High-dose cytarabine induction therapy and flow cytometric measurable residual disease monitoring for children with acute myeloid leukemia.

Abstract Japanese Pediatric Leukemia/Lymphoma Study Group AML-12 is a seamless phase II/III cooperative study to evaluate a role of high-dose cytarabine (HDAC) in initial induction therapy and significance of measurable residual disease (MRD) at end of induction therapies for children with acute myeloid leukemia (AML). From 2014 to 2018, a total of 359 patients were enrolled; 324 patients were randomly assigned to receive standard-dose cytarabine induction or HDAC induction. Following the common second induction, patients achieving remission were stratified into either of the three risk groups and received consolidation chemotherapy with or without allogeneic hematopoietic stem cell transplantation. MRD was centrally monitored at end of Induction-1 (TP-1) and end of Induction-2. There were no significant statistical differences in the primary endpoints between the two arms; MRD-positive (≥ 0.1%) rate at TP-1 (21.5% vs. 25.2%, P = 0.517) and 3-year event-free survival rate (64.3% [95%CI, 56.5% – 71.0%] vs. 61.2% [53.1% – 68.4%], P = 0.589). MRD could be measured for 262 (94.9%) of the 276 patients for whom MRD monitoring was attempted and was demonstrated to be the strongest factor to predict the outcomes. Although, HDAC in initial induction did not improve the outcomes of children with AML, flow cytometric MRD monitoring was feasible and highly prognostic.