Researchers from the Weizmann Institute and Perugia University in Italy have developed a method that may significantly improve the chances for people with leukemia to receive potentially life-saving bone marrow transplants. Whereas today many leukemia patients fail to find properly matched marrow donors, the new approach -- whose effectiveness still needs to be confirmed in further studies -- may allow them to receive transplants from unmatched individuals, thus making marrow transplantation available to all those in need of the treatment.
The method was developed over the past eight years by Prof. Yair Reisner of the Institute's Department of Membrane Research and Biophysics and Prof. Massimo F. Martelli of the University of Perugia's Policlinico Monteluce in Perugia, Italy.
When the first 17 patients were treated in Italy with their technique, the donor marrow -- drawn from family members who were not entirely compatible with the recipients -- successfully implanted itself in 16 of the cases. Although all the patients had been in terminal stages of leukemia, six were free of the disease when study results were summed up.
Bone marrow transplantation (BMT), a last-resort treatment for leukemia and other disorders, consists of wiping out the patients' immune system and the diseased bone marrow, and infusing them with healthy marrow. Transplanting marrow from unmatched donors has been problematic because, despite the pre-treatment, the patients' residual immune cells may recognize the incompatible transplant as "foreign" and reject it.
The new approach eliminates the requirement for a very close match between donor and recipient by using up to ten times the normal amounts of transplanted marrow. Such "megadoses" appear to be effective because they give transplanted cells an edge in their competition with residual recipient cells, thereby minimizing the risk of rejection.
In addition, the collected marrow is purified using a technique developed by Reisner some ten years ago to enable "bubble" children with severe combined immunodeficiency diseases to undergo BMT. This multi-stage process -- which was also used in treating several victims of the nuclear accident at Chernobyl -- prevents a severe complication known as graft-versus-host disease.
Although the "megadose" method has thus far been tried only in people with leukemia, in the future it may be modified to treat noncancerous blood disorders, such as sickle-cell anemia, and to facilitate organ transplantation.