title: Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party.
abstract: We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (<or=14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n=3), graft failure (n=2), Epstein-Barr virus lymphoma (n=2) and hemorrhage (n=2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults.
authors.affiliation: Department of Hematology 2, Azienda Ospedaliera Universitaria San Martino, Largo Benzi, Genova, Italy. andrea.bacigalupo@hsanmartino.it
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: E
authors.initials: E
authors.lastname: Lanino
authors.forename: J
authors.initials: J
authors.lastname: Marsh
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: S
authors.initials: S
authors.lastname: Maury
authors.forename: A
authors.initials: A
authors.lastname: Prete
authors.forename: A
authors.initials: A
authors.lastname: Locasciulli
authors.forename: S
authors.initials: S
authors.lastname: Cesaro
authors.forename: J
authors.initials: J
authors.lastname: Passweg
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D006801:Humans; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine