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Reply to the prognostic difference of monoallelic versus biallelic deletion of 13q in chronic lymphocytic leukemia

In a recent online paper on del13q14 chronic lymphocytic leukemia (CLL), Garg at al state that neither pattern of deletion (monoversus biallelic) nor the percentage of deleted cells influences risk of progression. Interestingly, in 12 patients who had a repeat fluorescent in situ hybridization (FISH) analysis, an increase in the number of deleted cells was detected. In light of these data, we reviewed our del13q14-CLL patients who were monitored by FISH during their clinical course. Between 2001 and 2009, del13q14 was identified as the sole abnormality in 137 of 352 CLL patients (39%). Baseline FISH analysis was performed at diagnosis or within 12 months (probes: LSID13S319 and LSI-Rb1, LSI-ATM, LSI-p53, CEP12; Vysis, Downers Grove, Ill). D13S319 deletion was monoallelic in 121 cases (88%) and biallelic in 16. The median percentage of abnormal nuclei was 50% (range, 15%-96%) and was higher in patients with a biallelic pattern (73% vs 49%; P < .0001, MannWhitney test). With a median follow-up of 59 months (range, 12-124 months), the 5-year treatment-free survival rate was 54% (Kaplan-Meier). As a continuous variable, the baseline percentage of abnormal nuclei was related to progression (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.04; P 1⁄4 .0002; Cox regression), whereas the pattern of deletion was not significant. Repeat FISH analyses were performed on 100 patients (median interval from baseline to repeat FISH analysis, 36 months; range, 9-97 months). A significant increase in the proportion of del13q14 cells was detected (P < .0001, Wilcoxon matched pairs), and change in the percentage of deleted cells per unit of time (1 month) significantly affected the risk of treatment requirement (HR, 2.03; P 1⁄4 .016; 95% CI, 2.03-3.6; Cox regression). Although del13q14 CLL carries a good prognosis, it is clinically and biologically heterogeneous. Although prognostic impact of baseline FISH profile is controversial, our experience confirms that the percentage of deleted cells at diagnosis represents an useful prognostic parameter. Additionally, we advise FISH monitoring for a dynamic outcome estimate and to guide clinical surveillance. FUNDING SOURCES No specific funding was disclosed.