title: Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors.
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.
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Anur
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Friedman
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sklar
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Oeffinger
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Castiel
authors.affiliation: Department of Psychiatry, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kearney
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: B
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Prockop
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Scaradavou
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kobos
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Curran
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ruggiero
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zakak
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Reilly
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Pediatrics, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.
authors.forename: F
authors.initials: F
authors.lastname: Boulad
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000150:complications* / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000401:mortality; D055815:Young Adult
chemical_list: D002066:Busulfan