Pediatric therapy-related hematologic neoplasms show enrichment for <italic>KMT2A</italic> rearrangement and lymphoblastic phenotype.

AbstractIn children, therapy-related hematologic neoplasms (t-HN) are uncommon. Many are driven by genetic events independent of clonal hematopoiesis. We sought to understand the clinical and genetic factors of pediatric t-HN in a large independent cohort. Fifty-six t-HN were retrospectively identified. Chromosome microarray, next-generation and/or RNA sequencing were performed. Patients had primary hematologic, solid, or central nervous system tumors. t-HN included myeloid (t-MN) and lymphoblastic (t-ALL) phenotypes. Approximately half of the cases harbored <italic>KMTA2A</italic> rearrangement (<italic>KMT2A</italic>r). Among t-HN without <italic>KMT2A</italic>r, genetic drivers were heterogeneous, including diverse fusions or aneuploidy. Approximately 18% harbored 17p deletions and/or <italic>TP53</italic> mutations. EFS/OS was not associated with t-HN lineage or <italic>KMT2A</italic>r, but HSCT was associated with improved EFS and OS. We detail one of the largest cohorts to date of pediatric t-HN, confirming frequent <italic>KMT2A</italic>r and t-ALL. [ABSTRACT FROM AUTHOR]