%0 Journal Article
%A Matarraz, Sergio
%A Leoz, Pilar
%A Fernández, Carlos
%A Colado, Enrique
%A Chillón, María Carmen
%A Vidriales, María Belén
%A González, Marcos
%A Rivera, Daniel
%A Osuna, Carlos Salvador
%A Caballero-Velázquez, Teresa
%A Van Der Velden, Vincent
%A Jongen-Lavrencic, Mojca
%A Gutiérrez, Oliver
%A Bermejo, Ana Yeguas
%A Alonso, Luis García
%A García, Monique Bourgeois
%A De Ramón Sánchez, Cristina
%A García-Donas, Gloria
%A Mateo, Aránzazu García
%A Recio, Isabel
%A Sánchez-Real, Javier
%A Mayado, Andrea
%A Gutiérrez, María Laura
%A Bárcena, Paloma
%A Barrena, Susana
%A López, Antonio
%A Van Dongen, Jacques
%A Orfao, Alberto
%T Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.
%D 2018
%U http://hdl.handle.net/10668/12271
%X 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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