Blood Count Recovery Following Induction Therapy for Acute Myeloid Leukemia in Children Does Not Predict Survival

SIMPLE SUMMARY: International Working Group (IWG) and European LeukemiaNet (ELN) adult response definitions are currently used to evaluate the efficacy of new agents for childhood acute myeloid leukemia (AML); however, the criteria are not consistent with consensus definitions used in pediatric trials or the common practice of intensifying treatment prior to full hematopoietic recovery of ANC ≥ 1000 cells/μL and platelets ≥ 100 cells/μL. This retrospective analysis of the two most recent Phase 3 AML trials in the Children’s Oncology Group assesses the incidence, timing, and prognostic significance of count recovery following induction chemotherapy in children with AML. These data confirm that awaiting count recovery to meet adult criteria does not reflect standard practice in pediatric AML and IWG/ELN-defined CR does not have a significant impact on survival in children. Continuing to use adult IWG/ELN count recovery definitions limits childhood AML drug development by underestimating response, and therefore, updated response criteria are needed for pediatric AML patients. ABSTRACT: International Working Group (IWG) and European LeukemiaNet (ELN) response definitions are utilized to evaluate the efficacy of new agents for childhood acute myeloid leukemia (AML) for regulatory purposes. However, these criteria are not consistent with definitions used in pediatric AML trials or with standard pediatric practice to proceed with subsequent therapy cycles prior to IWG/ELN-defined count recovery. We retrospectively analyzed data from the two most recent Phase 3 pediatric AML clinical trials conducted by the Children’s Oncology Group (COG) to assess the incidence, timing, and prognostic significance of count recovery following induction chemotherapy. Of the patients with fewer than 5% bone marrow blasts at the end of first induction, 21.5% of patients proceeded to a second induction cycle prior to achieving ANC ≥ 500 cells/μL and platelets ≥ 50,000 cells/μL, both well below the IWG/ELN thresholds of ANC > 1000 cells/μL and platelets > 100,000 cells/μL. In these two sequential childhood AML Phase 3 trials, neither ANC nor platelet recovery predicted survival. Intensification of treatment through the initiation of subsequent therapy cycles prior to attainment of IWG/ELN-defined CR is common practice in clinical trials for children with AML, suggesting that updated response definitions are needed for pediatric AML.