Impact of Molecular Risk on Efficacy of Blood and Marrow Transplantation for Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Outcomes for children and adolescents with newly diagnosed acute myeloid leukemia (AML) have only shown modest improvement over the past three decades. Additionally, outcomes for relapsed disease continue to be poor. As a result, there is a pressing need to optimize consolidation therapy to ensure deep and persistent remissions and prevent future relapse. In particular, the utility of bone and marrow transplant (BMT) for consolidation in pediatric AML has been debated for decades. A prior Children's Oncology Group (COG) study risk-stratified patients on the basis of cytogenetic alterations and demonstrated that consolidative BMT performed in first complete remission (CR1) improved long-term outcomes specifically in patients diagnosed with intermediate-risk disease, but found no survival benefit in patients with either low- or high-risk disease. Since then, whole genome and transcriptome sequencing have uncovered a large number of somatic mutations and cryptic fusions that carry prognostic significance in pediatric AML. Combining these molecular features with traditional cytogenetic risk stratification results in the re-classification of a significant number of patients. While this cytomolecular risk stratification is now being used in contemporary clinical trials (e.g., AAML1831/NCT04293562), the merits of consolidative BMT have not been rigorously re-assessed using these newly defined risk strata.