Mixed-phenotype acute leukemia: Current challenges in diagnosis and therapy

Purpose of review Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. Recent findings Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors. The limited available data suggest that higher remission rates are achieved with acute lymphoblastic leukemia-like induction regimens compared with acute myeloid leukemia-type approaches. Allogeneic transplantation in first remission may be associated with improved survival compared with consolidation chemotherapy. Summary Advances in understanding the genetic landscape of MPAL may allow a more biologically driven classification of this heterogeneous group of leukemias in the future that will lead to optimized therapies for individual patients. Most data that inform therapy are based on retrospective, uncontrolled studies; prospective trials that incorporate targeted approaches based on genetics and immunophenotype are needed.