Abstract
6561 Background: We could recently show that stimulation of CLL cells with CD40 ligand (CD40L) increased the frequency of metaphases of CLL cells which are then suitable for chromosome banding. We compared this new technique, CEC, with clinical data from CLL patients (pts) and data obtained by fluorescence in situ hybridization (FISH). Methods: Blood samples from 95 CLL pts (Binet A: 31.1%, B: 30.0%, C: 38.9%; 57% untreated, 43% previously treated) were subjected to simultaneous analysis by CEC and FISH. Results: Chromosomal aberrations were detected in 89.5% of pts by CEC with a range of 0 to 14 chromosomal aberrations per sample (2.28±2.6; mean±SD). All chromosomes except the X chromosome showed abnormalities. All major genetic abnormalities detected were also observed by FISH (11q-: 13.8%, +12: 12.2%, 13q-: 63.4%, 17p-: 6.1%, no abnormalities: 20.7% of pts). In addition, using CEC, translocations were detected in 34.7% of the CLL pts (balanced: 23.2%, unbalanced: 16.8% of the pts). The majority of these translocations (balanced: 87%, unbalanced: 96%) were so far not described for B-CLL cases. Regarding treatment free survival (TFS) we were able to confirm the prognostic significance of 17p- (p=0.0271) and CD38 (log rank test: 19.37, p<0.0001) in our patient cohort, while the incidence of translocations proved to be an even stronger prognosticator for TFS (log rank test: 24.95, p<0.0001, median TFS 24 vs. 105 months). In a multivariate analysis, translocations were the most adverse prognostic factor on TFS (p<0.001). The frequent aberrations detected by FISH (11q-, +12, 13q-) were not associated with translocations but pts with CD38 (p= 0.018) or 17p- (p= 0.044) represent subgroups of pts with translocations. Conclusions: A new technique, CD40L-enhanced conventional chromosome banding, is able to detect more and new chromosomal aberrations in CLL compared to FISH analysis. In about one third of pts unbalanced or balanced translocations were identified. Translocations had the strongest negative impact on TFS in our cohort and should be considered as a new prognostic factor in CLL. No significant financial relationships to disclose.
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