Immunoglobulin heavy chain variable region (IGHV) mutational status has been an important prognostic factor for chronic lymphocytic leukemia (CLL) for decades. Patients with unmutated IGHV (≥98% identity to the germline sequence) have inferior prognosis and tend to carry unfavorable genetic markers compared to those with mutated IGHV K E Y W O R D SChinese, chronic lymphocytic leukemia, cutoff value, immunoglobulin heavy chain variable region, prognosis

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Previous studies showed that, in chronic lymphocytic leukemia (CLL) patients with isolated 13q deletion (13q-), those carrying higher percentage of leukemic cells with 13q- had more aggressive diseases. However, the prognostic value of the percentage of leukemic cells with 13q- in Chinese CLL patients with isolated 13q- remained to be determined. Using interphase fluorescence in situ hybridization (FISH), we identified 82 patients (25.4%) with isolated 13q deletion from a cohort of 323 untreated CLL patients. Among patients with isolated 13q deletion, cases of 13q- cells ≥ 80% (13q-H) had significantly shorter time to first treatment (TTT) than those of < 80% 13q- cells (13q-L) (median 11 vs. 92 months, p = 0.0016). A higher lymphocyte count (p = 0.0650) was associated with 13q-H, while other clinical, immunophenotypic, or molecular features did not differ between patients with 13q-H and 13q-L. Although 13q-H only showed marginal significance in multivariate analysis of TTT (hazards ratio 2.007; 95% confidence interval 0.975-4.129; p = 0.059), it helped refine the risk stratification based on Binet stage or immunoglobulin heavy chain variable gene (IGHV) status. In cases in Binet A or B stage, patients with 13q-H had a significantly shorter TTT (median TTT 18 months vs. undefined, p = 0.0101). And in IGHV mutated patients, 13q-H was also associated with reduced TTT (median TTT 13q-H. 18 months vs. 13q-L undefined, p = 0.0163). In conclusion, the prognosis of CLL patients with isolated 13q deletion was heterogeneous with 13q-H identifying patients with worse outcome.