title: Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocyte colony-stimulating factor in patients with aplastic anaemia and myelodysplastic syndrome.
abstract: This report describes the final results of a Phase II clinical trial investigating the efficacy of rabbit antithymocyte globulin (rATG), ciclosporin, steroids, and granulocyte colony-stimulating factor (GCSF) in patients with untreated aplastic anaemia (AA), or low to intermediate-risk and hypocellular myelodysplastic syndrome (MDS). We treated 24 patients each with AA and MDS with rATG (3·5 mg/kg/d × 5; reduced to 2·5 mg/kg/d × 5 in patients with MDS ≥ 55 years), ciclosporin (5 mg/kg orally daily × 6 months), steroids (1 mg/kg daily, tapered off over 1 month), and GCSF. The overall response rate in AA patients was 64% compared to 25% in MDS patients. The median time to response was 3 months in AA patients and 4 months in MDS patients. Pretreatment clinical characteristics, such as age, sex, blood counts, cellularity, cytogenetics, or HLA-DR15 status, did not predict for response. Response to therapy, however, predicted for improved overall survival (OS), with a 3-year OS of 89% vs. 43% in responders versus non-responders, respectively (P < 0·001). Infusion reactions occurred in about half the patients and were manageable. Myelosuppression, elevation in liver enzymes, and infections were common. The early mortality in MDS patients was 13% vs. 0% in AA patients.
authors.affiliation: Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. tkadia@mdanderson.org
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Sergerrne
authors.initials: S
authors.lastname: York
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Mark
authors.initials: M
authors.lastname: Brandt
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000188:drug therapy*; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D008775:Methylprednisolone