Bone marrow transplantation for severe aplastic anemia

Allogeneic marrow transplantation from an HLA-identical sibling has proven to be an effective treatment for severe aplastic anemia with restoration of normal hematopoiesis and long-term survival in 70-80% of recipients. Results are related to patient age, with improved survival in younger patients. Marrow transplantation from HLA nonidentical family and unrelated donors has been less successful and is the focus of ongoing clinical research. Graft rejection and graft-versus-host disease (GVHD) remain major problems. A number of pre- and post-transplant immunosuppressive regimens to prevent these complications continue to be studied. The risk of graft rejection is increased in patients who have been transfused before transplant, whereas the risk is decreased with the infusion of larger numbers of transplanted marrow cells. The incidence of graft rejection is 10-32% when cyclophosphamide is used alone as the pretransplant conditioning regimen. The addition of donor buffy coat cells and whole body or limited field radiation have reduced the rate of graft rejection, but increased the incidence of complications such as chronic GVHD and secondary malignancies. GVHD is an immune disorder caused by incompatibility between donor and recipient for histocompatibility antigens. Approximately 18-40% of patients experience moderate to severe acute GVHD. Previous pregnancy in female donors and increasing age of the patient are factors predictive of its development. Methotrexate and cyclosporin have been used most frequently as prophylactic immunosuppressive agents; various combinations of these drugs and prednisone are being evaluated. Symptomatic chronic GVHD occurs in approximately 25% of recipients. Cyclosporin and prednisone are used as treatment for this disorder.