Reduced-Toxicity Conditioning With Fludarabine, Once-Daily Intravenous Busulfan, and Antithymocyte Globulins Prior to Allogeneic Stem Cell Transplantation: Results of a Multicenter Prospective Phase 2 Trial

BACKGROUNDThe optimal intensity of myeloablation delivered as part of a reduced-intensity/toxicity conditioning (RIC/RTC) regimen to decrease the recurrence rate, without increasing nonrecurrence mortality (NRM), remains to be established. METHODSThe current phase 2, prospective, multicenter trial aimed to assess the efficacy and safety of an RIC/RTC regimen based on busulfan at a dose of 130 mg/m(2)/day intravenously for 3 days, fludarabine at a dose of 30 mg/m(2)/day for 5 days, and antithymocyte globulins at a dose of 2.5 mg/kg/day for 2 days. A total of 80 patients (median age, 53 years; range, 25-64 years) with hematological malignancies were included. RESULTSWith a median follow-up of 21 months (range, 12-36.5 months), the Kaplan-Meier estimates of overall and disease-free survival at 2 years were 62% (95% confidence interval [95% CI], 51%-73%) and 50% (95% CI, 33%-57%), respectively. The cumulative incidences of grade 2 to 4 acute graft-versus-host disease (GVHD) and chronic GVHD (all grades) were 29% (95% CI, 19%-39%) and 35% (95% CI, 24%-46%), respectively. At 2 years, the cumulative incidence of recurrence/disease progression and NRM were 44% (95% CI, 31%-56%) and 11% (95% CI, 6%-19%), respectively. Patient age, diagnosis, donor type, sex, presence of comorbidities, and the Hematopoietic cell transplantation-specific comorbidities index did not appear to have any statistically significant impact on NRM, recurrence/disease progression, disease-free survival, or overall survival. CONCLUSIONSThe RIC/RTC regimen used in the current study appeared to be safe, with a low NRM rate at 2 years noted among high-risk patients, and efficient disease control, warranting prospective phase 3 trials. Cancer 2015;121:562-569. (c) 2014 American Cancer Society. The reduced toxicity regimen based on a busulfan dose of 130 mg/m(2)/day intravenously for 3 days, fludarabine at a dose of 30 mg/m(2)/day for 5 days, and antithymocyte globulins at a dose of 2.5 mg/kg/day for 2 days was evaluated in a prospective phase 2 trial. This regimen appeared to be safe, with a low nonrecurrence mortality rate at 2 years in high-risk patients, and efficient disease control, thereby warranting prospective phase 3 trials.