title: HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide.
abstract: Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.
authors.affiliation: Bone Marrow Transplantation Service, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: Carmem M
authors.initials: CM
authors.lastname: Bonfim
authors.forename: Carlos R
authors.initials: CR
authors.lastname: de Medeiros
authors.forename: Marco A
authors.initials: MA
authors.lastname: Bitencourt
authors.forename: José
authors.initials: J
authors.lastname: Zanis-Neto
authors.forename: Vaneuza A M
authors.initials: VA
authors.lastname: Funke
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Setubal
authors.forename: Jefferson
authors.initials: J
authors.lastname: Ruiz
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D033001:Directed Tissue Donation; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D016019:Survival Analysis; D017741:Survivors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D019653:Myeloablative Agonists; D003520:Cyclophosphamide