Immunophenotypically Defined Mixed‐Phenotype Acute Leukemias: A Clinicopathologic Analysis of 52 Cases

Abstract Background Immunophenotypically defined mixed‐phenotype acute leukemias (MPAL) are rare and remain a diagnostic and therapeutic dilemma. We aim to explore the clinicopathologic characteristics and oncological outcomes of these entities. Methods A total of 52 patients with immunophenotypically defined MPAL were identified from our pathology database. Medical records and archived diagnostic pathology data were retrospectively reviewed and analyzed. Results This cohort consisted primarily of B/myeloid (80.8%), followed by T/myeloid (11.5%), B/T (5.8%), and B/T/myeloid (1.9%) immunophenotypes. There were 19 adults and 33 pediatric patients, with a male‐to‐female ratio of 2.1:1. A total of 34 biphenotypic and 18 bilineal MPAL patients were observed. Comparative analyses suggested that acute lymphoblastic leukemia (ALL)‐directed chemotherapy, pediatric population, and biphenotypic type significantly correlated with higher complete remission rates ( p = 0.007, p < 0.001, and p = 0.021, respectively); however, statistically significant differences were not observed in relapse rates ( p = 0.343, p = 0.232, and p = 0.690, respectively). Survival analyses revealed that ALL‐directed chemotherapy, pediatric population, and B‐MPAL subtype (i.e., B/myeloid, B/T, and B/T/myeloid) correlated with significantly better overall survival ( p < 0.001, p < 0.001, and p = 0.006, respectively). Conclusion Our findings support that immunophenotypically defined MPALs are distinctive entities with immunophenotypic diversity. Multiple factors, including treatment type, lineage component, and age group, represent strong predictors of clinical outcomes. Future studies focusing on incorporating immunophenotype and molecular profiles may contribute to better classification, prognostication, and treatment establishment. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission