The Risks Associated with BMT

"We can complain because rose bushes have thorns, or rejoice because thorn bushes have roses.” 

― Abraham Lincoln

Be forewarned: this is scary stuff, so don't read it if you really don't want to know. I prefer to know where the thorns are located.

A stem cell transplant is a risky procedure. There are different reasons people have stem cell transplants and so the treatment is tailored to their condition. For example someone with leukemia needs to have the disease largely eradicated as part of the process so that it doesn't come back. For immune system deficiencies it's a little different, all they want to do it get the new stem cells to engraft and start functioning; there is no underlying blood disease to treat.

In addition to the underlying reason driving the need for a transplant, there is also a difference based on who the donor is. If you are lucky enough to have a HLA-matched sibling as a donor it's know as an "allogenic" transplant. If the donor isn't a sibling, then it's called a "matched unrelated donor transplant" or MUD-BMT. At NIH, additional steps, namely total body irradiation, are taken to increase the odds of success for a MUD-BMT.

As a result the risks vary based on the details of the procedure.

Here are the risks as I know them presented in order of the procedure. I don't really know the relative risk levels.

Pre-conditioning:

There are a lot of test that happen in the week leading into the "conditioning regimen". There are minor risks associated with each of the tests. The most notable risk, and one that will go on until the end of the 4 months of treatment is the Hickman Intravenous Line. This is a long term catheter than provides access for drawing blood, injections, intravenous feeding (if necessary), etc.The placement of the catheter has risk of collapsing a lung, puncture or infection. Longer term, there is risk of infection at the site.

Conditioning:

The conditioning process is intended to knock down Elise's immune system so that the donor cells can engraft after they are transfused. The conditioning protocol consists of a series of two different chemotherapy drugs followed by total body irradiation and then a long-term immunosupressant.

The first chemotherapy drug they will use is alemtuzumab ("Campath-1H"). This drug is a powerful immunosuppressant. "The drug is typically well tolerated but can cause some side effects..." It has the typical potential minor side effects (diarrhea, headache, shortness of breath), but it also has some striking rare side effects ("fatal reactions") that they pre-medicate to prevent and then monitor closely during the infusion process. The biggest risk is the intended action of the drug: it knocks down the immune system and therefore you are open to infections for "a number of months after receiving". Another recently reported potential side effect is "abnormalities of heart function". Elise's heart function will be evaluated with an echocardiogram and 24-hour Holter monitor as part of the work-up and then closely monitored after treatment with similar diagnostics.

The second chemotherapy drug they will use is Busulfan. "At lower doses, it tends to kill mostly myeloid-type (germ fighting) cells of the immune system." It has a list of possible side effects that range from nausea and vomiting to infertility and cancer (!) It can also cause seizures, so as a precaution they'll also be using an anti-seizure medication called clonazepam. A rare side effect of busulfan  is scarring of the lung tissue that can develop as late as 4-10 years after receiving the drug. Elise's protocol will use lower doses of Busulfan than a patient with leukemia would receive, but I've read that the drug is hard to dose properly: high doses cause problems, and too low a dose can lead to graft failure.

The total body irradiation (TBI) is apparently much lower levels than a leukemia patient would receive, but much higher than anyone in the general public would get at any point in their lives. The risks are nausea, vomiting, mouth sores, a host of organ diseases, and sterility. They've said there is a good chance Elise won't be able to have kids. I've also read that TBI can affect cognitive ability at higher doses, but the NIH consent doesn't mention this.

One thing they have told us is that Elise will lose her hair temporarily as a result of the conditioning treatment. She's looking on the bright side of things though: she's happy that she won't need to shave her legs for a while.

The final drug they start just before transplant, Sirolimus, really isn't part of the conditioning regimen, it's used to help keep Elise's T-cells from fighting the donor's cell. Elise will take this drug for up to six months after the transplant. The direct side effects are "mild" and may include nausea, vomiting, joint pains, ... Because Sirolimus is an immunosupressant, the most likely risk associated with it is increased susceptibility to infections. Additionally, because it suppresses the immune system there is the rare chance of developing lymphoma or other cancer.

Post-transplant

Following transplant there are two main risks: infection and graft-vs-host-disease (GVHD). Infections result from the fact that the immune system has been seriously knocked down and then continues to be suppressed with medications so that the donors cells can engraft and become well established. The infections can come from just about anything, even things that normally wouldn't make anyone sick. During the first several weeks post transplant, Elise will be in isolation. After the donors cells start to engraft she will gradually be able to come out of isolation and eventually be discharged to live with us in an apartment in the local area. She'll still need to be extremely cautious (wear a mask, avoid public places, wash her hands continuously, etc). She'll also be taking antiviral and antifungal medications to help defend against those types of infections.

GVHD is when the body and the donors T-lymphocytes attack each other. It occurs in about 30% of transplant patients and can range from mild to severe, even fatal. It may be as mild as a skin rash that doesn't require treatment to liver and kidney damage, although the latter are more rare. Depending on the situation, they use a variety of medications to treat acute GVHD.

Another infection that may occur is cytomegalovirus (CMV). While there are innumerable potential infectious agents, this one deserves special mention because it was a serious problem in the earlier days of transplants. It can still be a problem, but they screen continuously for it post-transplant and are better prepared to treat it if it occurs. In fact it's so prevalent in humans that they actually screen for it before the transplant in both the donor and recipient and try to match donors to recipients with this as a factor when possible.

Long-term

GVHD is broken into "acute" and "chronic". The chronic GVHD can develop later and continue for long periods. The risk of chronic GVHD is on the order of 5-20%. There are treatments that are used, but these treatments aren't always successful.

Another long term risk is graft failure. Rarely this can happen quite some time after transplant. If this occurs, then Elise's own immune system should take over. But in that case she'll still have CGD and all the problems that we're trying to cure with the BMT.

Finally, the consent paper work says: "Because marrow transplant affects the entire body, a comprehensive list of all side effects that have ever been encountered after marrow transplant cannot be made...Conventional allogeneic transplantation carries about a 40% chance of death from complications of the transplant. Although we have good reason to believe that the nonmyeloablative transplants confer a much-reduced death rate, the procedure nonetheless carries some risk..."

After all the discussions and reading, as best I can tell, Elise has about a 85-95% chance of a positive outcome. I'm trying hard to focus on the probability of a beautiful bloom.