title: Horse antithymocyte globulin as salvage therapy after rabbit antithymocyte globulin for severe aplastic anemia.
abstract: The effectiveness of salvage therapy for aplastic anemia patients unresponsive to initial rabbit antithymocyte globulin (r-ATG) or cyclophosphamide is not known. We investigated the administration of standard horse ATG (h-ATG) plus cyclosporine (CsA) in patients who were refractory to initial r-ATG/CsA (n = 19) or cyclophosphamide/CsA (n = 6) (registered at clinicaltrials.gov as NCT00944749). The primary endpoint was hematologic response at 3 months and was defined as no longer meeting the criteria for severe aplastic anemia. Of the 19 patients who received r-ATG as initial therapy, 4 (21%) achieved a hematologic response by 3 months, and of the 6 patients who received cyclophosphamide, only 1 (17%) responded by 6 months. Among the responders there were no cases of relapse, and in nonresponders 2 patients evolved to monosomy 7. The overall survival for the cohort at 3 years was 68% (95% CI, 50-91%). These results suggest that only a minority can be successfully salvaged after receiving as first therapy either r-ATG or cyclophosphamide. Although h-ATG may be utilized in the salvage setting, the overall response rate probably will be lower than when h-ATG is used as initial treatment.
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Hematology Service, Oncology Center, Hospital São Jose, Beneficência Portuguesa, São Paulo, Brazil.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scheinberg
authors.forename: Danielle
authors.initials: D
authors.lastname: Townsley
authors.forename: Bogdan
authors.initials: B
authors.lastname: Dumitriu
authors.forename: Priscila
authors.initials: P
authors.lastname: Scheinberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Weinstein
authors.forename: Olga
authors.initials: O
authors.lastname: Rios
authors.forename: Colin O
authors.initials: CO
authors.lastname: Wu
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000473:pathology; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D016572:Cyclosporine; D003520:Cyclophosphamide