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.

City Reformed Presbyterian Church

I just received a copy of the City Reformed Membership Letter for this month, and I saw that my family and this blog are mentioned, concerning my wife’s illness. So I thought I’d take a few minutes to give a brief overview of my wife’s condition and the needs that Pastor Matt was speaking about.

In June of this year, my wife Bethany was admitted to the hospital with an extremely low hemoglobin level – it was 5.7, when a normal level is about 12-15 g/dL. She underwent extensive testing and a bone marrow biopsy – there are many things that cause this type of severe anemia, but the biopsy came back positive. It took a while to come up with a definitive diagnosis, but what came back was “chronic myelomonocytic leukemia” (CMML), a very rare form of the disease that shares both “myelodysplastic” and “myeloproliferative” (MDS/MPD) characteristics.

A larger version of that process may be found here.

CMML, as a disease, is primarily something that older people get (median age is something like 74), usually as a result of a treatment from a prior cancer. Probably as a function of that, the prognosis is not for a long life (12-24 months).There is more information about CMML here for anyone who is interested.

Beth has so far received four “cycles” of a drug called Vidaza, which is part chemotherapy, and part therapeutic. It has the ability to “interfere with the leukemia process” and actually enable her body to return to somewhat normal blood levels. This hasn’t happened in Beth’s case, and she’s had to have numerous blood transfusions to bring her hemoglobin level back to tolerable levels. I have tagged entries about this under the tag Vampire Bride.

According to the medical information that’s available, “Bone marrow or stem cell transplantation appears to be the only current treatment that alters the natural history of CMML.” Interestingly, the brother of Dave Faith, an elder at City Reformed, went through this procedure several years ago and is doing fine.

Currently, my understanding is that the process of finding a donor is fairly far along, and there are four potential donors who are undergoing a final type of screening. (For anyone interested in this process, please visit http://www.marrow.org for more information). Once a donor is selected, we should begin the transplant process within the next six weeks or so.

I mentioned above that this is something that older people get. Beth was diagnosed at age 50 – she served in the Iraq War and was “in country” from April through September of 2003. A number of Iraq War veterans have come down with leukemia, and we believe that she was exposed to benzene, a known carcinogen, or other cancer-causing agents during her service at that time. Beth was recently featured in an article about this in the Pittsburgh Tribune-Review.

* * *

The City Reformed membership letter mentioned several of our needs. Our financial needs are summarized under the “Donate” button in the right hand column. As well, once Beth begins the transplant process, she will be a full-time inpatient at West Penn hospital for a week or two, and for the first 30 days after that, we will need to make daily trips to West Penn’s “Short Stay” (daily outpatient) unit.

Given the commute schedule (I’m going to try to get to work as often as is possible during this time, with an eye on our finances). During that time, we may need some help with the daily commutes, one way or another. But at this point, I don’t have any idea what that will involve.

We’ve also been approached about having meals prepared for us, and I believe that will be very helpful to us once we enter into the transplant schedule.

I want to say that we all are tremendously grateful to be a part of the City Reformed congregation. The response from Matt and the deacons, as well as other folks we know, has been overwhelming. We are most grateful for your prayers and concern and help during this very difficult time.

Sincerely,
John and Bethany Bugay

Please note: the “Chicken” entry nearby was a spoof of an academic research paper and presentation, and is in no wise representative of the other materials at this blog. 🙂

Account of a successful Bone Marrow Transplant

I may have posted some of this before, but there’s new information at the end, and it’s worth the telling.

At one point this past summer I logged into the discussion board at the Leukemia and Lymphoma Society. There are a lot of different types of leukemias, and CMML is one of the more rare ones. I came upon a thread entitled Looking for others with CMML.

(One writer writes, “There are so few people in the world with this disease, it is very scary”. Which is true.)

Most of the way down the second page of the discussion was a writer named “g-papaul”, who identified himself this way, with a post dated June 19, 2011:

I’m a 60 year old sales professional male getting annual physicals with blood tests. I was Diagnosed with CMML in Feb. 2011. My GP knew it required an oncologist and got the ball rolling. I’m from the Harrisburg, PA area and went to the best local oncologist I could find. The oncologist is affiliated with Johns-Hopkins, Baltimore, MD. My initial consultation with a transplant team at J-H was the end of March. March-April May were transfusions of blood and platelets as needed determined by my weekly blood draws at the oncologist. I also received 2 courses of Vidaza in preparation for the transplant. I was admitted to Johns-Hopkins on 6/13. On 6/15 started a 5 day run of Busulfan. Today 6/19 starts a 2 day run of Cytoxin. On 6/21 is the Bone Marrow Transplant from my donor brother. Then, 2 more days of Cytoxin. I start down the road to recovery and hopefully cured.

So he’s already into the “conditioning” phase – “intensive” chemotherapy, with the purpose of destroying the existing bone marrow, and two days away from a bone marrow transplant. Beth is due to follow a path like this one. He made several more postings. On July 8 we saw this:

I’m currently on DAY 17 after BMT. The BMT was uneventful and sort of just like getting another few units of blood. I rested for 2 days and then received 2 more days of Cytoxin. During the last day of Cytoxin you start to walk through the fires of hell. They start initiating bags of antibiotics, anti fungal anti microbials. I keep getting low grade fevers. They tell me it’s normal. Not all experience the same side effects. These drugs hit everyone differently. … I constantly feel like I have the flu. Just have to deal with it until around July 12. That’s the day projected to be the day my own marrow will be producing healthy cells.!

Later, he said:

The chemo side effects are all they say they are. … You feel like you got run over by a bus! Have to stay positive since they only last about 2 weeks. Then the miracle begins…Day 18 after transplant. Blood counts start appearing 50 here, 110 there and keep growing. Not by leaps & bounds but by 20-30 points. Several transfusions of red cells and platelets. A little rash here & there (a little GVHD is a good thing)…

I may have posted this much of his story already. Since that last posting, there was not another comment from him until yesterday. And here’s the key … here’s the thing we’re looking forward to:

I felt it was time to offer a follow up to my BMT to cure my CMML. I was released from Johns-Hopkins on August 19th to go home. Home…a wonderful place to recuperate. No more IV drugs that tear you up. Only a few in pill form to prevent various infections. We had a whole house HEPA filter system and a reverse osmosis water system on our well water installed. I DO NOT leave the house or go in the basement without an N95 mask. If I’m going to the store or doctor I wear disposable gloves too. Wash hands frequently. I finally started eating the last week of August after 6 weeks of eating nothing. I lost 80 LB and feel great…. The diet has been expanding but not my waist line. I’ve learned to eat all over again. I will not return to 290 LB!!! There are positives out of this ordeal. My Osteo arthritis is gone. (They said it could be temporary or long term). I don’t need Blood Pressure or Cholesterol meds anymore. I don’t need to sleep with a C-PAP machine. All of the anti bacterials & fungals fed me IV cured my athlete’s foot and one nail infected with a fungal infection…they rebuilt me! I currently visit my local Oncologist every 2 weeks for chec ups. He says the recovery is text book.

There’s not a lot of good medical news about CMML. But here’s anecdotal evidence that the process works, and works well. There are a couple of differences with our situation. Most notably, this individual has a related donor. But it’s a very hopeful story.

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.

Three reasons why I’m writing this journal

1. We want to persuade the press, the VA, the military, the federal government, that there are consequences to the military’s policies. Even the little ones.

  • In March 2003 Bethany completed the Army’s “Field Sanitation Course” (see image below).
  • In May 2003, especially, when Beth was part of an advance group, she was heavily involved with “burning trash and human waste”, shown in the photos below.
  • She wrote about it in a letter dated March 14, the scan of the hand-written page.
  • This activity, “burning diesel fuel” is known to produce the chemical Benzene.
  • Benzene is a known human carcinogen. And, being directly involved with this activity, Bethany was heavily exposed to the benzene that was produced.
  • Thus, we hope to persuade that, because of the U.S. Army’s official policies, Bethany was exposed to Benzene in large enough quantities that it is clearly identifiable that these incidents are the cause of her current cancer (leukemia), as well as similar ailments in other soldiers who have served in Iraq and Afghanistan.

2. Beyond persuading the official parties listed above of the sequence of events listed above, we hope to reach a wide and sympathetic audience, and persuade them that we continue to need financial help as we work through this time in preparation of a bone marrow transplant.

3. We want to tell a compelling story of a family’s struggles through this past decade when it was said that “9/11 changed everything.”

Beth was trained for "burn pit" activity
Burning trash and human waste
Describing the activity in a letter, dated May 14, 2003

More photos are here:
http://www.facebook.com/BethanyBugay

Please share this information. Hover over the “share” button just below this paragraph. You’ll see the various ways in which you can share this message with others. If anyone knows of other soldiers who have come down with leukemia because of burn pit activities, we’d love to know that story. We’d love the opportunity to put our voices together and tell a larger story. We’d love to make certain that this story gets the kind of publicity that it deserves.

It’s going to be a busy week

It’s going to be a busy week for us. Beth has a doctor’s appointment today and our big “intake meeting” with the transplant folks tomorrow. I expect that we’ll learn what treatment is going to be like for the coming months, the status or our donor search, maybe get some clarifications on the diagnosis and prognosis, and a lot more. Meanwhile, Beth begins Vidaza, Cycle 3 this week as well.

Beth had a pretty good weekend; we visited my cousin Walt, who is also a veteran; he recently had heart bypass surgery, and he gave us a pretty good report about how to navigate the VA system. There’s one difference: he’s a Vietnam veteran, and much of what the VA will cover from that conflict is settled; we are still waiting on a study by the VA on the topic of the “Long-term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan”. Stay tuned.

The car situation is going to be much complicated from here out, as the older guys start school today; two of them will begin the CCAC Nursing School program, and a third is starting general studies there as well. There are five of us going different places, and three cars. The younger kids start school next week. Fortunately, recent changes in the school bus schedules don’t seem to have affected us.