Bone marrow transplants: upping the odds.

For years, bone marrow transplants have tantalized researchers with the promise of a cure for potentially fatal diseases such as leukemia. However, finding a donor with an immune system that closely matches the recipient's has proved a major stumbling block.

Now, researchers have developed a method that may improve the chances of people with leukemia receiving bone marrow transplants from unmatched donors. By transplanting "megadoses" of bone marrow, sometimes as much as 10 times the amount currently used, researchers have found they can reduce the effect of donor-recipient incompatibility

"Such doses appear to be effective because they give donor cells an edge in their competition with recipient cells, thus minimizing the risk of rejection," says Yair Reisner, a biophysicist at the Weizmann Institute of Science in Rehovot, Israel, who developed the new technique with Massimo F. Martelli, a physician at the University of Perugia in Italy.

Reisner, Martelli, and their colleagues report their findings in the Dec. 1 Blood.

A transplant patient receives powerful drugs and radiation therapy to wipe out his or her immune system and diseased bone marrow. The patient then receives healthy bone marrow from a donor. If the transplant takes, the donated marrow will produce new red blood cells, platelets, and white blood cells. Even with a good match, though, transplants can cause severe complications and are done only as a last resort.

Martelli and Reisner treated 17 patients in terminal stages of leukemia with megadoses of bone marrow from unmatched donors. Six of the patients lived for 3 to 16 months after receiving treatment.

To obtain such large amounts of marrow, the researchers give donors hormonal drugs called cytokines to increase the production of blood stem cells, which give rise to all types of red and white blood cells. Stem cells move from the bones into the blood, where the scientists collect 7 to 10 times as many as they normally do when taking marrow directly from the bones.

The researchers then treat the extracted marrow to eliminate T lymphocytes, white blood cells that would otherwise attack the recipient's tissues and cause graft-versus-host disease. The leukemia patients in the study, who had previously undergone drug and radiation therapy, received transfusions of this treated bone marrow.

"By eliminating the need for a very close donor-recipient match," says Reisner, "we hope this new approach will make bone marrow transplants available to all people with leukemia in need of treatment."

However, even if further studies support the effectiveness of this approach, it will take some time before it becomes widely available, he adds.