OS4.7 CXCL13 in cerebrospinal fluid (CSF) as a biomarker for primary central nervous system cell lymphoma (PCNSL)

Abstract

Introduction: Malignant lymphoma cells are known to secrete various cytokines and chemokines. We previously reported that the CSF level of interleukin‐10 (IL‐10) was significantly increased in primary central nervous system lymphomas (PCNSLs), as compared with other brain diseases. Recently, CXCL13 level in CSF is reported to be useful biomarker for PCNSL. We analyzed CXCL13 levels in CSF and compared CSF CXCL13 with other CSF cytokines and prognosis. Methods: Seventy‐nine CSF samples were analyzed. Twenty‐five samples were PCNSL (all diffuse larger B‐cell lymphomas), 41 samples were gliomas, 4 samples were germ cell tumors, 4 samples were multiple sclerosis, 2 samples were metastatic tumors, and 3 samples were other diseases. The CXCL13 levels were measured by ELISA. In addition, IL‐10 and IL‐6 in CSF were measured and compared with CXCL13 levels. Also, relationship between CXCL13 levels and prognosis (overall survival (OS) and progression‐ free survival (PFS)) was analyzed by Cox proportional hazards model. Results: Mean CXCL13 concentrations in CSF were 964.2 pg/ml (475.3~1481.1 pg/ml) and 54.9 pg/ml (<1~999.7 pg/ml) in PCNSLs and other brain diseases, respectively. CXCL13 levels in CSF were significantly increased in PCNSLs compared with other brain diseases (p<0.0001). At a CXCL13 cutoff level of 475 pg/ml, the sensitivity and specificity were 100 % and 98 %, respectively. CXCL13 levels were correlated with CSF IL‐10 levels (p=0.0003) and CSF IL‐6 levels (p=0.0053). Median OS and PFS in all patients with PCNSL were 36 months and 25 months, respectively. And CXCL13 levels in CSF were statistically associated with OS (p=0.02) and PFS (p=0.01) in the patients with PCNSL. Conclusion: These results indicate that the CSF CXCL13 levels are quite useful biomarker for PCNSLs. To validate a usefulness of SF CXCL13 for diagnosis of PCNSL, multicenter prospective large study is necessary.