Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors

Bone Marrow Transplant. 2016 Jul;51(7):938-44. doi: 10.1038/bmt.2016.32. Epub 2016 Mar 21.

Abstract

Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes.

MeSH terms

  • Adolescent
  • Adult
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Fanconi Anemia / complications*
  • Fanconi Anemia / mortality
  • Fanconi Anemia / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Retrospective Studies
  • Time Factors
  • Tissue Donors
  • Transplantation Conditioning / methods
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous
  • Whole-Body Irradiation / adverse effects
  • Whole-Body Irradiation / mortality
  • Young Adult

Substances

  • Busulfan