title: Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia.
abstract: Bone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-cell-depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell-depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.
authors.affiliation: Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN 55455, USA. wagne002@umn.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005199:Fanconi Anemia / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D009504:Neutrophils / Q000166:cytology; D011336:Probability; D011379:Prognosis; D015996:Survival Rate; D014019:Tissue Donors