Altres ajuts: The authors want to thank Marta Salido, Carme Melero, Ana Batlle, Mª Ángeles Piñán, Alicia Rodríguez and George Papaioannou for their contribution to the study providing clinical or laboratory data, Sergi Mojal for statistical review, and Grupo Cooperativo Español de Citogenética Hematológica (GCECGH) and Grupo Español de Leucemia Linfática Crónica (GELLC). This work has been supported by "Xarxa de Bancs de tumors" sponsored by Pla Director d'Oncologia de Catalunya (XBTC) and Fundació La Caixa; the Swedish Cancer Society, the Swedish Research Council, the Lion's Cancer Research Foundation, and Selander's Foundation, Uppsala; H2020 "AEGLE, An analytics framework for integrated and personalized healthcare services in Europe" by the EU.

Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53 abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p−) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53 abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p− and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, ≥3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10-year overall survival (OS), 8p− (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53 abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.