Advances in stem cell transplantation for Fanconi anemia

INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only available curative treatment option for hematologic manifestations of Fanconi anemia (FA), which include bone marrow failure and hematological malignancies. Outcomes after allo-HCT have improved significantly over the last 30 years by optimizing preparative regimens, graft-versus-host-disease (GvHD) prophylaxis, and supportive care. Nevertheless, indications for transplant should be carefully weighed, based on a thorough evaluation of risks and benefits, as this procedure has intrinsic morbidity and mortality and may increase the risk and accelerate the onset of late malignancies and FA-related complications. AREAS COVERED: This review, following a thorough Medline search of the pertinent published studies, reports the most recent data on HCT in FA, focusing on HCT strategies, post-transplant follow-up, and impact of allo-HCT on FA-associated late effects. EXPERT OPINION: While we continue to generate evidence to determine the optimal candidates, timing, and strategies for HCT in FA patients, we must also consider the implications for future treatment modalities like gene therapy/gene editing. The primary objective of all strategies must be to mitigate - or at the very least, not exacerbate - the risk of long-term complications that remain a leading cause of the unacceptably high mortality rate in FA.