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  • Title: Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.
    Author: Matarraz S, Leoz P, Fernández C, Colado E, Chillón MC, Vidriales MB, González M, Rivera D, Osuna CS, Caballero-Velázquez T, Van Der Velden V, Jongen-Lavrencic M, Gutiérrez O, Bermejo AY, Alonso LG, García MB, De Ramón Sánchez C, García-Donas G, Mateo AG, Recio I, Sánchez-Real J, Mayado A, Gutiérrez ML, Bárcena P, Barrena S, López A, Van Dongen J, Orfao A.
    Journal: Mod Pathol; 2018 Aug; 31(8):1318-1331. PubMed ID: 29572500.
    Abstract:
    Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.
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