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

Abstract

BACKGROUND: The 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. METHODS: The 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/m2/day intravenously for 3 days, fludarabine at a dose of 30 mg/m2/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. RESULTS: With 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. CONCLUSIONS: The 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.