Prognostic Factors of Chinese Patients with Chronic Lymphocytic Leukemia.

Abstract 4387

Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in the Western countries, however, infrequent in Asian populations. Although the median survival is around 10 years, CLL is a disease with an extremely variable clinical course with overall survival times ranging from months to decades; some patients never need treatment, while others require intensive treatment early after diagnosis. Some factors, such as clinical stages, IGHV mutational status, cytogenetic abnormalities, ZAP-70, and the expression of CD38 in leukaemic cells, were strong indicator of prognosis in CLL. However, the prognostic factors of Chinese patients with CLL compared with the Western countries have not yet been clarified. The aim of this study was to explore the influence of factors on the prognosis of Chinese patients with CLL. One hundred and twenty-nine patients with CLL were enrolled in this study. Multiplex PCR and sequencing, fluorescence in situ hybridization (FISH), and flow cytometry were used to detect IGHV mutational status, cytogenetic abnormalities, and the expression of ZAP-70 and CD38, respectively. A panel of FISH probes included 13q14 (D13S319), 17p13 (p53 gene), 11q23 (ATM gene), 6q23(MYB gene), the centromere of chromosome 12 (D12Z3) and 14q32 (IGHC/IGHV). In 129 CLL patients, according to the Binet clinical staging system, 65 (50.4 %) patients were in Binet A, 28 (21.7 %) in Binet B and 36 (27.9 %) in Binet C. Eighty-four (65.1%) patients had mutated IGHV, and 45 (34.9%) had unmutated IGHV. The most frequently expressed VH gene family was found to be VH3 (50.4%) followed by VH4 (32.6%), VH1 (10.9%), VH2 (2.3%), VH5(2.3%) and VH7 (1.6%), with no expression of VH6 gene families. VH1-69 and VH3-21 which commonly overused in Western CLL patients were very low in our cohort (0.8% and 3.1%, respectively). Molecular cytogenetic aberrations were found in 94 patients (72.9%) and 36 patients (27.9%) with more than two abnormalities. The most frequent abnormalities detected in our patients was del(13q14), with an incidence of 53.0%, followed by 14q32 translocation of 20.2%, +12 of 18.3%, del(11q23) of 10.8%, del(17p13) of 10.o%, and del(6q23) of 6.1%. Forty-one patients (31.8%) were positive for ZAP-70 (≥20%), and 51 patients (39.5%) were positive for CD38 (≥30%). With a median follow-up of 32 months (range, 4-58 months), eight patients (6.2%) died (CLL-related deaths). In univariate analysis for survival, advanced Binet stage (P=0.023), unmutated IGHV status (P=0.002), deletions of 17p13 or 11q23 (P=0.003), high expression of ZAP-70 (P=0.034), and high expression of CD38 (P=0.046) were poor prognostic factors. The prognostic factors with statistical significance were further used in a two-variables Cox analysis, which comparing unmutated IGHV status to other prognostic factors individually to show prognostic independence. The unmutated IGHV status were the independent prognostic factors and strongly associated with OS. This study demonstrates that the frequencies of IGHV gene families indicated significant difference in Chinese CLL patients compared with Western patients, suggesting involvement of ethnic and/or environmental factors in CLL disease initiation. The unmutated IGHV status, Binet clinical stages, Chromosomal aberrations of del(17p13) and del(11q23), high expression of ZAP-70 and CD38 have been shown highly predictive prognostic value for Chinese patients with CLL.