Immunophenotypic Characterisation of Mixed Phenotype Acute Leukemia: A Review of Published Series

Abstract

Mixed phenotype acute leukaemia is defined by antigen expression thresholds expressed relative to normal cells, and the resulting label determines whether a patient receives lymphoblastic-directed or myeloid-directed therapy. Since lymphoblastic-directed treatment produces better outcomes, a relative flow cytometric measurement is doing more clinical work than its reproducibility comfortably supports. Objectives: To review the published evidence on immunophenotypic characterisation of mixed phenotype acute leukaemia: which markers define each lineage and at what thresholds, how the lineage combinations distribute, how immunophenotype relates to morphology and cytogenetics, and how the assignment influences treatment and outcome.
Material and Methods: Narrative review of clinicopathological series, classification documents, diagnostic reviews and case reports indexed in PubMed and the major haematology and pathology journals. Studies were eligible if they reported immunophenotypic features, diagnostic criteria or outcomes in a defined mixed phenotype acute leukaemia population. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: Across 100 cases meeting consensus criteria, immunophenotyping showed B and myeloid combinations in 59 per cent, T and myeloid in 35, B and T in 4 and trilineage in 2 per cent. Morphology was consistent with lymphoblastic leukaemia in 43 per cent, myeloid in 42 and inconclusive in 15, and there was no correlation between age, morphology, immunophenotype or cytogenetics. Cytogenetic findings were complex in 32 per cent, otherwise aberrant in 27, t(9;22) in 20, normal in 13 and 11q23 rearranged in 8 per cent. In a separate series of 52 patients, 69.2 per cent received lymphoblastic-directed and 30.8 per cent myeloid-directed regimens, complete remission was achieved in 76.9 per cent, and lymphoblastic-directed treatment, paediatric age and biphenotypic blast type were each associated with higher remission rates and better overall survival.Conclusion: Morphology contributes almost nothing to the diagnosis and the  immunophenotype carries it entirely. Because the thresholds are relative rather than absolute and because lineage can switch under treatment pressure, the assignment is less stable than the treatment decision resting on it. Abbreviations: MPAL – Mixed Phenotype Acute Leukaemia, ALAL – Acute Leukaemia of Ambiguous Lineage, BAL – Biphenotypic Acute Leukaemia, ALL – Acute Lymphoblastic Leukaemia, AML – Acute Myeloid Leukaemia, MPO – Myeloperoxidase, cCD3 – Cytoplasmic CD3, sCD3 – Surface CD3, EGIL –
European Group for the Immunological Characterization of Leukemias, WHO – World Health Organization, ICC – International Consensus Classification, NSE – Nonspecific Esterase, My+ ALL – Myeloid Antigen-Positive ALL, CR – Complete Remission.