title: Alternative donor hematopoietic cell transplantation for Fanconi anemia.
abstract: Historically, alternative donor hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) patients resulted in excessive morbidity and mortality. To improve outcomes, we made sequential changes to the HCT conditioning regimen. A total of 130 FA patients (median age, 9.0 years; range, 1-48) underwent alternative donor HCT at the University of Minnesota between 1995 and 2012. All patients received cyclophosphamide (CY), single fraction total body irradiation (TBI), and antithymocyte globulin (ATG) with or without fludarabine (FLU), followed by T-cell-depleted bone marrow or unmanipulated umbilical cord blood transplantation. The addition of FLU enhanced engraftment 3-fold. The incidence of grades 2-4 acute and chronic graft-versus-host disease was 20% and 10%, respectively. Severe toxicity was highest in patients >10 years of age or those with a history of opportunistic infections or transfusions before HCT. Mortality was lowest in patients without a history of opportunistic infection or transfusions and who received conditioning with TBI 300 cGy, CY, FLU, and ATG. These patients had a probability of survival of 94% at 5 years. Alternative donor HCT is now associated with excellent survival for patients without prior opportunistic infections or transfusions and should be considered for all FA patients after the onset of marrow failure. These studies were registered at http://www.clinicaltrials.gov as NCT00005898, NCT00167206, and NCT00352976.
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: Blood and Marrow Transplant Program, Biostatistics and Informatics Core, Masonic Cancer Center.
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.affiliation: Department of Medicine.
authors.forename: Jo-Anne H
authors.initials: JA
authors.lastname: Young
authors.affiliation: Department of Therapeutic Radiology, and.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Dusenbery
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine.
authors.forename: Arne
authors.initials: A
authors.lastname: Slungaard
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN.
authors.forename: Heather
authors.initials: H
authors.lastname: Zierhut
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics.
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000453:epidemiology; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
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