Mixed Phenotype Acute Leukemia: Current Approaches to Diagnosis and Treatment

Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia with features of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The review examines current definitions and controversies in classification of MPAL, new insights into genomic drivers and pathogenesis, recent evidence to support treatment recommendations, and opportunities for future research. Recent collaborative efforts have made progress in understanding the genomic landscape and optimal therapy for MPAL. The preponderance of retrospective data supports beginning therapy with ALL directed regimens. Differences in prognosis for adult and children with MPAL have led to divergent approaches for therapy intensity, including use of stem cell transplantation consolidation. MPAL remains a challenging leukemia to understand, research, and treat due to low incidence, shifting and subjective approaches to classification, and innate biological heterogeneity. Ongoing research hopes to surmount these obstacles through prospective studies within large cooperative groups to provide new insight into targetable biology and further refine optimal therapy.