Overnight and the near future

I spent the night at home last night for the first time in nearly two weeks. Beth seems to have stabilized. I’m going to give her a call later this morning. The plan is that they will remove her “triple lumen catheter” today – the doctors sort of having isolated this as the source of her recent infection – and they’re going to put another one in. It should be possible for her to come home after that. The kids have all been wonderful. Everyone’s been pitching in – giving rides when needed, cooking meals, cleaning the house (a bit), washing dishes, getting the garbage out.

Beth is not out of the woods yet, medically, although there is great hope. Still, GVH can cause pneumonia and organ failure leading to death, and even prior to that, she’s still going to be neutropenic for the next week or two. And we still have the daily trips to the short-stay unit for about three more weeks. So I’m headed for work this morning, and I’m going to try to work at least half-time for the next couple of weeks. My two older boys have cars (for which I still pay the car insurance); they have both volunteered to share the rides to and from the hospital.

A few more things we learned yesterday

Now that a donor has been recruited, Dr. Rossetti thinks that we will be able to “have stem cells by mid December”. No dates are firm yet, but we should be able to have a firm schedule in place by the end of next week.

Beth’s blood counts continue to be critically low – her white blood cells yesterday fell below 1.0 (“.94”) for the first time since I’ve been watching the numbers. And as I noted, her hemoglobin was 7.2, and her platelets were only 18 (again, lowest I’ve seen them). So today, Tuesday, she’ll go to Jefferson Hospital for her (7th of 7) injections of Vidaza, for two or more units of blood, and also, for platelets.

Beth’s bone marrow is defective, and every stem cell she produces is defective, and so the goal over the next few weeks (including the “intensive chemotherapy” and radiation) will be to bring her “as close to zero bone marrow” as she can get. The Vidaza, while not enabling her to produce good blood cells as promised, has at least gotten her most of the way there already. And that’s a good thing. [Also a “God” thing, as I had written at first.] The reason you want all of it gone is to reduce the chances of relapse down the road. And in addition to the “intensive chemotherapy”, the full body irradiation “cuts relapse rates 20%”, according to Dr. Rossetti. Every little bit helps.

Once the new stem cells are transplanted, then Beth’s numbers should begin to go in the right direction. Her white cells should begin to recover within 2-3 weeks. Engraftment should occur on or before day 30. Hemoglobin production should start in about three months. Anti-rejection drugs will be administered between days 35 and 90 – more or less to either to control or enable some “graft-vs-host” (GVH) effect. To some degree, the GVH has a “mopping up” effect – the immunity of the new stem cells will target and destroy any remaining defective bone marrow, or any remaining defective stem cells.

Too much, to be sure, can cause problems. But this is what the donor search has been all about: matching on precisely the right DNA characteristics, to give just enough, but not too much, GVH.

How the donor DNA match works

HLA Markers
When we talk about finding a “donor match” for Bethany, I’ve been using the term “DNA markers”, which is not technically inaccurate, but it is probably less specific than it could be.

What they’re really looking for are “HLA markers” or “human leukocyte antigen” markers that match. These markers “contain a large number of genes related to immune system function in humans.” And “the immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person’s HLA type belongs to that person and therefore is not an invader.”

These are the little guys who can both kill off any remaining cancer cells, and cause the maddening array of graft vs host (GVH) difficulties that bone marrow transplant (BMT) patients must deal with.

The diagram here shows you probably as much as I could ever hope to tell you about them. I wish I’d had this diagram when talking with Renee at our first intake meeting. These markers are key among the ones that need to match in order to find a suitable donor.

As I’ve noted, Bethany has a rare “C” marker. I could not honestly tell you what that means, other than that it is a very important one. I am happy, at this point, to know as much as I do about it.

The last time I talked with Renee (on Monday), there was one person (among the four remaining candidates who matched 10/10 of these HLA markers) who had already submitted to the further blood testing that was needed, and a second one was scheduled for this testing.

Again, my understanding is that all of these four individuals had characteristics (older, females with multiple antigen-causing pregnancies, etc.) that made them less than ideal candidates. Though, as 10/10 matches, they are suitable.

There is a second group of four individuals, who match on the critical “C” marker, but may be mismatched in some other way. (These individuals might potentially become 8/10, 9/10, or 10/10 matches, but at least they will match the critical “C” marker). These folks are also being asked to undergo some further testing.

It’s a big process, and honestly, I wish things were a bit further along than they were. But 10 years ago, I don’t believe Bethany would have had the option of a transplant. She would simply have been forced to live out a short remaining life span, full of blood transfusions and a chemotherapy regimen that would eventually fail.

What’s the greatest danger? (Part 2)

“Transplant is the only cure”
Once the decision has been made to go with the bone marrow transplant or stem cell transplant, an entirely different set of dangers arises from those faced because of the leukemia. In principle, the existing bone marrow is destroyed, and so the leukemia is destroyed. There is a significant possibility that it will return, but that danger is down the road.

The goal of this transplant is to completely eradicate her old, damaged bone marrow, and to replace it with new healthy and growing marrow that is capable of producing untainted blood cells. There is a great deal of danger in this process. Sometimes it seems to me that this is a case of “the cure is worse than the disease,” except the disease, CMML leukemia, is very bad indeed.

To eliminate the old bone marrow, Mom is going to be put through a regimen of “intense chemotherapy” (and note that the regular old kind of chemotherapy is bad enough for most people), with chemotherapy drugs with names like Fludarabine, Busulfan, and Thymoglobulin. These are still so far down the road that I haven’t yet looked them up. Then there are two day’s exposure to “total body irradiation”.

All of this will occur over a period of 6-8 days prior to the actual “transplant” (which in Mom’s case is then an infusion or a “graft” of stem cells from a non-related donor). In this process, not only is her bone marrow destroyed, but her immune system is destroyed.

For the first 30 days or so after the transplant, there is a danger that the graft will not “engraft”, that is, it will completely reject her system, but that risk is controlled with drugs, and it’s minimal. The larger possibility is that, with her depleted immune system, she will suffer from an infection. It can be bacterial, or viral, or fungal; she will likely develop “mouth sores”, she won’t be able to eat, and she’ll experience nausea, vomiting, and diarrhea. There are dangers of liver and kidney damage, and also pneumonia, which can be a killer.

There are drugs and antibiotics to deal with these. But still, the first 30 days is only the beginning.

When the “graft” becomes “engrafted,” there is a whole new set of dangers. Mom will have no immune system, and in essence, the “graft” will be in charge. The “graft” will have its own immunities, and they will have their way with her. There is a danger that they will reject her, in large and small ways. This is called graft vs host disease (GVH).

True, some of this GVH effect will do a clean-up job on any leftover bone marrow or leukemia from the old regime. In fact, “graft vs host” is what provides some of the magic of this transplant process. It’s often the final nail in the coffin of the leukemia.

Unfortunately, it’s also a killer in its own right. There are two phases: “acute”, while the actual “graft” is still moving around in there, and also “chronic”, beginning at approximately 100 days after the transplant, when the “son of graft” cells are taking over.

In all, the GVH period can last up to a full year or more. Symptoms may be as mild as a skin rash, but GVH can also affect major organs, and I have a friend whose wife died from GVH complications some two years down the road.

The good news is that, if Mom makes it down the road that far, there is an excellent, excellent chance that she will have beaten the leukemia and can look forward to a normal life span. There may be some lingering GVH symptoms – we’ve encountered a couple of people who can’t make tears.

But that’s a relatively minor thing to live with, compared to leukemia.

A tentative transplant schedule

Over the last couple of days, I’ve been going in to work from 5:00 am till 9:00 am, to get in four hours, before leaving to take Beth to her Vidaza treatments and doctor’s appointments. Wednesday and Thursday she will only have Vidaza treatments, so I’m going to continue go in and work very early in the morning, then leave to take her to her treatments, and then drop her off at home and go back to work for the afternoon, to get full days in. We’ve had to do it this way because all of the older guys started school this week, and I’m trying to take off as little time as possible.

One of my greatest fears is the prospect of taking unpaid time off of work, and thus not having an income during the critical time when Beth is most heavily involved in her transplant process. We learned quite a bit about the transplant procedure and schedule yesterday.

First, there are at least five potential donors who matched on 10 of 10 HLA (DNA) categories. Not all of these are ideal simply because of their age (in their 50’s), but they are continuing to search and there may be more of these folks, as well as some 9 of 10 matches that may be more well suited physically. And again, there needs to be some further testing for all of them. (Apparently in one of the more important categories, Beth has a somewhat rare combination of markers).

Beth’s oncologist, <a href=”http://www.wpaci.org/specialists/index.cfm?sh=s&d=348&p=1253″>Dr. James Rossetti</a>, told us that, because of Beth’s <a href=”https://johnbugay.wordpress.com/2011/08/24/an-important-update-to-the-blood-charts/”>recent progress</a>, we have every reason to expect that she can “move to transplant” as soon as we find a suitable donor.

Here’s the rough transplant schedule when that occurs:

  • Daily Outpatient treatment (3 days, -9 to -6, treatment with Kepivance)
  • Inpatient chemo and radiation, (6 days, -6 to -1, Fludarabine, Busulfan and Thymoglobulin, and two days of total body irradiation).
  • TRANSPLANT (Day zero)
  • Daily Outpatient – from approximately days +1 to +30. Daily monitoring (five- to 10-hour stays) at <a href=”http://www.wpaci.org/index.cfm”>West Penn Hospital’s</a>Medical Short Stay (MSS) unit. There is also a 75% chance of an infection that will require a readmission.
  • Days +31 to +100 – twice-weekly office monitoring.

If there is going to be a relapse, it will most likely occur during the first year after transplant. Two years out from the procedure, the chance of a relapse is minimal (just 1% To 2%). And five years out, that risk is almost nonexistent.

Beth has a roughly 15-20% chance of mortality during this process. In the <a href=”https://johnbugay.wordpress.com/2011/08/23/back-home-from-the-intake-meeting/”&gt; mortality chart provided below</a>, the “immediate complications” include all kinds of infections, as well as acute Graft vs Host (GvH) complications, some of which can be fatal. Some chronic GvH complications can also be fatal, but most are treatable with medications.

The ideal outcome will of course be that Beth can live out a long and healthy life span, with minimal requirements for medications to control GvH symptoms (which can also fade over time).

Early on I told Beth that this was not a disease that she’s temperamentally suited to have. She’s always been more of a person of action: “tell me what to do, and I’ll go and do it.” But there are many uncertainties with this process. Those uncertainties are hard to deal with, but the meetings we had yesterday helped to clear up many questions we’d been having.

Interestingly, Dr. Rossetti is a former Roman Catholic and a convert to Eastern Orthodoxy. We had a bit of a conversation yesterday about church fathers and ancient Rome and T.F. Torrance. Pretty cool.