"It really has been an all-or-nothing situation, with patients facing two hazards," says Spitzer. "If the transplanted marrow doesn't take or is rejected, patients are left with no immune system. When patients receive transplants from less closely matched donors, they risk graft-versus-host disease, a life-threating complication that develops when the donor marrow attacks the recipient's tissues."

Mixed chimerism represents a balanced state in which elements from both the donor and recipient immune systems successfully coexist. It was originally achieved in animal studies in the laboratory of David Sachs, M.D., director of the MGH-TBRC and a co-author of the Lancet paper. Mixed chimerism now is being extensively studied by Sachs and his colleagues for its potential to allow transplantation of organs without long-term use of immunosuppressive drugs.

Sykes developed the concept of applying the mixed chimerism work to treatment-resistant lymphomas. She made the original observation in animal studies that administration of donor lymphocytes (white blood cells) to mixed chimeras could induce an anti-tumor effect without causing severe graft-versus-host disease. Her team collaborated with Spitzer's bone marrow transplant group to develop a strategy for replicating this response in human recipients of mismatched bone marrow transplants who received a milder course of pretransplant chemotherapy, combined with monoclonal antibodies against T cells, the specific type of lymphocyte involved in rejecting transplanted tissues.

The current study is the first to achieve intentional mixed chimerism in human patients receiving mismatched marrow transplants without intensive pretransplant preparation. The technique was applied in five patients with advanced, treatment-
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Contact: Susan McGreevey
smcgreevey@partners.org
617 724-2764
Massachusetts General Hospital
21-May-1999