Drug May Allow Unmatched Transplants of Bone Marrow

A new, highly selective immune-suppressing drug may allow cancer patients to receive bone marrow transplants from poorly matched donors without suffering life-threatening complications.

The drug suppresses only that part of the immune system that causes the complications. Doctors say this could allow patients to receive marrow transplants without drugs that broadly suppress the body’s immune defenses. These drugs raise the risk of infections.

In today’s issue of the New England Journal of Medicine, researchers reported that the approach worked surprisingly well in the first experimental use. “This is starting to crack open the door on a new way of manipulating the immune system,” said Dr. Eva C. Guinan of Boston’s Dana-Farber Cancer Institute, where the approach was developed.

Bone marrow manufactures blood cells and sometimes must be replaced because of leukemia and other marrow cancers. To minimize complications, doctors seek a close genetic match with the donor. Guinan said the treatment, CTLA4-Ig, could eliminate the need for near-perfect matches.

CTLA4-Ig blocks development of graft versus host disease. The drug stops only the cells that cause the disease, leaving intact the immune function of the new marrow.

Doctors tested the approach on 12 young patients with advanced leukemia for whom only poorly matched marrow was available. No severe graft versus host disease occurred. Five have survived for five to 29 months, while the rest died after treatment complications and cancer relapse.

Journal Deputy Editor Robert S. Schwartz, who helped pioneer immune suppression for organ transplants in the 1950s, called the results impressive. However, in an editorial, he cautioned that this “must be balanced against the small number of patients, the high death rate and the lack of information about immunologic reconstitution in the survivors.”