Life-Saving Discrepancy: Study Shows Effectiveness of Mismatched Bone Marrow Transplants


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REHOVOT, Israel  October 22, 1998  For many leukemia sufferers, bone marrow transplantation is their only hope. Unfortunately, in about 40 percent of terminal cases, patients fail to find a perfectly matched donor among relatives or in any of the donor registries.

Now, scientists from Israel's Weizmann Institute of Science and Perugia University in Italy have shown that thanks to a method they developed, transplants using mismatched marrow can be as effective as those in which the donor and recipient are fully matched. The results of their latest study, reported in the October 22 issue of the New England Journal of Medicine, have raised hopes that one day a donor will be found for virtually every candidate for a bone marrow transplant.

Normally, a donor and recipient are considered compatible when they are matched for all six immunological markers on their chromosomes  three inherited from the mother and three from the father. In the method developed by a team headed by Prof. Yair Reisner of Weizmann's Immunology Department and Prof. Massimo Martelli of Perugia's Policlinico Monteluce, the donor and the 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-percent chance of finding it between siblings. Even among the extended family, 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 that literally overwhelm the recipient's rejection mechanism. The donor is treated with hormone injections that release large numbers of stem cells from the bone marrow into the bloodstream. In a procedure known as leukapheresis, the stem cells are selectively removed from blood withdrawn from the body, and the remaining blood is re-infused into the donor.

In another crucial step, donated stem cells are then "cleansed" to erase the characteristics that contribute to rejection in mismatched transplants.

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

Of the 43 patients treated, 12 (28 percent) were free of disease when the study results were summed up, 8 to 30 months after transplantation (a median follow-up of 18 months). To appreciate this figure, one must keep in mind that all patients had failed to respond to any other treatment, and without a transplant would have certainly died. The rest of the patients were alive but had a relapse of leukemia, or had died of the disease or of transplant-related complications.

These results are similar to the success rate obtained in this category of patients with perfectly matched transplants from unrelated donors.

According to the scientists, the study shows that their method overcomes the main obstacles limiting the use of mismatched transplants  namely, graft failure and an adverse immunological reaction called graft-versus-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," the researchers conclude in their report.

Several hospitals in Israel, Germany, Austria and the United States have begun to introduce the Perugia-Weizmann transplantation method.

Prof. Reisner holds the Henry H. Drake Professorial Chair in Immunology at the Weizmann Institute. This research was funded in part by Rowland Schaefer, Miami, Florida; the Pauline Fried Estate, Los Angeles, California; the Concern Foundation, Los Angeles, California; the Israel Academy of Sciences and Humanities; Comitato per la Vita "Daniele Chianelli"; Associazione Italiana Ricerche sul Cancro (AIRC); Associazione Italiana Leucemie e Linfomi (AIL), and Istituto Superiore di Sanita, Italy-USA Program on Therapy of Tumors.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.