Why are matched unrelated donations (MUDs) better than donations from siblings or children?
They’re not.
For blood disorders like leukemia, they’re the next-to-last or last resort if a patient must have a transplant. Matched unrelated donor transplants have a graft versus leukemia effect, but there is also a graft versus host effect. Outside of an identical twin (syngeneic) transplant or a reinfusion of one’s own cells (autologous transplant), the body’s defenses may be mobilized against a stem cell or marrow graft and so a MUD patient experiences graft versus host disease (GVHD) the majority of the time. Human leukocyte antigen (HLA) typing checks whether the proteins on the surface of the blood cells will be attacked. Sibling donors do not always have a perfect HLA match, but because a sibling has common genetic material from the parents, there is a decent probability of a good enough match. With a MUD donor, the chance of GVHD is more likely. Even with immunosuppressive drugs, GVHD can be fatal. Patients receiving MUD grafts have a higher rate of post-transplant complications and a higher short-term and treatment-related mortality than sibling grafts for identical diagnoses.
A child as a donor for a parent is usually no better than a MUD because the child has a mix between her mom’s and dad’s HLA typing.
That said, signing up to be a donor can definitely save someone’s life. Not everyone has a brother or sister with a good HLA match and so a MUD transplant is the only option for many patients.
May I ask where you got your information about MUD transplants being better than siblings? I work at a large transplant center (City of Hope) and that’s not our historical experience. If MUDs were better than siblings, then we’d do MUDs all the time.
Rather than starting a new thread I’ll just hitch a ride on this existing one to ask a question I’ve been pondering: namely, is it worth the effort for a soul as genetically diverse as myself – English, German, French, Polish, Portugese, Slovenian, Itallian (and the red beard suggests a little Norman invasion) – to get tested for marrow donation when it’s pretty unlikely that there’s as odd a mix as myself? I understand that the initial protein matching protocol is pretty good, but that it usually falls apart upon closer scrutiny even within narrow genetic communities.
I saw a memo of a conversation between my mothers doctors, one of whom seemed to feel that a MUD was a better option for transplant, despite the fact that she has been saving stem cells since the time she went into her first remission, about 3 1/2 years ago (he feels that there is a chance that they are polluted with leukemia cells, and that the chance is not worth taking at this point. He basically ruled out her stored cells as an option at this point in time.), and that my uncle (her brother) has offered to donate marrow if necessary (he made no mention of that option, though he is aware of my uncle’s willingness). In either event, a transplant is not in her immediate future. They do not think that they were able to erradicate all the leukimia with one round of chemo. They discharged her for the holidays to get her strength back for a second and possibly third round before they will decide on a transplant. Please do not infer that I think her doctor is incompetent; in fact, his reputation is stellar. I may have misread the memo or misunderstood it. It’s been a heady week.
Inky- you have a valid point. From the (USA) National Marrow Donor Program (NMDP) website, their annual report shows that the majority of marrow donors in their registry don’t end up going to a marrow harvest for a sick patient. I’m not sure if I’m reading their annual report statistics correctly, but it looks like only about 13% of the overall marrow donors are used for a search, and 0.2% - 0.3% get worked up for apheresis. They break down the donors by broad race/ethnicity groups. To me, this supports what you’ve conjectured. I hope that this doesn’t dissuade anyone from considering to be a potential donor. To a patient, your marrow could give them many more years of life, even though the odds may seem unlikely.
Casey1505, I’m so sorry about your mother. Her doctor is correct and I should have been more explicit. What I should have said is that if a patient has both a sibling donor with a good HLA match and a matched unrelated HLA match, genetically the sibling graft will have a better clinical outcome than the MUD graft. That is, my statement was based on having the choice between a sib donor and a MUD donor: the sib graft is preferable.
In your mom’s case, the doctor is right. For a leukemic patient, with say, AML, an autologous transplant (using the patients own cells for reinfusion) needs to be screened for blasts. If there are blasts present, then the chemo was in vain since you’d be putting diseased cells back which would probably grow more diseased cells. At our center, we have many AML patients who get autologous transplants but their stem cells are checked for blasts. Your statement is right in your mom’s case: between a choice of an autologous transplant containing blasts and a MUD transplant (with presumably no blasts), the MUD is a far better option. For our center’s ALL transplants, they are uniformly sibling or MUD donors.
I’m not sure why the physician would rule out your uncle as a donor out of hand, and maybe he wasn’t. He may have wanted to start the MUD search immediately because it takes a few months. Since your uncle is available for typing much sooner than a NMDP donor, he’ll eventually call in your uncle and get him typed if a transplant seems necessary. He can then compare all of the HLA results at once and then pick the best one. If your uncle is a match, I would guess that he would be the donor as opposed to a MUD donor since that would give your mom a better prognosis.
One other thing: if she’s not on a clinical trial, she may want to consider one if her hematologist thinks that it’s appropriate. If you check the NIH’s clinical trials site, you may find one for which she’d be eligible.
Very best wishes to your mother and your family.