BONE-MARROW TRANSPLANTATION FOR APLASTIC-ANEMIA

The increased survival of aplastic anemia patients treated by human leukocyte antigens (HLA)-identical marrow transplants is due in part to a decrease in the incidence of graft rejection. The decrease in rejection, in turn, results from the more judicious use of transfusions before transplant, the removal of sensitizing white blood cells from transfusion products, and improvements in the immunosuppressive conditioning programs used to prepare patients for transplant. In regards to the latter, radiation-based programs have been effective, although a cyclophosphamide/antithymocyte globulin program begins to look impressive with only one rejection among 33 patients transplanted. In regards to transfusions before transplant, in vitro radiation of all blood products may further reduce the risk of sensitization to minor histocompatibility antigens in the future. The incidence and severity of acute graft-versus-host disease (GvHD) have declined with the use of the methotrexate/cyclosporine regimen, and this has also contributed to improved survival. Chronic GvHD is difficult to treat and future emphasis should be on prevention rather than on treatment. Whether an extended course of cyclosporine beyond 6 mo after transplant will reduce the risk of chronic GvHD is under study. As more and more patients become long-term survivors, problems from long-term sequelae from the conditioning programs and from postgrafting immunosuppression must be considered, in particular secondary malignancies. Perhaps less toxic conditioning programs can be designed. Because of the higher likelihood of causing secondary cancer, possible deleterious effects on growth and development for pediatric patients, and the problem of sterility, radiation-based regimens should not be used in HLA-identical recipients.