Fludarabine- and Low-Dose Cyclophosphamide-Based Conditioning Regimens for Unmanipulated Hematopoietic Cell Transplantation from Unrelated Donors and Matched Siblings in Patients with Fanconi Anemia: Results from the Cbmtr

Hematopoietic cell transplantation (HCT) is the only option to cure hematopoietic complications in Fanconi anemia (FA). We have analyzed 98 unmanipulated HCT from matched siblings and unrelated donors. Overall, the outcomes were favorable, with 100% primary engraftment, 76.7% (66.3-84.3%) probability of three-year overall survival (OS), and 75.9% (65.5-83.5%) of event-free survival (EFS). The incidence of acute graft-versus-host disease (GvHD) was 38.8% (27.1-50.3%) for grade II-IV and 23.4% (11.2-38.2%) for grade III-IV. The incidence of chronic GvHD was 27.7% (13.2-43.7%) for all grades and 13.0% (1.4-34.1%) for moderate-to-severe disease. Comparing different conditioning regimens, patients conditioned with fludarabine (Flu) and low-dose cyclophosphamide (Cy) achieved 100% probabilities of OS and EFS, which was superior to those with additional busulfan (Bu) or irradiation (P=.024 and .020, respectively). No significant difference was found in the incidences of GvHD across conditioning regimens. We demonstrated that high-dose Bu (> 6.4 mg/kg vs. ≤ 6.4 mg/kg) was associated with an increased risk of death [hazard ratio (HR)=6.705 (2.384-18.855), P<.001] and events [HR=5.434 (2.060-14.334), P=.001]. In conclusion, unmanipulated HCT from matched siblings and unrelated donors achieved favorable engraftment, OS, and EFS in FA patients. Our data suggested that conditioning regimens based on Flu and low-dose Cy provided excellent survival.

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