By Carol M. Ostrom, The Seattle Times –
SEATTLE — The most common method of extracting cells from unrelated donors for patients needing bone-marrow transplants should change in light of new research revealing higher complication rates than an older approach, said the head of clinical research for the Fred Hutchinson Cancer Research Center in Seattle.
Significant new research published Thursday in the New England Journal of Medicine — the first large, randomized study comparing the two sources of bone-marrow stem cells — showed patients who received transplants from unrelated donors’ blood were significantly more likely to get a complication known as chronic graft-versus-host-disease than those who received cells from donors’ pelvic bones.
In an editorial accompanying the study, Dr. Fred Appelbaum, director of clinical research at Hutchinson, said the blood-extraction method supplanted the traditional pelvic-bone extraction method about a decade ago. It is now used in more than three-quarters of the unrelated-donor transplants for patients with such blood malignancies as leukemia or lymphoma.
The complication, shorthanded as GVHD, means the transplant recognizes the patient’s tissues as foreign objects and attacks them. The condition can be relatively mild, or severe and debilitating.
“While this study should change practice, it will be interesting to see if it really does,” Appelbaum wrote in his editorial. “The benefits of peripheral blood are seen early, under the watchful eyes of the transplant physician, while the deleterious effects occur late, often after the patient has left the transplant center.”
About 5,500 unrelated donor transplants were done in the U.S. last year, and about 20 million potential unrelated donors are typed and listed in the registries worldwide.
The study, led by a former Hutchinson transplant physician, Dr. Claudio Anasetti, now at the H. Lee Moffitt Cancer Center in Tampa, Fla., looked at short- and long-term survival, transplant success and complications, both acute and chronic.
Patients survived equally well on both types of transplants, and the peripheral blood-derived grafts began doing their job faster and engrafted more reliably.
But GVHD can cause skin rashes, diarrhea and liver problems, sometimes up to three years after the transplant.
In an interview, Appelbaum said for the majority of patients undergoing unrelated-donor transplants, hip-bone derived marrow cells should now be the norm, although there still will be some patients for whom a blood-derived transplant is the best choice for medical reasons. For donors, the blood-draw procedure is less invasive than the hip-bone harvest procedure, which is done under anesthesia. But Appelbaum said the other type of donation isn’t without discomfort.
Those donating cells through blood must take a drug for several days to “mobilize” the marrow stem cells into the blood. The drug causes considerable bone pain, he said, and about two-thirds of donors take some sort of pain medication while they are getting the drug. In both cases, donors recover in about a week, he said.
“I don’t think this is going to make a big difference in willingness of individuals to donate — I certainly hope it won’t,” Appelbaum said. “Donors are wonderful people, highly motivated. These people are giving stem cells to save a life.”
Blood-derived stem cells slipped into standard transplant practice after researchers found that they did an excellent job when donor and patient were well-matched siblings.
After they found the grafts began working faster and there was less recurrence of leukemia, the practice became widespread in unrelated patient-donor pairs “without the benefit of large randomized studies,” Appelbaum said. “This is the first time we’ve had the chance to go back and do a randomized study.”
The study enrolled 551 patients at 48 centers around the U.S., including at Hutchinson, randomly assigning them to get either blood or hip-bone-derived cells, and followed them for about three years. Donors, who had signed up at 54 National Marrow Donor Program affiliated centers in the U.S., Canada and Germany, also were randomized. About 30 percent refused to be randomized, preferring one type of donation or the other.
At Hutchinson, which does about 550 bone-marrow transplants a year, about a third of those are from unrelated donors, a third are from matched siblings, and the rest from the patient’s own bone marrow, Appelbaum said.