Mismatched Bone Marrow Transplants Effective in Acute Leukemia

For many leukemia sufferers, bone marrow transplantation is their only hope. Unfortunately, for about 40% of patients with terminal disease, a perfectly matched donor cannot be found

Now, scientists from the Weizmann Institute of Science in Israel and Perugia University in Italy have developed a new method that allows transplants using mismatched marrow. The results of their latest study, reported in The New England Journal of Medicine (October 1998), have raised the hope that one day a donor will be found for virtually every candidate for a bone marrow transplant.

Three Markers Make a Match

Normally, a donor and recipient are considered to be compatible when they are matched for all six immunologic markers on their chromosomes. In the method developed by a team headed by Professor Yair Reisner of Weizmann’s Immunology Department and Dr. Massimo Martelli of Perugia’s Policlinico Monteluce, the donor and recipient need to be matched for only three markers.

Such a partial match is always found between parents and children, and there is a 75% chance of finding it between siblings. Even among extended family members, the chances of finding a partially compatible donor are fairly good.

A key element of the Weizmann-Perugia method is the use of extremely large doses of donor marrow. The donor is treated with hormone injections that release large numbers of stem cells from the bone marrow into the bloodstream. During leukapheresis, stem cells are selectively removed from blood withdrawn from the body, and the remaining blood is reinfused into the donor. The donated stem cells are then “cleansed” to erase the characteristics that contribute to rejection in mismatched transplants.

Method Overcomes Major Obstacles to Mismatched Grafts

In the study, the Perugia-Weizmann team traced the results of dozens of such mismatched transplants performed between 1995 and 1997 in patients with high-risk acute myeloid leukemia or acute lymphoid leukemia.

Of the 43 patients treated, 16 became free of disease. The remaining patients either had a relapse or died of the disease or of transplant-related complications. This result is significant because all of the patients had previously been unresponsive to any other treatment. The results achieved with this method are similar to those achieved with perfectly matched transplants in this category of patients.

According to the researchers, the study shows that their method overcomes the main obstacles limiting the use of mismatched transplants; namely, graft failure and graft-vs-host disease. “Since most patients have a mismatched relative [who can serve as a bone marrow donor], advances in this area will greatly increase the availability of transplants as curative therapy,” they concluded.