All of the patients Sykes described had developed kidney failure as a result of multiple myeloma, a cancer of the bone marrow. Traditionally, such patients had no good treatment options. They were not eligible for kidney transplantation because of their cancer, and the kidney failure made them unable to tolerate the toxic aspects of standard bone marrow transplantation, which has been used for some myeloma patients. For many years Sykes and her colleagues at MGH -- along with collaborators at BioTransplant Incorporated of Charlestown, Mass. -- have been studying mixed chimerism and its application for both treatment of blood-cell cancers and for inducing tolerance, a state in which an organ recipient's immune system no longer recognizes the donor's tissues as foreign.
MGH TBRC researchers and Thomas R. Spitzer, MD, director of the MGH Bone Marrow Transplant Unit, developed a less toxic bone marrow transplantation protocol in which the recipient's immune system is only suppressed instead of totally destroyed. Utilizing this approach, called non-myeloablative bone marrow transplantation, the first patient received a combined transplant in September 1998. As reported the following year, the patient's immunosuppression was tapered off after the procedure and discontinued on the 73rd post-transplant day. Today the patient remains in remission from cancer and free of rejection of the transplanted kidney. The second patient was transplanted in August 2000 and also remains in remission and rejection-free.
The additional patients described by Sykes are the first treated under a multi-institutional study sponsored by the Immune Tolerance Network (ITN) and funded by the National Institute of Allergy and Infectious Disease, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation. The third, transplanted more than a year ago, remains in remission from myeloma, and although continuing to receive low-dose immunosuppression because of mild graft-versus-host disease, has had no episodes of kidney rejection. The fourth patient now is 70 days post-transplant and has discontinued immunosuppression. Led by Sykes and A. Benedict Cosimi, MD, director of the MGH Transplant Unit, the ITN-sponsored study will eventually enroll 10 patients with both kidney failure and multiple myleoma at the MGH and two collaborating centers.
"Our results demonstrate that long-lasting tolerance can be induced with non-myeloablative bone marrow transplantation," says Sykes, who also is professor of Surgery and Medicine (Immunology) at Harvard Medical School. "Our group also is starting a new study of the induction of mixed chimerism for tolerance in patients without cancer who need kidney tranplants." That investigation, also sponsored by the Immune Tolerance Network, is being led by David Sachs, MD, director of the MGH TBRC, and Cosimi.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine.
In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.