CXCL13 is prognostic and mediates chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. (A) Survival for the cohort of PCNSL patients by International Extranodal Lymphoma Study Group score (N = 33 total patients), demonstrating representation of the prognostic subgroups. Kaplan-Meier analysis; y-axis indicates percent overall survival (OS). The International Extranodal Lymphoma Study Group prognostic score is based on 5 variables: age >60, Performance Status >1, elevated lactate dehydrogenase, elevated CSF protein, and involvement of deep regions in the brain. (B) Newly diagnosed patients with PCNSL (N = 34 patients) with elevated CXCL13 at diagnosis (>200 pg/mL, the median CSF concentration among all CNS lymphoma patients) exhibited shorter time to progression (TTP) after treatment with methorexate-based induction. P < .01 (hazard ratio = 2.96). The median TTP of PCNSL patients with low CSF CXCL13 (N = 16) is 82 months vs 7 months for patients who presented with elevated CSF CXCL13. (C) PCNSL and SCNSL (N = 41) with elevated CSF CXCL13 at diagnosis exhibit shorter PFS (defined as disease progression or death as a result from any cause).²¹ P < .005 (hazard ratio = 3.12). The median PFS of PCNSL and SCNSL patients with low CSF CXCL13 (N = 19) is 82 months vs 9 months for patients who presented with high CXCL13. The OS of PCNSL and SCNSL patients with low CSF CXCL13 at diagnosis is also longer than for patients with high CSF CXCL13 at diagnosis. P < .04 (hazard ratio = 3.03), although the median OS for both cohorts has not been reached (not shown). All patients were treated with a high-dose methotrexate-based induction regimen without whole brain irradiation consolidation. Patients with stage IV DLBCL with CNS involvement (C) received cyclophosphamide, vincristine, adriamycin, and prednisone instead of temozolomide, as described.²⁷  (D) Directed chemotaxis of CNS lymphoma cells (isolated from a brain parenchymal lesion of relapsed CNS lymphoma) in response to chemokines CXCL13 and CXCL12. The y-axis depicts chemotaxis index (% compared with medium control). P < .05. (E) CXCL13- and CXCL12-mediated chemotaxis of meningeal lymphoma cells isolated from the CSF of a CNS lymphoma patient with refractory disease. P < .05. There was no evidence for synergy or additive effects when CXCL13 and CXCL12 were used in combination, and there was no chemotaxis in response to C3a anaphylatoxin or ephrin A4 peptides.