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

• Published in: Modern pathology Vol. 31; no. 8; pp. 1318 - 1331
• Main Authors: Matarraz, Sergio, Leoz, Pilar, Fernández, Carlos, Colado, Enrique, Chillón, María Carmen, Vidriales, María Belén, González, Marcos, Rivera, Daniel, Osuna, Carlos Salvador, Caballero-Velázquez, Teresa, Van Der Velden, Vincent, Jongen-Lavrencic, Mojca, Gutiérrez, Oliver, Bermejo, Ana Yeguas, Alonso, Luis García, García, Monique Bourgeois, De Ramón Sánchez, Cristina, García-Donas, Gloria, Mateo, Aránzazu García, Recio, Isabel, Sánchez-Real, Javier, Mayado, Andrea, Gutiérrez, María Laura, Bárcena, Paloma, Barrena, Susana, López, Antonio, Van Dongen, Jacques, Orfao, Alberto
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2018; Elsevier Limited
• Subjects: 13/31; 14/63; 38/32; 38/77; 692/53/2423; 692/699/67/1990/283/1897; Acute promyeloid leukemia; Adolescent; Adult; Aged; Aged, 80 and over; Basophils - pathology; Bleeding; Bone marrow; CD22 antigen; CD34 antigen; CD7 antigen; Cell Lineage; Child; Child, Preschool; Diagnosis; Female; Fibrinogen; Hemorrhage; Hemorrhage - etiology; Humans; Laboratory Medicine; Leukemia; Leukemia, Promyelocytic, Acute - complications; Leukemia, Promyelocytic, Acute - pathology; Lymphocyte receptors; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Pathology; Patients; Phenotype; Phenotypes; Promyeloid leukemia; Young Adult
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-018-0038-2

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.