title: Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution.
abstract: We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51%) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at approximately 8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with < 25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.
authors.affiliation: Serviço de Transplante de Medula Ossea, Hospital de Clínicas, Universidade Federal do Paraná, Rua General Carneiro 181, 80060-900 Curitiba, PR, Brazil. crdemedeiros@terra.com.br
authors.forename: C R
authors.initials: CR
authors.lastname: de Medeiros
authors.forename: M A
authors.initials: MA
authors.lastname: Bitencourt
authors.forename: J
authors.initials: J
authors.lastname: Zanis-Neto
authors.forename: E C P
authors.initials: EC
authors.lastname: Maluf
authors.forename: D S
authors.initials: DS
authors.lastname: Carvalho
authors.forename: C S
authors.initials: CS
authors.lastname: Bonfim
authors.forename: V M
authors.initials: VM
authors.lastname: Funke
authors.forename: D C
authors.initials: DC
authors.lastname: Setubal
authors.forename: N
authors.initials: N
authors.lastname: Farah
authors.forename: R
authors.initials: R
authors.lastname: Pasquini
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide