Clinical Outcomes in Pediatric Mixed Phenotype Acute Leukemia (MPAL) Differ Depending on Disease Classification Criteria; A Multi-Center Cohort Study

▪ Mixed phenotype acute leukemia (MPAL) is a category of acute leukemia established in the World Health Organization (WHO) 2001 classification, significantly modified in WHO2008, and again refined in the most recent WHO2016 update. The current WHO2016 iteration conceptualizes MPAL as a stem cell disorder whereby most cases will manifest heterogeneity of lineage-specific antigen expression by multi-parameter flow cytometry. The WHO2016 definition also urges caution for cases otherwise consistent with B-cell acute lymphoblastic leukemia (B-ALL) that express myeloperoxidase (MPO) as the sole representation of myeloid lineage. These cases met the WHO2008 definition but may not meet the newer WHO2016 criteria. There is limited data on the clinical impact of these recent changes in the WHO classification for MPAL. Six institutions identified cases diagnosed as MPAL between 2008 and 2016 according to WHO criteria. The diagnostic flow cytometry was then reanalyzed by two independent hematopathologists blinded to clinical outcomes. The cases were evaluated as to whether they met criteria for WHO2008 MPAL and/or WHO2016 MPAL. Cases of WHO2008 MPAL were further subdivided into those that otherwise met criteria for B-ALL (including non-lineage specific expression of ±CD13, ±CD15, ±CD33) but qualified as MPAL due to MPO expression (MPO+MPAL) and all remaining cases of MPAL that demonstrated additional myeloid lineage specificity as described by the WHO criteria (MLS+MPAL). Data for a distinct cohort of pediatric B-ALL without significant MPO expression diagnosed during the same study period was submitted from one participating site to serve as a reference cohort (n=258). Endpoints of interest to evaluate clinical outcomes according to the WHO classification were event-free and overall survival (EFS, OS). All statistical tests were two-sided with significance set at p