Treatment Outcome and Prognostic Factors of Korean Patients with Chronic Lymphocytic Leukemia: Multicenter Retrospective Study

Backgrounds: The incidence of chronic lymphocytic leukemia (CLL) in Asian population is very low, while CLL is the most common type of leukemia in Western countries. Asian CLL has been reported to have different immunophenotypes and clinical outcomes compared to those of western CLL. But, data on CLL in Asian countries is very limited because of the disease rarity. Thus, we evaluated the clinical characteristics and treatment outcome of Korean CLL patients and also analyzed prognostic significance of clinical parameters.

Methods: We retrospectively analyzed 73 newly diagnosed CLL patients who had received chemotherapy at the 5 centers in Korea between 2000 and 2012. The CLL diagnosis and response evaluation were based on the International Workshop on CLL criteria updated in 2008. Small lymphocytic lymphoma was excluded in this study.

Results: The median age of all patients was 60 years (range, 25-93 years). Compared to Western data, the positivity of atypical immunophenotypic markers such as CD 22 and FMC7 were frequently observed (45.5% and 69.2% of evaluable patients, respectively). As the first line chemotherapy, the various regimens were used as followings: chlorambucil (n=45), fludarabine (n=13), fludarabine, cyclophosphamide, and rituximab (FCR) (n=4), cyclophosphamide, vincristine, and prednisolone (CVP) (n=4), fludarabine and cyclophosphamide (FC) (n=3), and the other regimens (n=4). Patients were at Binet A (49.3%), B (11.6%) with active disease or stage C (39.1%) at the time of chemotherapy. The overall response rate after the first line chemotherapy was 69.9% with the complete remission (CR) rate of 15.1%. The FCR regimen achieved the highest CR rate (50%). Fifty patients were treated with the second line chemotherapy. Two patients received allogeneic hematopoietic stem cell transplantation at the refractory state and they are still alive without relapse. Of all included patients, the probability of overall survival (OS) and progression free survival (PFS) at 5-years was 84.9% and 28.7%, respectively. The 5-year relapse free survival (RFS) rate of the 17 patients attaining CR was 42.4%. Univariate and multivariate analyses showed that the higher WBC count (>100x10³/¥ìL), the lower platelet count (<80x10³/¥ìL), and the constitutional symptoms had a significantly adverse impact on OS (hazard ratio [HR], 6.584, p=0.002; HR, 15.692, p<0.001; HR, 4.769, p=0.010, respectively) (Table 1). The platelet count between 80x10³/¥ìL and 110x10³/¥ìL, however, had no prognostic significance. Compared to the kappa type of immunoglobulin light chain, the presence of lambda type on leukemic cells was a significant negative prognostic factor for PFS (HR, 2.775, p=0.037), although there was no significant difference on OS. The CR achievement after the second line chemotherapy or more was significantly related to shorter RFS (HR, 7.343, p=0.021) compared to that of the CR achievement after the first line chemotherapy.

Conclusion: Thrombocytopenia (<80x10³/¥ìL) is the most significant prognostic factor predicting worse survival in Korean CLL patients. In addition, hyperleukocytosis (>100x10³/¥ìL), constitutional symptoms, and the lambda type of light chain restriction need to be reflected into the risk stratification system for CLL.

Keywords: chronic lymphocytic leukemia, outcome, prognostic factor

WBC, white blood cell; CR1, complete remission after 1^st line chemotherapy; CR2, complete remission after 2^nd line chemotherapy; CR3, complete remission after 3^rd line chemotherapy; Allo-HCT, allogeneic hematopoietic stem cell transplantation