Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations - PubMed (original) (raw)

Review

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

Christen L Ebens et al. Expert Rev Hematol. 2017 Jan.

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.

Keywords: Fanconi anemia; bone marrow failure; hematopoietic cell transplantation; late effects; survivorship.

PubMed Disclaimer

Figures

Figure 1

Figure 1

References

    1. Auerbach AD. Fanconi anemia and its diagnosis. Mutat Res. 2009;668(1–2):4–10. -PMC -PubMed
    1. Dong H, Nebert DW, Bruford EA, et al. Update of the human and mouse Fanconi anemia genes. Hum Genomics. 2015;9(1):32. Summary of the first 19 human gene mutations associated with FA, their murine orthologs, and an evolutionary perspective on the role of these gene mutations. FA associated gene mutations continue to be discovered as demonstrated in references [3] and [4] -PMC -PubMed
    1. Park JY, Virts EL, Jankowska A, et al. Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene. J Med Genet. 2016;53(10):672–80. -PMC -PubMed
    1. Bluteau D, Masliah-Planchon J, Clairmont C, et al. Biallelic inactivation of REV7 is associated with Fanconi anemia. J Clin Invest. 2016;126(9):3580–4. -PMC -PubMed
    1. Butturini A, Gale RP, Verlander PC, et al. Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Blood. 1994;84(5):1650–5. -PubMed

Publication types

MeSH terms

LinkOut - more resources