Abstract
B-lymphoid/myeloid mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia that most likely originates from hematopoietic pluripotent stem cells. It is a heterogeneous group of leukemia characterized by the expression of more than 1 specific marker from each hematopoietic lineage (lymphoid and myeloid-specific antigens). The MLL-AF4 fusion gene is a common genetic abnormality in MPAL. Due to the lack of thorough understanding and the rare occurrence of B-lymphoid/myeloid MPAL, it presents substantial challenges in determining the standard treatment protocol. The absence of a widely accepted optimal treatment for MPAL has indicated the need for a more effective and less toxic approach. This case report presents two cases of B-lymphoid/myeloid MPAL with MLL-AF4 genetic abnormality successfully treated with a chemo-free regimen composed of venetoclax, hypomethylating agents, and blinatumomab and achieved complete remission (CR). Considering the results of this case report, the combination of a chemotherapy-free regimen could be considered a safe and effective treatment approach for patients with B-lymphoid/myeloid MPAL.