Mixed phenotype acute leukemia: 13 patients and a proposed management algorithm

Mixed phenotype acute leukemia (MPAL) is a rare, heterogeneous group of acute leukemias of ambiguous lineage (2-5% of cases) with no consensus treatment. We retrospectively reviewed all patients with MPAL managed in a single Tunisian hematology department between January 2014 and December 2023. Diagnosis relied on multiparameter flow-cytometric immunophenotyping using the EGIL score and the WHO classifications; survival was estimated by the Kaplan-Meier method. Thirteen patients were included (median age 23 years, range 2-46; sex ratio ≈ 1.1). Twelve had a B/myeloid and one a T/myeloid phenotype; on cross-classification, 11 of the 13 EGIL-defined cases also fulfilled the stricter WHO criteria. Cytogenetic abnormalities were found in 10 patients, including t(9;22) in two and a complex karyotype in three. Eleven patients received an ALL-type induction, with a tyrosine kinase inhibitor in BCR-ABL1-positive disease; complete remission was obtained in 9 of 11 evaluable patients, and two underwent allogeneic stem-cell transplantation. Treatment-related mortality was high (53.8%), mainly infectious, and median overall survival was 19.2 months (1- and 5-year overall survival 54% and 30.8%). This series, one of the first dedicated cohorts from Tunisia, confirms the rarity and severity of MPAL and supports precise diagnosis, individualized multidisciplinary management, and multicenter collaboration.