title: Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia.
abstract: Eighteen consecutive patients aged 5.5-24 years with Fanconi anaemia and diagnoses of aplastic anaemia (n = 8), myelodysplastic syndrome (n = 4), acute myeloid leukaemia (n = 6), received allogeneic haematopoietic stem cell transplants from alternative donors. All patients had been transfused, 13 had previously been treated with androgens and 14 had a history of infection. Donors were related human leucocyte antigen (HLA) mismatched for eight patients, unrelated HLA mismatched for seven patients and unrelated HLA matched for three patients. Cytoreduction included single dose total body irradiation (450 cGy), fludarabine (150 mg/m(2)) and cyclophosphamide (40 mg/kg). Immunosuppression included antithymocyte globulin and tacrolimus. Grafts were granulocyte colony-stimulating factor-mobilized, CD34+ T-cell-depleted peripheral blood stem cells in 15 patients and T-cell-depleted marrows in three. All 18 patients engrafted with 100% donor chimaerism; only one patient developed graft-versus-host disease (GVHD). With a median follow-up of 4.2 years, 13/18 patients were alive, 12 of these were disease-free. Five-year overall survival and disease-free survival were 72.2% and 66.6% respectively. Immune reconstitution was achieved at approximately 6 months post-transplant for most patients. These are encouraging results of T-cell-depleted transplants from alternative donors using fludarabine-based cytoreduction in 18 high-risk patients with Fanconi anaemia, with no evidence of rejection and minimal GVHD.
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Sonali
authors.initials: S
authors.lastname: Chaudhury
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Susan E
authors.initials: SE
authors.lastname: Prockop
authors.forename: Andromachi
authors.initials: A
authors.lastname: Scaradavou
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wolden
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D014740:Vidarabine; C024352:fludarabine