Different Prognostic Significance of a Panel Cytogenetic Aberrations Between Chronic Lymphocytic Leukemia and Other B-Cell Chronic Lymphoproliferative Disorders

Background: B-cell chronic lymphoproliferative disorders (B-CLPD) comprise several entities with similar clinical manifestations, within which chronic lymphocytic leukemia (CLL) account for the majority, others including follicular lymphoma (FL), hairy cell leukemia (HCL), splenic marginal zone lymphoma (SMZL),nodal marginal zone lymphoma (NMZL), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM), and other unclassified subtypes. Cytogenetic aberrations are now the main prognostic predicators in CLL, with deletion of TP53 or ATM as the adverse predicators, while sole deletion of 13q14 as the favorable one, trisomy 12 and IGH translocation as the neutral factors. The prognostic role of this cytogenetic aberrations panel has not been well established in other B-CLPD excluding CLL.

Patients and methods:  A panel of DNA probes were used to detect cytogenetic aberrations by fluorescence in situ hybridization (FISH), including RB1/D13S25 at 13q14, ATM at 11q22, TP 53 at 17p13, CEP12 and IGH translocation at 14q32. Totally, 870 patients were enrolled in this study, including 459 CLL patients, 41 SMZL patients, 24 HCL patients, 96 LPL/WM patients, 24 NMZL patients with bone marrows involvement (BMI) ,59 FL patients with BMI and 161 patients without definite subtype classification.

Results: The incidence of each cytogenetic aberration in CLL is as follow: 38.0%(169/445) for del 13q14, 11.5% (46/400) for del 11q22, 14.5% (66/455) for del 17p13 , 23.8% (68/286) for +12, and 21.9% (97/443) for t(14q32). While in other B-CLPD excluding CLL is as follow: 10.3% (36/351) for del 13q14, 3.6% (11/305) for del 11q22, 7.9% (30/380) for del 17p13, 12.3% (23/ 187) for +12 and 24.1% (93/386) for t(14q32). The incidence of del 13q14 (p=.000), del 11q22 (p=.000), del17p13 (p=.003) and +12 (p=.002) were higher in CLL than in other B-CLPD.  With a median follow-up of 46.0 months (2.0-288.0) in CLL and 39 months (3.0-239.0) in other B-CLPD, the median estimated progress-free survival (PFS) and overall survival (OS) in CLL were 80.0 months (95% CI 67.2-92.7) and 129 months (95% CI 111.5-146.5)  respectively, while in other B-CLPD were 84 months (95% CI 71.8-96.1) and 135 months  respectively.

In CLL, the del 13q (p=.046), del 11q (p=.002) and del 17p (p＜.001) were the adverse predictors for the PFS with only del 17p (p＜.001) for the OS. There were no significant difference between patients with or without del 13q in aspect of OS (129.0 vs 110.5 months, p=.207). while sole del 13q was the favorable predictor for both PFS  (p＜.001) and OS (p=.001). Del 11q also indicated poor OS  without statistical significance (p=.112). The median PFS for patients with or without +12 was 90 months (95% CI 60.5-119.5) and 93.0 months (95% CI 73.3-112.7) (p=.273), and the median OS was also similar (131.0 months vs. 129.0, p=.921). IGH translocation did not significantly influence both PFS (p=.198) and OS (p=.648).

In other B-CLPD except CLL, the del 13q, del 17p and t (14q32) had no impact on both PFS (p=.983, p=.910 and p=.675 respectively) and OS (p=.171, p=.401 and p=.453 respectively). But patients with trisomy 12 had poor PFS (69.0 vs.86.0months, p=.094) and OS (69.0 vs.135.0months, p=.006) compared with those without. Del 11q also adversely impacted the OS (75.0 months vs. not reached, p=.059) but not PFS (62.0 vs. 84.0 months, p=.735).

Conclusions:  Del 11q and del 17p had the adverse prognostic impact in CLL. However, trisomy 12 was the predictor of poor survival in other B-CLPD which indicated neutral prognostic role in CLL. These results may imply different role of the same cytogenetic aberration in the pathology between CLL and other B-CLPD.