title: Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party.
abstract: Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.
authors.affiliation: Department of Haematological Medicine, King's College Hospital/King's College London, London, United Kingdom. judith.marsh@nhs.net
authors.forename: Judith C
authors.initials: JC
authors.lastname: Marsh
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Risitano
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Passweg
authors.forename: Sally B
authors.initials: SB
authors.lastname: Killick
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Warren
authors.forename: Theodora
authors.initials: T
authors.lastname: Foukaneli
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.forename: H A
authors.initials: HA
authors.lastname: Al-Zahrani
authors.forename: Britta
authors.initials: B
authors.lastname: Höchsmann
authors.forename: Philip
authors.initials: P
authors.lastname: Schafhausen
authors.forename: Alexander
authors.initials: A
authors.lastname: Roth
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brummendorf
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Rosi
authors.initials: R
authors.lastname: Oneto
authors.forename: Philip
authors.initials: P
authors.lastname: Sedgwick
authors.forename: Alain
authors.initials: A
authors.lastname: Barrois
authors.forename: Shahram
authors.initials: S
authors.lastname: Kordasti
authors.forename: Modupe O
authors.initials: MO
authors.lastname: Elebute
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy*; D000818:Animals; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006736:Horses; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011817:Rabbits; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine