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Baliakas, Panagiotis; Jeromin, Sabine; Iskas, Michalis; Puiggros, Anna; Plevova, Karla; Nguyen-Khac, Florence; Davis, Zadie; Rigolin, Gian Matteo; Visentin, Andrea; Xochelli, Aliki; Delgado, Julio; Baran-Marszak, Fanny; Stalika, Evangelia; Abrisqueta, Pau; Durechova, Kristina; Papaioannou, George; Eclache, Virginie; Dimou, Maria; Iliakis, Theodoros; Collado, Rosa; Doubek, Michael; Calasanz, M. Jose; Ruiz-Xiville, Neus; Moreno, Carolina; Jarosova, Marie; Leeksma, Alexander C.; Panayiotidis, Panayiotis; Podgornik, Helena; Cymbalista, Florence; Anagnostopoulos, Achilles; Trentin, Livio; Stavroyianni, Niki; Davi, Fred; Ghia, Paolo; Kater, Arnon P.; Cuneo, Antonio; Pospisilova, Sarka; Espinet, Blanca; Athanasiadou, Anastasia; Oscier, David; Haferlach, Claudia; Stamatopoulos, Kostas
Blood, 03/2019, Letnik: 133, Številka: 11Journal Article
Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations TP53abs), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with +12,+19, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with ≥5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL. •Complex karyotype defined by the presence of ≥3 chromosomal abnormalities should not be axiomatically considered unfavorable in CLL.•High cytogenetic complexity with ≥5 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Display omitted
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