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.