title: Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation.
abstract: Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429)
authors.affiliation: Department of Hematology, Bone Marrow Transplant Unit, Hôpital Saint-Louis, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Guardiola
authors.forename: R
authors.initials: R
authors.lastname: Pasquini
authors.forename: I
authors.initials: I
authors.lastname: Dokal
authors.forename: J J
authors.initials: JJ
authors.lastname: Ortega
authors.forename: M
authors.initials: M
authors.lastname: van Weel-Sipman
authors.forename: J C
authors.initials: JC
authors.lastname: Marsh
authors.forename: S E
authors.initials: SE
authors.lastname: Ball
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: C
authors.initials: C
authors.lastname: Vermylen
authors.forename: R
authors.initials: R
authors.lastname: Skinner
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: R
authors.initials: R
authors.lastname: Miniero
authors.forename: P J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: G
authors.initials: G
authors.lastname: Souillet
authors.forename: M
authors.initials: M
authors.lastname: Michallet
authors.forename: A N
authors.initials: AN
authors.lastname: Bekassy
authors.forename: G
authors.initials: G
authors.lastname: Krivan
authors.forename: P
authors.initials: P
authors.lastname: Di Bartolomeo
authors.forename: C
authors.initials: C
authors.lastname: Heilmann
authors.forename: L
authors.initials: L
authors.lastname: Zanesco
authors.forename: J Y
authors.initials: JY
authors.lastname: Cahn
authors.forename: W
authors.initials: W
authors.lastname: Arcese
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005199:Fanconi Anemia / Q000401:mortality / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome