High-Risk Acute Promyelocytic Leukemia with Unusual T/Myeloid Immunophenotype Successfully Treated with ATRA and Arsenic Trioxide-Based Regimen.

We describe two patients with acute promyelocytic leukemia (APL) with an unusual immunophenotype with co-expression of myeloperoxidase (MPO) with cytoplasmic CD3 (cCD3) representing myeloid and T-lineage differentiation. Both harbored FLT3-ITD mutations. One additionally had a deletion in the PML gene affecting the primer binding site, thus limiting measurable residual disease (MRD) analysis during follow-up. Both patients achieved durable remission with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapy, thus mitigating the need for repetitive conventional chemotherapy cycles and allogeneic stem cell transplantation. Our report highlights the complexity and challenge of diagnosis and management of APL due to the variant immunophenotype and genetics, and underscores the importance of synthesizing information from all testing modalities. The association of the unusual immunophenotype and FLT3-ITD mutation illustrates the plasticity of the hematopoietic stem cell and the pathobiology of leukemia with mixed lineage or lineage infidelity.