Background: Chronic lymphocytic leukemia (CLL) stratification mainly relies on FISH markers according to Döhner's hierarchical model which includes high-risk FISH markers, intermediate FISH, or low-risk FISH. Recently, complex karyotype (CK) has been demonstrated as an independent negative prognostic factor in CLL.

Methods: A series of 1012 untreated CLL patients have been investigated with both FISH and chromosome banding analysis (CBA) on the same pellet obtained from interleukin IL-2-CPG DSP30 oligonucleotide-stimulated cultured cells.

Results: Combining both FISH and CBA has led to refine prognostic categories with identification of 30% of CK in low-risk and intermediate FISH group. This raises the issue of switching them to a high-risk group. While this series confirmed the significant association between CK and high-risk FISH (P = .003), 33% of CK present no ATM or TP53 deletion. Three groups characterized by significant association between FISH markers and CBA have emerged: CK with TP53 loss and monosomy 15; CK with ATM loss and 14q32 translocation; and CK without ATM or TP53 losses but trisomies 12, 18, and 19 or t(14;18)(q32;q21).

Conclusion: We have observed that in addition to FISH analysis, the CBA allows detection of many abnormalities with potential impact on patient follow-up and treatment, mainly CK.

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