title: Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations.
abstract: Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.
authors.affiliation: a Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics , University of Minnesota Medical School , Minneapolis , MN , USA.
authors.forename: Christen L
authors.initials: CL
authors.lastname: Ebens
authors.affiliation: a Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics , University of Minnesota Medical School , Minneapolis , MN , USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: a Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics , University of Minnesota Medical School , Minneapolis , MN , USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
mesh_terms: D003131:Combined Modality Therapy; D004260:DNA Repair; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D011300:Preoperative Care; D012074:Remission Induction; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
keywords: Fanconi anemia; bone marrow failure; hematopoietic cell transplantation; late effects; survivorship