title: Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia.
abstract: Immunosuppression with antithymocyte globulin, (methyl)prednisolone, and cyclosporin A is considered the treatment of choice for the patient with aplastic anemia without a donor for standard-risk stem cell transplantation. This consensus is supported by the results of several series, including a randomized German trial. Here we report 11-year results of the latter trial. With stringent response criteria and 4 months as the time to evaluate responses, this analysis confirms the superiority of the cyclosporine regimen regarding the response rate in all patients treated (70% vs 41%, with or without cyclosporine; P =.015) and in patients with severe aplastic anemia (65% vs 31%; P =.011). Patients responded more rapidly after treatment with cyclosporine (median, 60 vs 82 days; P =.019). Most patients treated with cyclosporine needed only one course of immunosuppression, whereas many patients treated without cyclosporine required repeated immunosuppressive treatment. Because of the efficacy of salvage treatment, overall survival was not different between the 2 treatment groups. However, failure-free survival favored the cyclosporine regimen (39% vs 24%; P =.04). The relapse rate, projected at 38% after 11.3 years, was similar between the 2 treatment groups. Remissions were cyclosporine dependent in 26% of the patients responding to a regimen that included cyclosporine. Clonal or malignant diseases developed in 25% of the patients. These data demonstrate that antithymocyte globulin, methylprednisolone, and cyclosporin A are an effective regimen for the treatment of aplastic anemia. However, remissions are unstable, and secondary diseases are common. In contrast to the results of stem cell transplantation, most patients are not cured.
authors.affiliation: Department of Hematology/Oncology, Dr-Horst-Schmidt-Kliniken, Wiesbaden, Germany. n.frickhofen@t-online.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Frickhofen
authors.forename: Hermann
authors.initials: H
authors.lastname: Heimpel
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Kaltwasser
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
mesh_terms: D000741:Anemia, Aplastic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use*; D001772:Blood Cell Count; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D007938:Leukemia / Q000150:complications / Q000453:epidemiology; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000453:epidemiology; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008775:Methylprednisolone