Presently, only 25% of people who need a bone marrow transplant have a compatible sibling donor. We are in the process of evaluating strategies for mismatched stem cell transplantation that, if are successful, will mean virtually every patient who needs a donor will have one. With our tolerance induction strategies, transplant recipients can be freed from a lifelong regimen of powerful immunosuppressive drugs.

There are two notable areas where we have achieved encouraging successes:

• Non-myeloablative mini-stem cell transplants - Typically, bone marrow transplants use high doses of chemotherapy and radiation to wipe out the recipient's immune system - a procedure that is not without serious toxicity. With non-myeloablative ("mini") transplants, there is less radiation and chemotherapy used, for the goal is not to destroy the recipient's immune system, but rather to suppress the T cells, which fight foreign substances, and then to gradually introduce the donor's immune system. This mixed chimerism, or blended immune system, is balanced to prevent both rejection of the bone marrow (and solid organ, when a combined transplant is performed) and the development of graft-versus-host disease, in which the donor's marrow attacks the recipient's body. Our specialists have successfully used mixed chimerism to treat patients with a variety of advanced hematologic malignancies including aggressive lymphoma that has been highly resistant to conventional treatments.
• Simultaneous kidney and bone marrow transplants - Patients who have multiple myeloma (a form of bone marrow cancer) can also have kidney failure and need dialysis in order to keep them alive. Because of the kidney failure, these patients are not likely to survive the full bone marrow transplant usually performed to treat multiple myeloma. By transplanting bone marrow at the same time the kidney transplant is done, we have been able to achieve tolerance and to treat the myeloma. We are the first facility in the world to perform this operation in six different patients. Tolerance induction has been successfully achieved in most of the cases, and sustained remissions of the bone marrow cancer have also been observed. The successes in these cases have led to a National Institutes of Health funded study at Mass General to see if mixed chimerism might work to induce similar tolerance of transplanted organs when no underlying malignancy is present.
• HLA typing of the patient and potential family bone marrow donors is a very important step in the pre-transplant testing phase. It helps to determine which family member is the most closely matched to the patient and would be the best marrow donor. Our Histocompatibility Laboratory coordinates the collection and transfer of blood specimens to the hospital from the prospective family members. This assures that the HLA testing is performed in the most reliable, uniform and expeditious fashion.

The Bone Marrow Transplant Program at Massachusetts General Hospital was founded in 1993 with the mission of developing new strategies for successfully performing HLA (human leukocyte antigens - inherited markers found on the surface of white blood cells) mismatched donor bone marrow transplantation. We have concentrated on inducing organ transplant tolerance and reducing the toxicity of bone marrow transplantation. By working collaboratively with the Transplantation Biology Research Center (TBRC) , a multidisciplinary research group focused on transplantation immunology, our bone marrow transplant team has a very strong translational program of pre-clinical models that lead to innovative clinical trials. As a result, we have made major advances in the field of transplantation and are able to offer our patients innovative transplant strategies for patients with malignancies and those needing both a bone marrow and kidney transplant. We have had a leading role in the development of HLA mismatched transplant strategies and are currently conducting clinical trials that if successful, will revolutionize the field of organ transplantation by inducing tolerance across HLA barriers.