High Thymidine Kinase Activity and CD5 Positivity Predict Poor Prognosis Of DLBCL Treated With R-CHOP
Authors: Suzuki Kazuhito , Terui Yasuhito , Yokoyama Masahiro , Nishimura Noriko , Tsuyama Naoko , Takeuchi Kengo , Usui Noriko , Aiba Keisuke , Hatake Kiyohiko 
Published: October 2019

Abstract

Introduction
Thymidine kinase (TK) activity has been investigated as a prognostic factor in hematological malignancies, and several studies have demonstrated that high TK activity correlates with the disease stage and provides prognostic information on overall survival (OS) and progression-free survival (PFS). We have reported that high thymidine kinase activity (TK) predicts poor prognosis for diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. In addition, CD5 positivity was reported as a poor predictor for DLBCL. The purpose of this retrospective study was to investigate the prognostic value of high TK activity and CD5 positivity compared with other laboratory findings in evaluating OS in patients undergoing R-CHOP for previously untreated DLBCL.

Methods
We retrospectively analyzed 176 patients newly diagnosed with DLBCL and treated with R-CHOP from September 2003 to October 2008 in our institute, and followed them until December 2012. The values of TK activity, CD5, non-germinal center type, C-reactive protein, lactate dehydrogenase, and beta2 microglobulin before R-CHOP were evaluated as prognostic factors for overall survival (OS). The cut-off of TK activity was defined as 14 IU/L because the median level of TK activity was 14.0 IU/L. CD5 positivity was defined if CD5 expression was detected by flow cytometry. Excluded were those positive for cyclin D1 or those with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma. Germinal center type was defined by Hans classifier. The primary endpoint was OS. First, the OS and PFS were analyzed by the Kaplan-Meier method, and biological prognostic factors for OS were evaluated by Cox regression analysis. Second, we classified the patients into three risk groups due to significant poor predictors. All reported p-values were two-sided, and statistical significance was defined as p < 0.05.

Results
Median age of the evaluable patients was 65.2 years old. The number of CD5+ patients was 19 (10.8%). The median levels of TK activity, CRP, LDH, and Hb were 14.0 IU/L (range, 3.0–1,100), 0.3 IU/L (range, 0.1–21.2), 254.5 IU/L (range, 111.0–44,432), and 13.1 g/dL (range, 7.7–17.0), respectively. Median follow-up was 60.0 months. Five-year OS rate of all patients was 51.1%. The OS was significantly worse in patients with high TK activity, CD5 positivity (CD5+), and high beta2 microglobulin level by univariate analysis. Five-year OS rates of the high-TK-activity arm and the low-TK-activity arm were 39.1% and 62.9%, respectively (p = 0.001). Five-year OS rates of the CD5+ arm and the CD5-negative arm were 21.1% and 53.8%, respectively (p = 0.002). The OS was significantly worse in patients with high TK activity and CD5+ by Cox regression analysis (hazard ratios 2.595 and 2.585; p = 0.044 and 0.026, respectively). We classified the patients into three groups based on the numbers with high TK activity and CD5+. There was a significant difference of OS in the three risk groups: five-year OS rates were 8.3% in the high-risk arm (two factors), 43.9% in the intermediate-risk arm (one factor), and 64.6% in the low-risk arm (zero factors) (p < 0.001). This prognostic model was suitable for PFS. Five-year PFS rates were 8.3% in the high-risk arm (two factors), 31.7% in the intermediate-risk arm (one factor), and 59.6% in the low-risk arm (zero factors) (p < 0.001). According to the chi square test and Fisher's exact test, there was no significant relationship between high TK and CD5+ (p = 0.153).

Conclusions
High TK activity and CD5+ were strong predictors of short OS in patients with newly diagnosed DLBCL treated with R-CHOP.

Disclosures:
No relevant conflicts of interest to declare.