It is unclear whether karyotype aberrations occurring in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel, have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC, n=64) and in a validation cohort (VC, n=84) of CLL with "normal" FISH. An abnormal karyotype was found in 21.5% and 35,7% of cases in the LC and VC, respectively, and was associated with lower immunophenotypic score (p=0.030 in the LC, 0.035 in the VC), advanced stage (p=0.040 in the VC) and need of treatment (p=0.002 in the LC, <0.0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In CLL patients with "normal" FISH, karyotypic aberrations by conventional cytogenetics using novel mitogens identify a subset of cases with adverse prognostic features
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