Allogeneic bone marrow transplantation: procedures and complications

Bone marrow transplantation (BMT) is discussed in terms of immunology, procedures, and complications and their treatment. Any patient with a disorder of the hematopoietic or immune system or a disease in which a transferable hematopoietic cell can supply a missing enzyme is a candidate for BMT. A priority in allogeneic BMT is the identification of a compatible donor through matching of human lymphocyte antigens (HLAs). The greater the disparity in HLAs, the greater the chance of rejection. The ideal donor is a monozygotic twin or an HLA-matched sibling, but only 30% of patients have such a donor. Before receiving the bone marrow infusion, patients must be conditioned to create space in the marrow for donor cells, suppress the immune system, and eradicate any tumor in patients with malignancies. Conditioning is achieved by the combination of total body irradiation and cyclophosphamide treatment; busulfan, etoposide, and cytarabine have also been used. For patients given unmanipulated marrow, the number of nucleated cells infused is about 3 X 10(8) per kilogram. Signs of engraftment are usually seen 14-21 days later. Toxic effects related to conditioning appear during this period and include infection, gastroenteritis, mucositis, and congestive heart failure. The most serious complication is graft-versus-host disease (GVHD), which can affect multiple organ systems. Prednisone, methylprednisolone, methotrexate, antithymocyte globulin, and cyclosporine have been used in an effort to prevent or treat GVHD. Bone marrow transplantation offers the chance of long-term survival to many patients with terminal disease, but associated morbidity and mortality rates remain high. Research is needed to address the problems of infection, leukemic relapse, and GVHD and the difficulty in obtaining and matching donors.