An MGH research team has shown that it is possible to transplant bone marrow from mismatched human donors without the usual pre-transplant destruction of the patient's own bone marrow. The scientists from the MGH Bone Marrow Transplant Program and the Transplantation Biology Research Center (TBRC) successfully induced a state of mixed chimerism — in which the immune systems from both donor and recipient are blended — in four patients with aggressive non-Hodgkins lymphomas that resisted other treatment methods. Two of those patients have achieved long-term remission without significant graft-versus-host disease, a dangerous complication of bone marrow transplantation. The report appears in the May 22 issue of The Lancet.

"This proof-of-principle study has shown that we can achieve a lasting combination of donor and recipient immune systems without the kind of toxic treatment usually used to wipe out the recipient's bone marrow," says Megan Sykes, MD, of the TBRC, the paper's lead author. "We are intrigued by the powerful anti-tumor effect observed in several patients."

Thomas Spitzer, MD, director of the Bone Marrow Transplant Program and principal investigator of the study described in the Lancet paper, adds, "While it's much too early to say whether this approach will benefit and be safe for all patients with advanced blood cell cancers, we're very encouraged by the results we've seen."

Mixed chimerism — a balanced state in which elements from both the donor and recipient immune systems successfully coexist — was originally achieved in animal studies in the laboratory of David Sachs, MD, director of the MGH's TBRC. Sykes developed the concept of applying the mixed chimerism work to treatment-resistant lymphomas. 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.

Along with Sachs, co-authors of the report are Frederic Preffer, PhD; Steven McAfee, MD; Susan Saidman, PhD; Dina Weymouth; David Andrews, MD; Christine Colby, PharmD; and Robert Sackstein, MD.