Development of a Novel Prognostic Scoring System of Time to First Treatment for Chinese Patients with Chronic Lymphocytic Leukemia

Background: The established clinical staging systems (Rai/Binet) of chromic lymphoma leukemia (CLL) had limitedly discriminated among prognostic groups, especially for the patients in early stages and without treatment indications. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated the prognostic improvement of the combination of more markers together. In order to predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional bio-markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index.

Patients and Methods: Taking advantage of a population of 402 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months (ms). Multivariable statistics were applied with software SPSS 17.0, and the end point was TTFT.

Results: Based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (Rai risk group), 17p deletion and unmutated IGHV. Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups [low risk (score 0), intermediate low (score 1), intermediate high (score 2) and high risk (score 3-6)] with significantly different TTFT (median TTFT of NR, 65.0 ms, 36.0 ms and 19.0 ms, respectively, p<0.001).

Conclusions: This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers (IGHVmutation status, 17p deletion) with traditional clinical stage (Rai staging system). This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.