“Technically, the first day of engraftment”

The doctor was in, and even though Beth has been feeling pretty bad, he said, “the worst is over”.

The doctor just told us that technically, today is Beth’s first day of engraftment. Her white cell count was 2.0, so she’s no longer neutropenic — can eat anything she wants, there is no need for us to maintain a sterile environment at home, etc. She can fight the fevers on her own.

She’s feeling quite a bit of bone pain, still some minor fevers and headaches, but as the doctor said, “the worst is over”. The nurse here, too, said that one thing they don’t say enough about is that this second week past the transplant is the worst. But she has no signs of GVH at the moment — liver, GI tract, and skin are at an acute risk at the moment, but no signs of it. I guess there are still opportunities for complications, but the worst is past.

The most annoying thing is the mucositis — the mouth ulcers. They’re affecting her ability to eat, giving her pretty decent heartburn. She’s definitely been through the wringer.

Engraftment is taking place

I just got back to the hospital. Beth had only one mild fever this afternoon. Her white blood cell count was .10 yesterday and .29 today (for normal folks it’s over 5.5). But the increase in white cells is the first sign that engraftment is taking place. And it means she has her own ability to fight off infections. So much so that they discontinued one antibiotic, the vancomycin.

The transplant and initial complications are past; now we need to watch and pray

I’ve been putting up a lot of short posts (I’ve primarily been using my old iPhone), and now I’ll just summarize the events of the past couple of days. There are photos throughout the posts that appear down below.

Beth received her transplant, from 9:45-10:30 on Wednesday evening, December 14th. She received a very high number of stem cells (the range is 4 million to 8 million cells per Kg of body weight) — she had a young, strong donor, and she got the 8 million.

After the infusion of the new stem cells, she had a somewhat violent reaction, which lasted most of the night and the next day. Her fever went up to 103. Everyone’s initial response (all the medical folks) was that she was having an infection, and that is an appropriate place to look. Beth’s response was not common, but it happens. She seems to have settled down from that. They are continuing to give her two different antibiotics, Vancomycin, for staph infections, and Cefepime, which is good for pneumonia.

The next challenge will be that the effects of the chemotherapy (and I’m guessing they mean the Busulfan) really kick in on days 7-10. So we should be entering that phase now.

The purpose of the chemo was to destroy Beth’s existing bone marrow. This doesn’t happen all at once, but it happens over these 7-10 days. One of the doctors said that the existing marrow, while not yet “destroyed”, has been affected by the chemo and is not able to reproduce itself. And that’s where the new cells came in.

The new cells will begin to grow into new bone marrow. In the next couple of weeks, doctors will be looking for signs of engraftment, which occur probably during days 7-10 after the transplant. (These 7-10 days are different from the days 7-10 of chemo.)

30 days down the road, they will do another bone marrow biopsy and Chimerism testing to make certain that existing bone marrow is 100% donor and 0% Beth. If it’s something other than that, it would be a bad sign.

So we are not yet out of the woods. There is a 35% chance of relapse. But we know, too, that during the conditioning phase and afterward (by tweaking the response to the graft-vs-host effect – the effect by which the new tissues perceive Beth’s old marrow as enemy and continue to destroy it), the hope is that we achieve that 100% cure. But it’ll be a year or two before we know that.

The end is near

It’s about 6:00 now; I’m going to head back to the hospital to spend the night with Beth (I went in to work four hours today, and got a few things done).

Beth is going to get her first dose (of three) of Thymoglobulin, which, I understand, suppresses the immune system. She’ll also get the last doses of Fludabarbine and Busulfan. They’ve given her some “pre-medications”, which had her sleeping all day. We’ll see how she handles all this tonight.

For the next two days, then (the 13th and 14th), she’ll get the Thymoglobulin and the total body radiation, and the donor’s stem cells should arrive here the evening of the 14th. By that time, our hope and expectation is that the leukemia-producing bone marrow will be completely destroyed.

Of course, then we have about a year dealing with issues such as engraftment, infections, and graft-vs-host symptoms, but the end of the leukemia is near.

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.

Bone Marrow Transplant

According to our doctor: “this is the only curative option”
In spite of all that has happened, we are still at the beginning of this process. What has happened up to this point is merely preparative. With this disease, all roads lead to the bone marrow transplant.

Standard chemotherapy won’t help her. Bethany’s bone marrow is damaged, so even if chemotherapies could be given that would put her into “complete remission,” that is, to eliminate all the cancerous effects from her blood, it wouldn’t last, because her bone marrow is damaged, and her damaged bone marrow would continue to replicate the leukemia process. My understanding is that these treatments work for a while, but they will eventually fail.

So, as Dr. Rossetti reminds us, “The only curative option remains allogeneic (non-related donor) transplantation.” And as a part of this process, there are still several milestones that we need to look forward to.

Finding a donor
Even though we have a number of potential donor matches, we still haven’t found that ideal person. They are looking for someone who can match on 10/10 DNA markers. So far, there are six potential “10/10” matches, but none of these is ideal. Most, for example, are older females, who have had children; antigens developed during pregnancies that can contribute to complications during the process that follows.

The dangers, as I understand it, are not that the cancer is less cured. The danger is that the graft vs. host complications will be more severe. So the donor search process is an attempt to minimize that part of it.

The “Bone Marrow Transplant” (BMT)
This is the biggie. The bone marrow transplant is a “transplant” in the same sense of a kidney or heart transplant. Something old is removed, and something totally new is put in. However, unlike a traditional transplant, which is usually a one-time surgical procedure, this one is a longer term process. Much longer.

To get out the old, they can’t just open her up and take out the bone marrow. They have to kill it, and they’ll do it with “intensive chemotherapy” and full body radiation. This process will last a little over a week, and if it sounds harsh, it is.

Simultaneously, the selected donor will be given Neupogen injections for 5-6 days, to prompt his or her stem cells to move from the bone marrow to the blood; on day five of the Neupogen injections, they’ll be hooked up to a dialysis-type of unit; blood will flow out one arm, the stem cells will be harvested by a machine, and then the blood will flow back into the other arm.

When enough stem cells are collected, the bag of stem cells will be flown into Pittsburgh, where Bethany will have already been prepared by the process described above. The implantation of the cells process itself is simple. Some of the blogs I’ve read have even described it as a bit of a let-down, just something like another blood transfusion. But the results are spectacularly different.

“Engraftment”: First 30 Days
Many things can go wrong during this first phase. If we were to go to UPMC, this would be an inpatient process, lasting four to six weeks. At West Penn, they say that patients respond better by being home. (Dani wouldn’t be permitted into the hospital; they’re pretty firm about that.) So Beth will be permitted to go home every evening, and then will need to return to the medical short stay unit, every day for 30 days.

(Note to Highmark: Our understanding is that we will be required to pay the $30.00 co-pay each and every day we show up there. Is there some way that you can streamline this clunky procedure? West Penn is already saving you oodles of cash by making this an outpatient procedure; the least you can do is streamline your paperwork to make it easier for a patient who’s near death.)

During this time, the chemo is still raging; Beth’s hair will fall out, she’ll experience nausea, vomiting and diarrhea, won’t be able to eat. Her immune system will have been wiped out. She’ll be ultra-sensitive to infections, and it’s very likely she’ll need to be admitted to treat infections anyway.

The expectation is that the new stem cells will go to where they’re needed most, that is, into the now-dead bone marrow, and set up shop. This is called engraftment. As part of the daily checking, is checking for signs that this is happening. There is about a 5% chance that engraftment will fail.

Acute “Graft vs. Host Disease” (GVHD): 30 days-100 Days
During this time, Beth’s immune system will be severely depleted, but the expectation is that the new stem cells will have their own immunity. To some degree, this is very desirable, because the new immune system can kill off any remaining cancer in the bone marrow.

But on the other hand, the new stem cells can, to one degree or another, begin to reject Beth’s own tissue. This is called Graft vs. Host Disease. Symptoms can range from simple skin rashes and mouth sores, to more complicated issues dealing with organs such as kidneys, liver, and lungs. Often, I am told, the symptoms from the anti-rejection drugs can be worse than the GvH symptoms themselves.

She will also be susceptible to infections during this time period, including pneumonia, which can be life-threatening.

Chronic GVHD: +100 days to One Year
After 100 days, the new stem cell engraftment will have begun producing its own new stem cells, and for some reason, a whole new round of “rejection” can occur. Too, some of them can be fatal. Marrow.org has prepared a brief presentation that walks through this phase of the process.

The ideal outcome
The ideal outcome, then is simply to get all through all of this. Most of the GvH symptoms will diminish over time. There is still some danger of relapse at this point. But from what Dr. Rossetti tells us, if you can get past the two-year mark, the chances of living out a normal life-span are excellent.

One survivor who I’ve been in contact with has told me about the “survivor dinners,” where “There are a lot of people who are many years past transplant and look great and do not have any ongoing issues”. That’s something we can look forward to.

Here, again, is the prognosis:

  • 30% cure;
  • 20% immediate complications;
  • 15% major longer-term complications;
  • 35% chance of relapse.

Please keep us in your prayers, and please, also, consider helping us out financially.

This gets bigger the further we get into it

At first it was a struggle just to learn what was wrong. Last Monday, after about three weeks and two hospital stays, we finally learned what the diagnosis was going to be. (And two separate biopsies have confirmed this).

The other night, Beth got a call from someone in a support group sponsored by the Leukemia society, from a woman who had undergone this procedure probably about eight years ago. She is experiencing some ongoing “graft-vs-host” symptoms, and so Beth asked me to look them up.

In my Googling, the site marrow.org kept coming up: with an excellent overview of the procedure; with an excellent overview of the follow-up treatment; and, in a dimension that I’d thought about but which really only hit me now for the first time: the financial aspects of it.

As it turns out, this Vidaza treatment and even the period of intense chemo and radiation known as “conditioning” are only the tip of the iceberg with respect to this entire process. The real “marrow” of the thing, so to speak, occurs post-transplant.

Up to a point, you don’t even know the right questions to ask. You’re just trying to find out, “what’s the next thing we have to do, we want to get it right.” Yesterday I had my first glimpse of what might be termed “the long view,” and I can see now that it’s just going to take a while to get my head around the process.

Here are just some of the steps:

Some time during days 30-100, you “will probably” get to go home from the hospital, but still there, will likely be almost daily outpatient follow-up. In the “long term survivorship” document, it is said, “by one year after transplant, many transplant survivors are able to take part in their usual activities, such as work or school.”

And none of this is to talk about the financial considerations that go along with this whole process.