High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome

Abstract

We have analyzed patients with previously untreated chronic lymphocytic leukemia with del11q fluorescence in situ hybridization (FISH) abnormality (n = 196) in this study. Detection of the 11q22.3 used a multicolor FISH technique. Patients with del11q fell into two major FISH subsets-sole del11q (n = 64) and del11q with del13q (n = 132). FISH subsets were compared using the median del11q FISH% (>58%, high vs. ≤58%, low). Overall survival (OS) and time to first treatment (TTFT) were estimated using Kaplan-Meier plots (log rank). Multivariate analysis was performed to assess the association between FISH% of del11q and outcomes. Patients with sole del11q were similar to del11q with del13q in terms of TTFT and OS. Patients with high FISH% of del11q had significantly shorter OS and TTFT as compared with patients with low FISH%, particularly in sole del11q; this negative impact of high FISH% of del11q on OS and TTFT was diminished with coexistent del13q. In multivariate analysis, high FISH% of del11q was a significant predictor for shorter OS and TTFT. A comparison of these del11q subsets with a separate cohort of (n = 673) previously untreated patients with sole del13q showed that the high FISH% del11q cohort had a significantly shorter TTFT and OS. In addition, bulky disease by physical examination or computed tomography imaging was infrequent at presentation in patients with del11q. High FISH% of del11q can reliably discriminate higher risk patients with chronic lymphocytic leukemia. Presence of coexistent del13q should be accounted for while prognosticating patients with del11q.

Figure 1

(A–C) Analysis of time to first treatment (TTFT) in previously untreated CLL patients with del11q FISH subsets (sole del11q and del11q with del13q, n = 64 and n = 132, respectively) and median FISH% del11q. (A) Median TTFT was 4.5 and 10.3 months in sole del11q and del11q with del13q, respectively, and was not significantly different (P = 0.56). (B) Median TTFT was significantly shorter in patients with high FISH% (>58%) as compared with those with low FISH% (≤58%) in sole del11q: 1.7 vs. 19.1 months (P = 0.02). (C) Based on FISH%, TTFT was not significantly different among patients with del11q with del13q (P = 0.12). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

(A–C) Analysis of impact of coexistent del13q on overall survival (OS) in previously untreated CLL patients with del11q FISH subsets (sole del11q and del11q with del13q, n = 64 and n = 132, respectively). (A) Median OS was not reached (NR) in either group (P = 0.45). (B) Median OS was significantly shorter in patients with high FISH% (>58%) as compared with those with low FISH% (≤58%) in sole del11q: NR months vs. NR (P = 0.02). (C) Based on FISH%, OS was not significantly different among patients with del11q with del13q (P = 0.25). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

(A–F) Comparison of TTFT and OS among del11q FISH subsets (sole del11q and del11q with del13q) with a cohort of untreated CLL patients with sole del13q (n = 673). Time to first treatment (TTFT) is compared among sole del11q (n = 64), del11q with del13q (n = 132), and sole del13q (n = 673). (A) Median TTFT was significantly shorter in del11q FISH subsets compared with sole del13q cohort: 4.5, 10.3, and 73.5 months, respectively (P < 0.0001). (B, C) Median TTFT was significantly shorter in del11q FISH subsets as compared with sole del13q, with respect to FISH%. Subgroup of patients with high FISH% (>58% for del11q subsets and >50.5% for sole del13q) and low FISH% (≤58% for del11q categories and ≤50.5% for sole del13q) are shown (P < 0.0001 for high and low FISH% subgroups). (D) OS was significantly different among the three groups (sole del11q, del11q with del13q, and sole del13q). Median OS was not reached (NR) in all the three groups (P = 0.04). (E, F) Median OS was significantly shorter in sole del11q with high FISH% when compared with coexistent del13q and sole del13q with high FISH% (P = 0.002). Within low FISH% patients, OS was not significantly different among the three groups (P = 0.13). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]