PersonALL: a genetic scoring guide for personalized risk assessment in pediatric B-cell precursor acute lymphoblastic leukemia

Bedics, Gábor and Egyed, Bálint and Kotmayer, Lili and Benard-Slagter, Anne and de Groot, Karel and Bekő, Anna and Hegyi, Lajos and Bátai, Bence and Krizsán, Szilvia and Kriván, Gergely and Erdélyi, Dániel and Müller, Judit and Haltrich, Irén and Kajtár, Béla and Pajor, László and Vojcek, Ágnes and Ottóffy, Gábor and Ujfalusi, Anikó and Szegedi, István and Tiszlavicz, Lilla and Bartyik, Katalin and Csanádi, Krisztina and Péter, György and Simon, Réka and Hauser, Péter and Kelemen, Ágnes and Sebestyén, Endre and Jakab, Zsuzsanna and Matolcsy, András and Kiss, Csongor and Kovács, Gábor and Savola, Suvi and Bödör, Csaba and Alpár, Donát (2023) PersonALL: a genetic scoring guide for personalized risk assessment in pediatric B-cell precursor acute lymphoblastic leukemia. BRITISH JOURNAL OF CANCER, 129. pp. 455-465. ISSN 0007-0920

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Abstract

BACKGROUND: Recurrent genetic lesions provide basis for risk assessment in pediatric acute lymphoblastic leukemia (ALL). However, current prognostic classifiers rely on a limited number of predefined sets of alterations. METHODS: Disease-relevant copy number aberrations (CNAs) were screened genome-wide in 260 children with B-cell precursor ALL. Results were integrated with cytogenetic data to improve risk assessment. RESULTS: CNAs were detected in 93.8% (n = 244) of the patients. First, cytogenetic profiles were combined with IKZF1 status (IKZF1normal, IKZF1del and IKZF1plus) and three prognostic subgroups were distinguished with significantly different 5-year event-free survival (EFS) rates, IKAROS-low (n = 215): 86.3%, IKAROS-medium (n = 27): 57.4% and IKAROS-high (n = 18): 37.5%. Second, contribution of genetic aberrations to the clinical outcome was assessed and an aberration-specific score was assigned to each prognostically relevant alteration. By aggregating the scores of aberrations emerging in individual patients, personalized cumulative values were calculated and used for defining four prognostic subgroups with distinct clinical outcomes. Two favorable subgroups included 60% of patients (n = 157) with a 5-year EFS of 96.3% (excellent risk, n = 105) and 87.2% (good risk, n = 52), respectively; while 40% of patients (n = 103) showed high (n = 74) or ultra-poor (n = 29) risk profile (5-year EFS: 67.4% and 39.0%, respectively). CONCLUSIONS: PersonALL, our conceptually novel prognostic classifier considers all combinations of co-segregating genetic alterations, providing a highly personalized patient stratification.

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