title: Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial.
abstract: A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)
authors.affiliation: Dipartimento di Scienze Pediatriche, Università di Pavia, IRCCS Policlinico San Matteo, Pavia, Italy. f.locatelli@smatteo.pv.it
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: B
authors.initials: B
authors.lastname: Bruno
authors.forename: M
authors.initials: M
authors.lastname: Zecca
authors.forename: M T
authors.initials: MT
authors.lastname: Van-Lint
authors.forename: S
authors.initials: S
authors.lastname: McCann
authors.forename: W
authors.initials: W
authors.lastname: Arcese
authors.forename: S
authors.initials: S
authors.lastname: Dallorso
authors.forename: P
authors.initials: P
authors.lastname: Di Bartolomeo
authors.forename: F
authors.initials: F
authors.lastname: Fagioli
authors.forename: A
authors.initials: A
authors.lastname: Locasciulli
authors.forename: M
authors.initials: M
authors.lastname: Lawler
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000401:mortality / Q000628:therapy*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009679:Nuclear Family; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate