TY - JOUR AU - Mohamad Mohty, AU - Florent Malard, AU - Didier Blaise, AU - Noel Milpied, AU - Gérard Socié, AU - Anne Huynh, AU - Oumédaly Reman, AU - Ibrahim Yakoub-Agha, AU - Sabine Furst, AU - Thierry Guillaume, AU - Resa Tabrizi, AU - Stéphane Vigouroux, AU - Pierre Peterlin, AU - Jean El-Cheikh, AU - Philippe Moreau, AU - Myriam Labopin, AU - Patrice Chevallier, PY - 2016/12/31 Y2 - 2024/03/28 TI - Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia JF - Haematologica JA - haematol VL - 102 IS - 1 SE - Articles DO - 10.3324/haematol.2016.150326 UR - https://haematologica.org/article/view/7938 SP - 184-191 AB - The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. ER -