Israelis and Italians Expand Pool of Bone Marrow Transplant Donors

A team of Israeli and Italian researchers has developed a technique that expands the donor pool for leukemia patients in need of bone marrow transplants.

The method, developed by scientists at the Weizmann Institute of Science in Israel and Perugia University in Italy for obtaining and treating bone marrow, eliminates the need to find a close donor- recipient match.

Leukemia — a group of cancer-like diseases of the blood cells affecting bone marrow and blood- forming tissues and organs — is generally treated with strong chemical and radiation therapies. Bone marrow transplantation, a painful procedure with a limited survival rate, is considered a last resort for terminal cases.

Until now, patients eligible for the radical therapy required a donor whose immune system matched theirs for six genetic markers — three from the father and three from the mother — to avoid rejection and other complications.

These restrictions meant that patients had to find matching donors among their siblings or among the general population, which is even rarer.

Global registries have increased the odds of finding a match, but Jews and members of some other ethnic groups often have a difficult time finding suitable matches among the databases’ millions of names.

Since most patients have relatives who do not match on all six of the markers but who can serve as bone marrow donors using the new technique, “advances in this area will greatly increase the availability of transplants as curative therapy,” professors Yair Reisner of the Weizman Institute and Massimo Martelli of Perugia University conclude in the Oct. 22 issue of the New England Journal of Medicine.

As a result of their work, patients can receive bone marrow transplants from donors matched along only three immunological markers, a partial match shared by parents and children.

Between siblings, there is a 75 percent chance of finding the vital correlation — and finding a partially compatible donor is also possible among extended family members, according to the Weizmann Institute.

Reisner sees big advantages with “mismatched” bone marrow transplants.

“When you don’t have a donor, we can offer you something. You’re not lost,” he said in a telephone interview from Tel Aviv.

And for those waiting to locate an unrelated donor through a registry, he said, “we should be able to offer a solution immediately.”

Bone marrow from unmatched donors carries the danger of triggering residual immunity in the recipient’s blood that may reject the “foreign” marrow. In other cases, the transplanted marrow works against its host in a reverse- rejection.

The Reisner-Martelli method attempts to overcome this problem through “megadoses” of donated stem cells, which are obtained by injecting the donor with special hormones and collected through a process called leukapheresis.

Those cells are “cleaned” of their immune-system agents, giving them a decent chance of being accepted.

The new technique is already being implemented in hospitals in Israel, the United States, Germany and Austria.

Martelli and Reisner, whose collaboration dates to 1985, tracked the progress of 43 patients with acute forms of leukemia who received unmatched transplants between 1995 and 1997.

At the study’s end, the Israeli-Italian team reported results comparable to the outcomes from perfectly matched transplants.

Sixteen of the patients — none of whom had responded to other therapies – – were free of the disease.

The remaining patients either relapsed or had died of the disease or complications from the treatment.

“It’s not a home run,” said Claudio Anasetti, the director of the Unrelated Donor Marrow Transplant Program at the Fred Hutchinson Cancer Research Center in Seattle, one of the world’s foremost facilities. “But it’s a big step towards how to get a transplant without too much toxicity.”