title: Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.
abstract: Acute leukaemia or advanced myelodysplastic syndrome (MDS ≥ 5% blasts) in Fanconi anaemia (FA) patients is associated with a poor prognosis. We report 21 FA patients with acute leukaemia or advanced MDS who underwent haematopoietic cell transplantation (HCT) at the University of Minnesota between 1988 and 2011. Six patients had biallelic BRCA2 mutations. Eight patients received pre-transplant cytoreduction, with 3 achieving complete remission. HCT donor source included human leucocyte antigen-matched sibling (n = 2) or alternative donors (n = 19). Neutrophil engraftment was 95% for the entire cohort, and the incidence of acute graft-versus-host disease was 19%. 5-year overall survival (OS) was 33%, with a relapse rate of 24%, with similar OS in patients with biallelic BRCA2 mutations. Our study supports the use of HCT in the treatment of FA patients with acute leukaemia or advanced MDS, however, the role of chemotherapy prior to HCT remains unclear for this population. FA patients with biallelic BRCA2 are unique and may benefit from higher dose chemotherapy relative to other complementation groups.
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mitchell
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Betsy
authors.initials: B
authors.lastname: Hirsch
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.forename: Heather
authors.initials: H
authors.lastname: Zierhut
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005199:Fanconi Anemia / Q000097:blood / Q000601:surgery*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000097:blood / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000601:surgery*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: Fanconi anaemia; leukaemia; myelodysplastic syndrome; transplantation