens For Multiple Myeloma: An Integrated Analysis Of Patient-Level Data From Phase European III Studies. Blood. 2013;122(21).

OS means overall survival, hr-cyto means high-risk cytogenetics (like mine), and failing CR means not achieving a complete response after the first (induction) chemo treatments (also like me). So this graph shows combined data from a number of European studies for patients with characteristics just like mine, who were given either single or double transplants (abbreviated above as ASCT). After 4 years, the differences in survival between the two groups are huge, and the relative risk of dying (the hazard rate, HR) across the whole period is much lower for the patients who received tandem transplants. This is about as good as it gets in clinical studies. So never mind the theory, it looks like something important is worth doing. 

The plan for round 2

Today we met with the transplant doc, NP, and clinic coordinator to go over the procedure for the second transplant. Nothing new here for us, but here's a quick review for those watching from home: tomorrow I'll get a central line (aka Hickman catheter) installed, through which the chemo, stem cells, and all the many blood tests ahead will be routed. Wednesday they will give me the main chemo drug, melphalan, and a couple of others to minimize the immediate side effects. Thursday is a day off, then Friday is the transplant. After that, we try to stay out of trouble and wait for everything to work its magic, with daily monitoring of cell counts, vital signs, fevers, nausea, vomiting, etc. The whole experience should be a little more streamlined because we do not have to collect a new set of stem cells--we just use one of the two remaining bags that are in the freezer.

Past performance is no guarantee, but I am hoping this time will not be too bad, either. We hope to be done by the end of the month.

Back for more

We're back in Rochester for the second transplant. Yesterday was biopsy day, which in principle should say something definite about my response to the first transplant, but it's hard to parse the results posted so far, except to say that it's clear that there still are tumor cells actively reproducing, and that they generally look pretty similar to what was there before the first transplant. This is not surprising, although many people do better. That's why we're back. Such is the state of the art in oncology: do the same thing over again and hope for a different result. Sometimes it works, too.

Before we left Louisville, I did manage to get in a bike ride--nine miles with no trouble getting up the same hills that nearly did me in at the beginning of August. I was pretty sure that the red blood cells had come back, and yesterday's blood work confirmed that they had more or less returned to normal values. Too bad they won't be sticking around for long. I was just beginning to enjoy the feeling.

Chilling

Chilling is not a word I'd ordinarily use, except maybe ironically, to describe what I've been doing, since it seems to belong to another demographic entirely. I'm making an exception here because it is also literally true. It has been cool and damp here in SW Colorado, where we have been holed up for a few weeks.

I realize (after several concerned inquiries) that the extended silence following a post about having trouble breathing was poor form, and I apologize for leaving people hanging. I am pleased to report that a steady diet of thin air and good food has been helpful, and my stamina has increased markedly since we have been here. Polly and Barrett have been great hosts and wonderful company as always, and Sancho the dog became slightly unhinged by my willingness to play fetch with him for hours on end. Two days ago Barrett and I climbed West Baldy, which at 9780 feet is by no means monumental by local standards, but has always been a good workout for me.

Here are a few pictures. The first one is relevant to chilling, as the snow-covered ridge in the picture was about 1000 feet below us when I took the picture. It must have resulted from a tiny temperature inversion, although it was plenty cold above, too.

Snow at -1000 ft.

Barrett checking on the neighbors.

West baldy.

Heading back home Friday, with a quick turnaround to Mayo for Round two.

Bike Rides

So we're back in Louisville for a few days. One of the consequences of being released from the daily clinic visits is that I no longer have a daily readout of the various cell counts. The white cells and platelets were doing just fine last we heard, but the red cells were still lagging.

A couple of days ago, I grabbed my road bike and set out to see how that felt. I looped around the neighborhood for a mile or two, then headed for Seneca Park, which is reached by a very short (0.1) mile climb with a fairly steep (9%) grade. When I got to the top, I nearly collapsed, and had to lean carefully on the bike to keep from falling over while catching my breath. After I'd recovered, I reconsidered my ambition level, made another short loop in the park, and returned home, with one more hill climb of similar dimension, and similar result. I had honestly never had to stop to catch my breath after climbing a hill in Kentucky, and here I was totally destroyed by two hills that had barely registered in my consciousness in eight years of riding. So that's an indication that the erythrocytes still need some time to recover.

Today I scaled back my ambition, using the mountain bike to remind myself that I was not intending to go fast, and managed a few loops without having to stop for oxygen supplementation. Most of today's progress is probably the result of changing my behavior, rather than actual recovery, but at least there's some semblance of balance between my expectations and reality (for now).

Let's Play Two

On balance, given what's currently known, we've decided to go for the second transplant. It's certainly not guaranteed that I will tolerate the procedure as well the second time, nor is it guaranteed to "work," but there is at least a lot of evidence that tandem transplants have worked for many people in my situation, and when the second transplant is finished, all options for using some of the exciting new drugs on the market will still be open. A couple of interesting clinical trials that are currently underway will probably report results this Fall, which may lead to some new drug approvals as well.

So we're looking at returning to Rochester around the second week of September (~ day +60), and probably finishing up around October 1 (it should take a little less time, because the stem cells are already collected).

Might be a few quiet weeks on the blog, but I plan to report on transplant #2 as it happens, if anyone is still following by then.

But wait, there's more . . .

A long day, starting with the usual blood draw, followed by a session of inhaling pentamidine (an antibiotic that should give me 30 days of protection against pneumocystis pneumonia), exit interviews with transplant nurse/coordinator and hematologist, and finally the removal of the Hickman catheter (aka the central line).

It turns out I'm not too good at this inhaling business. They positioned me in front of a hood (above which was a TV with some Discovery Channel show about surviving in Alaska) and handed me a plastic mouthpiece with small clouds of vapor pouring out, I was to stick this in my mouth and "breath normally." As soon as someone tells me to breathe normally, I have no idea how to breathe. Nose? Mouth? OK definitely not mouth. Nose is ok. Don't hyperventilate. Deep breaths. No, regular breaths. By this time and for the next 15 minutes I am totally lightheaded and never did feel right for the rest of the day. Meanwhile, the Alaskans had to kill their old milk cow in order to get enough meat to survive the winter.

The exit interviews started smoothly enough, with the nurse/coordinator giving us instructions that apply to most of the transplant patients. After a while, I remembered that the schedule was going to be different in the case of tandem transplants, although we hadn't decided yet whether to go that route. So that confused things.

Tandem transplants (in other words, two planned transplants within a short period of time) are kind of a weird idea.

Consider the basic transplant: first, you harvest a bunch of stem cells and freeze them. Next, you kill off the remaining stem cells in the marrow with melphalan. Next, you put the stem cells back in, and wait for them to grow. They grow, and you go home.

But a tandem transplant means that you give those cells a few weeks to multiply happily, and them you kill them. And do it over again exactly the way, except using a bag of stem cells that's been frozen for a couple of months.

So how could that be better? It turns out that the melphalan doesn't kill all the stem cells. Labeling studies seem to show that recurrent disease doesn't come from the transplanted cells, but from cells that survived the chemo. So the second transplant cleans up after the first, and the first batch of stem cells is sacrificed for the purpose. That's the theory. Personally, I'm trying not to feel too much loyalty to that first bag of cells.

The next piece of complexity is that the clinical trials that established that tandem transplants work better than single ones for people with disease like mine are getting a little old, many of the drugs have changed, and a lot of new drugs have come on the scene lately that seem very promising. So it's difficult to decide what to do next.

Working on it. Stay tuned.

If you sit around long enough, something will happen

Today was a slow day for me. Tomorrow we have exit interviews, removal of the central line, and an inhaled antibiotic (pentamidine, to prevent pneumocystis infection). So that will be plenty, but today was a little bigger for Liz than for me.

Liz wisely had taken advantage of all the down time to get a skin survey from the dermatology clinic, and sure enough they found a basal cell carcinoma (that's the most common and least dangerous kind of skin cancer) just around the corner from her right eye.

Even though a BCC won't kill you it can be very inconvenient to remove, and this one put up some fight. She's got a lot of stitches and the swelling to go with it.  Now we can really scare the children when we walk down the street together, me with my shiny skull and black face mask, and Liz with her eye not-quite-a-patch. Before they started surgery, a professional photographer came in with a big SLR and reflectors to take what are no doubt exquisitely detailed images of Liz's tumor. There was a minor epiphany when we realized that this was exactly the source of those horrible photos that grace every dermatology textbook, though in fairness Liz's BCC was not nearly horrible enough to make it big. She did sign a release, though.

All over but the shouting

Today's numbers are well over the threshold required for release: 1 billion neutrophils/liter, 109 billion platelets/liter. So the next step is to schedule an exit interview with the hematologist and get our walking papers. There are a lot of details to work out, especially whether to do second transplant, but also more mundane things like scheduling blood draws and interim treatments.

I'm hoping we get to meet with the hematologist tomorrow, but it might be Friday or Monday. It will be nice to move on, although this will not be the end, one way or the other.

Over the line

Today the platelets hit 77 billion/liter, and the neutrophils hit 700 million/liter, both good enough to get me released after a few more formalities. Neither of these values is within the range considered "normal" yet, and the hemoglobin still has to come up from 9.9 grams/deciliter to something more like 13-14 before I will really have recovered the fundamentals; moreover, my understanding is that my new immune system will take a while longer to really be fully functional.

Also, the successful completion (or really near-completion) of the transplant is in no sense a cure. The myeloma is still there, greatly weakened (we hope), but impossible to eradicate with any tools we now have. In the next couple of days, we'll have some data on how deep the response to treatment has been (basically how many, if any, of the tumor cells are detectable). That should help us work through the next steps.

Daylight

Just a short note today--all good news. The escape criteria for me are: absolute neutrophil count > 500 million/L, and platelets > 75 billion/L one week after the last transfusion. I'm not there yet, but closing in: neutrophils are 450 million (up from 220 million yesterday), and platelets are at 47 billion, up from 28 billion yesterday. Another day or two should probably be enough. The red cells, hemoglobin, etc., are still lagging, but they never fully dropped into the danger zone in the first place.

Upslope

Day +13, and my hair hasn't grown back yet. But seriously, the blood cell lineages are all coming back now. Platelets are now giving the leukocytes a good run for their money, with the erythrocytes hanging well back, although the hemoglobin numbers are good enough that I shouldn't need any additional transfusions. Also I feel much better. I think it will only be a few more days before the blood numbers are up in the range where we can start talking about heading out. That's probably overly optimistic, but we shall see.

I've been reading up a bit on the tandem transplant idea, which has some puzzling features, and will post about that after we've grilled the senior docs at greater length.

Liz's sister Polly is in for a few days, which has me thinking about getting out West ASAP.

"Supermoon eclipse" rise, Sept 2015. 

Hair

Day +12, and the hair is definitely on the way out. Basically I hadn't lost any hair until yesterday, when it started coming out rapidly (not in clumps--more like a shedding dog but a lot faster). It's making a big mess, so there's nothing for it but to call in the clippers.

The beard is putting up more resistance, so we'll see. Anyway, I'm thinking that if I just got myself a black turtleneck I could go to Silicon Valley and raise a billion dollars for . . . something.

As for the other, actually important, stuff: it's all good. Platelets have just started coming back, white cells continue to rise, hemoglobin is hanging in there, and I feel better each day.

The Climb

Today the leukocyte (white cell) count was 0.4 billion/liter, neatly overturning my hopeful hypothesis that cells were more than doubling every 24 hours. Let's see . . . 0.1, 0.2, 0.4 . . . hard to argue it's not doubling. Well there's no need to be greedy--at this rate I could get back within the normal range in a few days. Also good news was a meaningful uptick in erythrocytes (red cells) and hemoglobin, so I most likely won't need any further transfusions. It's hard to call the platelets, since my last transfusion muddies the water. But the news is good.

There are consequences, though. Last night I was slightly feverish (~ 100), and felt generally lousy. This morning (day +11), my hair officially started falling out. It's not clear how much I'll end up losing, but it was as though a switch was thrown. I will probably have the nurses give me a buzz cut tomorrow (pictures to follow), on the theory that losing a lot of small hairs will be less obnoxious than losing longer hairs. We'll see. So far, for better or worse, the beard seems to be hanging on.

0.2!

Today is brutally hot, demonstrating that Minnesota can almost hold its own with Kentucky for summer unpleasantness (although far less often, and less severely, to be fair). It's another good day to lie low, which suits our lack of options.

For whatever reason the transplant ward (aka Station 9-4) is really busy this week, so when we came in this morning no rooms (or half-rooms) were available. After a few minutes we were shown to the window side of one of the rooms, with another post-transplant patient nearer the door. The nature of these rooms does not allow for privacy in any real sense, and since she was there first all her visitors and conversations were totally audible to us.

I only mention this because it is a small and rare (for us) insight into an alternative trajectory of post-transplant recovery--she had lost her hair, was having severe diarrhea, was being screened for a wide range of gram-negative and -positive bacteria, and generally feeling miserable. However, her cells were engrafting, and she was ahead of me in terms of bone marrow recovery.

For me, today is +10, so I am waiting for hair loss. Not much to report on that front, yet. The nutritionist did not apparently need to see me today because I have been eating too well (I was looking forward to reporting the gyro and fries I'd had for lunch yesterday). No new symptoms to report to the nurse or PA, so we had an extended discussion of Liz's and my competing hypotheses about why my right leg has resumed hurting: Liz says that the diagnostic workup (involving electrial stimulation via fine needles stuck into nerves) may have had a therapeutic effect for a few days, while my hypothesis is that the immune system had gone quiet (hence no inflammation) but is now coming back. My hypothesis serves double duty as wishful thinking, of course, while Liz's suggests that people should stick my legs full of holes at some future point. In fairness, the one time I tried acupuncture it was completely painless and involved no electricity.

The blood numbers had started to come in when we got back home, and the red cells and platelets have not changed (except for the addition of bag of platelets I got yesterday). I might need red cells by tomorrow, depending. But there was good news after all: white cells went from 0.1  billion per liter (lowest possible reading) to 0.2 billion per liter, the first meaningful uptick. Given that the unknown minimum count is probably well below 0.1 (the docs say 0, but we won't ever really know), 0.2 means they have probably doubled several times already between the nadir and now.

So tomorrow I'm expecting to see more white cells (they need to keep doubling a few more times before they get to anything close to "normal" ~ 3.5 billion/liter), and hoping the platelets and red cells will join the party soon.

Platelets

Day +9. Not much going on yet. The erythrocytes (red) and leukocytes (white) are still scraping along the bottom. Today the platelet count dropped enough that they called me in this afternoon for a transfusion (that's the first one, which is pretty good for this far into the transplant). Back in the day, I used to be a regular platelet donor, so I kind of have a positive bank balance, for what it's worth. The platelets look kind of yellowish in the bag, and are delivered, slowly, with the usual saline drip. It takes about 2 hours altogether, and I managed a decent nap. For me, at least, I felt fine before and after the transfusion, and noticed no difference whatsoever. Of course, I am trying not to bruise or cut myself (succeeding so far, knock wood).

The weather here is brutally hot right now. Not much for it but to lie low until things improve.

Flatland

Yesterday saw the first rise in any of my blood counts. The red cells had gone from 3.29 (trillion/liter) to 3.32. Now I am more resistant than most people to the overinterpretation of small differences in the presence of unknown (but presumably substantial) amounts of measurement error, but still, it made a nice little graph:


Notice the little up-tick on the end. Another thing that happened yesterday is that my right leg started feeling more like its old self (not back when I had no complaints, but the more recent old self when I did . . .), in other words, it started hurting. Which was maybe (probably) an increase in inflammation, which might have suggested some immune system involvement. So maybe my white cells were starting to engraft as well, even though the leukocyte count was still pegged at 0.1 and platelets were cratering.

This morning I felt better than I had in at least a week, and was ready to go post some blood numbers.

So maybe tomorrow. It turns out that the red cells are probably just bouncing along the bottom, and the rest of it is maybe just wishful thinking:


[My apologies for the quality of these graphs, although I hope they make the point. It would be embarassing to admit how long it took to get them here at all.]

In any case, I really am feeling better (other than the leg, but screw the leg) I'm going to read up on the process of engraftment. If I learn anything interesting and not overly technical, I'll post it later on.

Nadir

Apparently it is pronounced like Ralph's last name. I always imagined something slightly more exotic, nah-deer. But anyway, we are here. That's no surprise, really, after yesterday's numbers, but it adds maybe a little bit of technical drama, at least for us numbers guys. It will probably be several days before any signs of recovery start, and with luck I will continue to feel pretty good through it all--as I do.

We saw Nell off today with a stop at a Greek breakfast place, where I managed to consume a full spanakopita omelet with hash browns, toast, and a tall tomato juice--all while watching what seemed to be Rochester's version of Pride Fest unfolding in front of our sidewalk table. It was a very pleasant, breezy morning, although it's pretty steamy now and I guess for the rest of the week. Too bad, but this is a week to lie low anyway.

I asked the nurse today when I could expect my hair to fall out. She said "Day +10" with a perfectly straight face (she is one of the more serious nurses), although she waffled a bit under cross-examination. Seems strangely late, but it will be another source of intrigue to see how she did. Maybe I can get the nurses to do a pool. For the record, it's Day +6.

The Valley

Today I woke up feeling pretty good. No nausea, not much leg pain, a tiny headache that coffee is still allowed to cure. Apart from the fact that I had woken up an hour earlier than I thought--because my phone was dead and the next device I consulted was still on eastern time--things seemed pretty manageable. I had coffee, cereal, listened to NPR, almost a normal morning.

At the clinic they drew my blood and did my vitals as usual, and we chatted with the nurse about how good I was feeling. After a while, I saw that the lab numbers were starting to come in on the Mayo phone app (the automated values are visible to patients in real time). Shortly after, the PA came in for our morning consult. First he noted that the MRI results from yesterday showed some narrowing of the small hole that one of my leg nerves passes through--but it was on the left side, not the right. Then he pointed out that my white cell count was down to 0.3 (billion) per liter, so we were nearing the nadir (that's the official term), which is fixed at 0.1 (billion) per liter, apparently because that's the lower limit of reliable detection (seems a little high to me, but I believed in Theranos, so what do I know). Anyway it was 1.7 (B/l) yesterday, so it did drop like a stone. I still felt good, but it took the wind out of my sails a bit.

In fact, this is what we want, for the existing blood cell lineages (pre-transplant) to crash. The resurrection takes place after that. But this will be the critical period for avoiding infection (yes I do hate the mask, but most of the rest is pretty easy to work with). Also maximum fatigue (red cell loss) and bleeding risk (platelets).

The good news is that I really do still feel pretty good, numbers notwithstanding. I hope this foretells rapid engraftment (that's the process by which the transplanted stem cells take up residence in the marrow and start pumping out the various blood cell lineages).

I don't always look my best, though.

I am smiling, really.

+2, +3

Yesterday was given over to a side issue. For a few weeks, I had been bothered by pain in my right leg that kept me from sleeping for extended periods. We mentioned that to our nurses at some point, and they scheduled a neurological consult.

So I got to walk on toes and heels and push against resistance in any number of directions, and it seems that my right leg had some obvious deficits. No need to get into all the details, but as I understand it: 1) some of the pain might come from incomplete healing of my 2007 knee repair (it was a hamstring graft and maybe the hamstring didn't heal right; 2) some nerve is pinched (details on which, where, and why presumably to follow); and 3) a neuroma in my right foot, just for fun.

This was all followed by a highly enjoyable session of having a resident stick electrified needles in various nerves in my leg (up to the sacrum) and inscrutably mapping the electrical signals being transmitted. He assured me that they all learn on each other, so he knew what it felt like, which was a small comfort.

If any of this is going to get fixed, it's going to wait until after all the fun and games are over, but it has a delicate relationship to my current situation. For a few days post-melphalan leg pain wasn't a problem because I had been given a fair dose of dexamethasone, to counter inflammation from the chemo, and that had been more than up to the task of making me forget about the leg pain. When the dex wore off, the pain came back, and my previous "solution" (tylenol PM) is forbidden by the transplant people because they don't want me using any medication that will mask a fever, which could be an indication that I need to be hospitalized for neutropenia. Ibuprofen, and other NSAIDS, are out because of the fever issue and their potential to damage kidneys. So that leaves opioids. I have a prescription for oxycodone, but I have been reluctant to start on it, not from fear of addiction, but because I have been seriously constipated, and my few brief encounters with oxycodone had ended with me choosing pain over constipation.

Meanwhile we had received a wide spectrum of advice from nurses, NPs, residents, and attendings. As a rule, the more senior the personnel, the more reluctant they were to advise stool softeners or laxative, on the theory that in a few days everything was going to be plenty loose. We ended up with stool softeners and, ultimately, a laxative. The good news is that it worked, and now that the constipation is under control, I may have some options for keeping the leg pain under wraps for a while.

So I got a good night's sleep. When I woke up, I had the first bout of wanting-to-throw-up that I've experienced thus far. It didn't amount to anything, but it's maybe a sign of things to come.

Day +1, +2

Every day, we go into the clinic to get blood drawn and a basic checkup.

We've been warned, of course, about the coming flood. Diarrhea, nausea, vomiting, but right now they're sure isn't any action. Anywhere. My chief complaint is constipation. My blood counts are OK, white cells hanging in there for a bit longer, reds declining but not to the level of anemia, platelets in between.

Yesterday we went to a lovely park in the area, and walked. It did nothing for my gut, but it was a nice walk on a beautiful day, so that is nothing to sneeze at. Yes I know my selfie technique needs work.

I don't feel great, but mostly I'm just really grumpy right now.

Liz's sister Nell will be visiting for a few days starting tonight. It's great to have people come so that we don't go stir crazy in the little apartment. We're pretty boring company at present. 

Day Zero

Day Zero is the day the collected stem cells are returned, a new birthday for my bone marrow and all the blood cells that are made there. For me, that day was today. We started at 5:15 AM (these hours!), and finished at 3:00 PM or so. On the surface, it is a pretty restful day, in which I lie in bed (and Liz has a reasonably comfy recliner) and have fluids dripped or pumped into the central line. The only interruptions being frequent trips to the bathroom because of the high volume of fluids. The nurses treat the cells gently, thawing in a water bath and using gravity to feed them into the line, which runs slightly pink because a small percentage of the specimen consists of red blood cells that do not survive the freeze-thaw process. The stem cells survive in part because a preservative called dimethyl sulfoxide (DMSO) is used that buffers the cells from the rigors of freezing and thawing.

Besides the cells and massive doses of saline, I'm given tylenol, benadryl, and cortisone to prevent any short term allergy-type reactions (mostly, it seems, to the DMSO). We are also told that the DMSO, presumably because of its sulfur content, can produce bad smells and tastes that come right out of me, but are noticeable and unpleasant for those around me, too. Combined with the deodorant ban, this could be a difficult period, although minor in comparison to the nausea, vomiting, and diarrhea that I'm promised.

So far, none of this has come to pass. Mostly I'm just tired, as my red blood cell counts drop toward anemia, and at the same time the engraftment process will start to make use of the suddenly-depleted energy-delivery mechanism.

Consolidated

Today was the step called "consolidation," for reasons that are unclear to me. It could be called "the day they give you an IV full of a mustard gas derivative in order to kill your bone marrow" but that would probably not be good for business. In any case, I have been served.

There are four different anti-nausea drugs, two antibiotics, one antiviral, and one antifungal. Apparently the nurses offer barbering services to make the hair loss less messy.

It takes a while for the Melphalan to work its magic, so at present I feel OK. I have a whole new set of rules from now on, including:

1) no toothbrush: I have little sponges-on-sticks, and I am to "brush" with saline.
2) no razor: electric only (yes, I do [did] shave)
3) no nail clippers
4) no deodorant, or anything scented
5) no walking barefoot, even indoors (also no shoes in the house, which makes it complicated)

As far as I know, I am still permitted to eat with a fork. This may be an oversight resulting from the fact that so many people seem to lose their appetite completely. Hasn't happened yet, I can report.

Tomorrow is a day off with just a quick check of blood counts, and Monday is transplant day (5:00 AM).

That's a lot to swallow (not including pain and nausea meds "as needed").

The Ring

Prior to heading down for anesthesia, I was instructed to remove all "jewelry," which for me consisted of my orange Multiple Myeloma Research Foundation wristband, my fitbit, and my wedding ring. The first two items came off without a hitch, of course, but the third has been a part of my left hand for thirty years and was not interested in finding a new home. Using cold water and soap, I failed to remove it. The nurse gave it a try with Windex, but did no better. It was concluded that the ring could stay.

Down in Anesthesia, however, this decision was revisited. The surgeon explained that electric cauterization would be applied to the surgical incision, and the current would pass through my body, mostly to a large grounding pad on my right thigh. But he couldn't guarantee that some current would not heat up the ring enough to cause a burn. One of the more senior nurses was called over for a consult--she was good with rings. I soaked my fingers in ice water for a minute or so, and she worked her magic, which turns out to have consisted of pulling really hard.

Through all the time (so far) that I had been poked, prodded, made to lie for hours in uncomfortable positions, and generally abused, I had uttered not a squawk, till then. The ring came off, and all the other unfortunate patients waiting for anesthesia were treated to some seriously blood-curdling vocalizations, which undoubtedly helped them ease into their oblivia.

One of these is not like the others.

Line In

The "central line" is a catheter that is inserted into a vein in the chest. For everything that happens from now on, anything that goes into or out of a vein will go through the central line, kind of like a USB port. My veins will finally get a little rest.

Inserting the line is a lightweight surgical procedure, done with sedation and local anesthesia, but a surgery nonetheless. So we have to compete for time in the OR with people who need immediate attention, and everything is scheduled at the last possible moment. In our case, that's after 8:00 PM the night before surgery. I figured I was low priority, and maybe the procedure would happen late morning/early afternoon.

So yesterday was our day off, and we visited Liz's brother Bill and family in Minneapolis. After dinner, we checked the automated telephone service to find that my scheduled report time was 5:45. AM. So we hustled back to Rochester (it's a little over an hour), leapt into bed, and roused ourselves shortly thereafter (no coffee for me!). After which we waited for anesthesiology to process me and everyone else. Prep for me began with a chest shaving and a nice beard trim (no extra charge), and I don't remember the rest, but now I am the proud owner of a double-lumen Hickman catheter (no idea how that differs from any other kind of catheter). It was all over by 9:00 AM.

My neck is a little stiff, and I have to figure out how to live with these tubes hanging on my chest, but generally I am still feeling fine. Tomorrow is "consolidation" -- a big dose of melphalan to shut down the remaining stem cells.

Collected

After two 5-hour sessions hooked up to an apheresis machine, I have managed to get enough stem cells collected for three transplants. The goal was 9 million, and I managed 8.89M yesterday (we requested, but were not granted, a recount), and a paltry 2.4M today, but that was enough to creep over the finish line. Which was good, because the long steel needle that goes in one arm (that can't be moved for 5 hours) had visited both arms, and I didn't have any interest in seeing it anywhere near me for a third day.

We had to skip the nutrition class in order to eat lunch (priorities!) and then hustle Rosie to the airport, where it turned out Delta could not produce a plane to make her connection in Minneapolis, but was able to produce a bus that took no longer to cover the distance. Then back to Mayo to find that the hastily-prepared afternoon schedule had come slightly unraveled: reporting for blood work to check liver enzymes, we found that the lab had no active orders, which seemed to be the first example of internal miscommunication we encountered. Upon reporting upstairs for our meetings with transplant docs and nurses, though, it turned out that the blood had been collected this morning ahead of the stem cells and the lab results were already in, sparing me at least one blood draw.

So now we have a day off tomorrow, the central line will be installed Friday, big chemo on Saturday, rest on Sunday, and transplant (day 0) is Monday, July 11. The best is yet to come.

Pre-transplant

I am in Rochester, Minnesota, at the Mayo Clinic, beginning the stem cell transplant process. The name "stem cell transplant" is maybe a little misleading, since it doesn't involve a donor (rather, I am the donor and the recipient). Sometimes it's called "high dose chemotherapy with stem cell rescue," which is more accurate but cumbersome.

The basic process is: 1) stimulate growth and "mobilization" of my bone marrow stem cells with injections of a drug called neupogen (filgrastim); 2) harvest mobilized stem cells from my blood (much less painful than getting them out of the marrow); 3) use a massive dose of a chemotherapy agent (melphalan) to kill off all the stem cells remaining in my marrow; 4) return the stem cells collected in step 2 to my blood, and encourage them to colonize the marrow and start reproducing, with the help of more neupogen; 5) ride out a few weeks of recovery time until the newly reconstituted marrow is functional enough that I can return to a more or less normal life.

I am on my third day in step 1, which is scheduled to last until July 5th (coincidentally the 30th anniversary of my marriage to my true soul mate and idol, Liz). Step 1 is pretty easy unless there are side effects of the neupogen injections (so far, just a headache). From all accounts, the steps get increasingly obnoxious as we go along, up until the last part of step 5, where things should start getting much better.

Rosie has been with us so far, and she brought a cold with her, residue of having moved herself from Durham to Boston. So when we go to Mayo complex and hang out in the waiting areas, Rosie dons a face mask to protect all the clinic patients (who are truly sick) from her cough. It seems strange that the youngest and healthiest among us is the one wearing protective gear.

Soon enough, I'll be the one with the mask. Should be interesting.

The Story So Far

I'm an epidemiologist who has mostly worked on studies of cancer and longevity.

Last year I discovered -- quite out of the blue -- that I had multiple myeloma. MM is a blood cancer that is almost certainly fatal, but there is a wide range of survival times, from a few months to 10 or more years. A few people seem to have been "cured," but for the most part they have unusual circumstances (like an identical twin to serve as a stem cell donor).

So much for the longevity research. There's a lot of really interesting work being done there, but I suspect I will miss the key advances in the field. Good luck to y'all.

So my plan here is to describe the experience of a scientist who knows a lot about how cancer works and a fair amount about how the biomedical research infrastructure works, but has no credentials (or expertise!) in any kind of clinical setting, when my focus has suddenly changed from finding patterns in the experience of hundreds or thousands of other people to one of me.

About the title of this blog . . . for about 12 years I worked as an epidemiologist in a research setting dominated by bench scientists who struggled to envision how "the Kerber lab" functioned without a visible laboratory space. Over the years I portrayed the "lab" as a computer, an MRI scan of my brain, or just a list of people we collaborated with. It was an inside joke, and not very funny.

Now I see myself as the only lab that matters to me. If I don't respond (or respond badly) to a drug, we swap that for something else. The past, or the projected future, is the control for the present. The control is not perfect, because we can't prevent any number of other things from changing over time, especially when I am an aging man with a deadly chronic disease, but there is a lot of information in the series of events and all the tests that go along with it.

Soon I will undergo a stem cell transplant. I hope to report on the stages, the experience, and the outcome, and a number of other things along the way. At the least, I hope it will reduce the quantity and bulk of emails to friends and family.