Optimal therapeutic strategies for mixed phenotype acute leukemia

Mixed phenotype acute leukemia (MPAL) encompasses a rare group of clinically, immunophenotypically, and genetically diverse leukemias. Diagnosing and treating these patients remains challenging. In recent years, systematic efforts have been made to better define the genetic landscape of MPAL. These insights allow better understanding of the pathophysiology of MPAL, have the potential for a more biologically meaningful classification and may promote targeted, novel approaches to treat these leukemias.

Recent studies suggest that MPALs originate in a multipotent primitive cell, demonstrate large genetic diversity and include subgroups that may benefit from targeted therapy. Recent data support the use of ALL-type induction followed by allogeneic stem cell transplantation in first remission for most adults. Novel targeted approaches hold promise for treatment of MPAL; however, some may unpredictably select for clonal expansion of cells from a different lineage than observed at presentation.

A biologically and genetically driven classification of MPAL may yield more accurate prognosis and potentially direct therapy in patients with MPAL. Prospective efforts that incorporate targeted approaches based on genetics and immunophenotype are warranted.