Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study

To assess the value of administering timed-sequential chemotherapy (TSC) (two therapeutic sequences separated by a four-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients aged 15 to 50 years were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. Two hundred and thirty seven patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the two consolidation arms (5-year event-free survival (EFS): 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML (CN-AML) NPM1 + or CEBPA + and FLT3-ITD - had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; p = 0.02), especially CN-AML (5-year EFS: 48% vs 31%; p = 0.04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adult as compared to HDAraC. This trial is registered at www.clinicaltrials.gov as no. [NCT00880243][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00880243&atom=%2Fbloodjournal%2Fearly%2F2011%2F06%2F20%2Fblood-2011-04-349258.atom