Pre-treating histoincompatible donor bone marrow reduces risk of GVHD.

Pre-treating histoincompatible donor bone marrow with a highly selective immunosuppressant improves engraftment rates and reduces the risk of graft-versus-host disease (GVHD), Boston, Mass. researchers reported in the June 3rd issue of The New England Journal of Medicine.

The pretreatment agent, called CTLA4-lg, selectively inhibits activation of T-cells--the cells that prevent engraftment and promote GVHD--leaving intact the rest of the immune function of the newly transferred marrow. CTLA4-lg pretreatment could make more transplants possible by eliminating the need for near-perfect matches between donors and recipients, said Eva Guinan, MD of the Dana-Farber Cancer Institute and colleagues there and at Harvard Medical School. It also could make transplants safer by potentially making unnecessary lifelong nonspecific immunosuppression, which inhibits the body's immune defenses and increases the risk of infections and cancer.

The researchers tested the technique in 12 youngsters terminally ill with advanced leukemia for whom only poorly matched marrow was available. The treated haploidentical bone marrow engrafted in all 11 of the recipients who could be evaluated, and none developed severe GVHD. Five of the children have survived from 5-29 months, the remaining 7 died of treatment complications (infection, hemorrhage, multiorgan failure) or cancer relapse.

"[CTLA4-lg] is starting to crack open the door on a new way of manipulating the immune system," said Guinan, who predicts the treatment may also make it easier to transplant hearts, kidneys, and other organs.

Commenting on the findings in the same journal issue, deputy editor Robert Schwartz, MD said that the "positive results are impressive, but they must be balanced against the small number of patients, the high death rate, and the lack of information about immunologic reconstitution in the survivors."

Schwartz noted that the procedure is unlikely to be widely utilized "because of the technical means and financial support it requires." He agreed, however, that using the body's own mechanisms for controlling the immune response "...could be a far better solution to the problem of allograft rejection (and even to the treatment of autoimmune diseases) than nonspecific immunosuppressive drugs."