Leveraging genomic diagnostics for prognostics and therapeutics in pediatric acute leukemia.

Advancements in the rapidity, cost efficacy, and sensitivity of next-generation sequencing (NGS) have facilitated molecular risk stratification and precision medicine-based treatment for pediatric leukemia. The benefit of uniform cytomolecular analyses for clinical trial risk assignment is clear. However, the clinical impact of comprehensive NGS for pediatric leukemias at an institutional level is not well described. We report the genomic spectrum of one of the largest cohorts of pediatric and adolescent/young adult (AYA) acute leukemias examined to date ( = 1442) via institutional NGS testing from our large tertiary care center. We evaluated the clinical utility of genomic results for informing prognosis and treatment. We identified high utility of the comprehensive DNA-based mutational panel and RNA-fusion panel, which detected leukemia-associated variants in 99% of specimens. We observed 65% of B-cell acute lymphoblastic leukemia cases and 69% of patients with acute myeloid leukemia harbored a prognostic molecular alteration. In total, 325 of 1134 patients (29%) harbored potentially targetable molecular biomarkers, and 23% of cases with follow-up data received precision medicine-based therapy. Paired diagnostic and relapsed leukemia samples aided in differentiation between treatment-related leukemia versus lineage drift/switch. These findings demonstrate the broad utility of comprehensive molecular sequencing for pediatric/AYA leukemia at an institutional level to improve outcomes.