Risk-Stratified Therapy for Pediatric Acute Myeloid Leukemia

Abstract

Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically improved in the past 40 years, currently reaching 70% to 80% in developed countries. This was accomplished by the intensification of conventional chemotherapy, improvement in risk stratification using leukemia-specific cytogenetics/molecular genetics and measurable residual disease, appropriate use of allogeneic hematopoietic stem cell transplantation, and improvement in supportive care. However, the principle therapeutic approach for pediatric AML has not changed substantially for decades and improvement in event-free survival is rather modest. Further refinements in risk stratification and the introduction of emerging novel therapies to contemporary therapy, through international collaboration, would be key solutions for further improvements in outcomes.

Keywords: acute myeloid leukemia; chemotherapy; children; cytogenetics; hematopoietic stem cell transplantation; measurable residual disease; molecular genetics; novel therapy.

Figure 1

Genetic profiles of pediatric AML. Data is from the JPLSG AML-05 study. * Percentage of the patients with FLT3-ITD per total patients (e.g., patients with RUNX1::RUNX1T1 and FLT3-ITD accounts for 0.8% of all 369 cases).

Figure 2

Induction therapy used in pediatric AML.