Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

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.

A novel flow cytometric method for enhancing acute promyelocytic leukemia screening by multidimensional dot-plots

“…To the best of our knowledge, we were the first to examine APL with multidimensional dot-plots based on a wide range of markers. We used not only the markers the expression of which was frequently altered in APL (CD34, CD117, HLA-DR, CD15, cyMPO, CD13, CD33, CD64) but also the prognostic markers, such as CD56, CD7, CD2, and cyFXIII-A [22, 29–32]. The expression of CD56 or CD7 marker is associated with poor prognosis [29], while the presence of cyFXIII-A or CD2 with good prognosis [22, 31].…”

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

“…28 Recently, it was found that a high expression of the basophil marker, CD203c, in the leukemic cells after starting therapy is also correlated with bleeding. 29 The reason for this is unknown.…”

Promielocitos leucémicos con características asociadas con la maduración de basófilos: ¿un nuevo predictor de hemorragia severa?

“…Matarraz et al hallaron que la expresión de marcadores asociados a basófilos, como CD203c y CD22, en promielocitos leucémicos, se asocia a un mayor riesgo de sangrado severo y a una menor sobrevida global. Estos casos también mostraron características citomorfológicas asociadas con la maduración de los basófilos (2) . En este reporte mostramos el extendido de médula ósea (Figura 1) y el inmunofenotipo por citometría de flujo multiparamétrica (Figura 2) de promielocitos leucémicos con características asociadas a diferenciación de basófilos, correspondientes a un paciente con diagnóstico de LPA con sangrado importante en sistema nervioso central al momento del diagnóstico.…”