title: Cyclophosphamide and other new agents for the treatment of severe aplastic anemia.
abstract: Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed.
authors.affiliation: Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Tisdale
authors.forename: D E
authors.initials: DE
authors.lastname: Dunn
authors.forename: J
authors.initials: J
authors.lastname: Maciejewski
mesh_terms: D000741:Anemia, Aplastic / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus