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 Weizmanns Immunology Department and Dr. Massimo
Martelli of Perugias 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selectively removed from blood withdrawn from the body, and the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