Impact of meningeal dissemination (MD) on outcome in primary CNS lymphoma in the G-PCNSL-SG1 trial.

2026 Background: The prognostic impact of MD in PCNSL is still debated. Within the framework of a multicenter randomized trial (G-PCNSL-SG1) we evaluated patients for outcome according to the presence of MD. METHODS Immunocompetent adult patients were initially treated with up to six cycles of high-dose methotrexate (HD-MTX; 4g/m2) based chemotherapy without intrathecal therapy. Those randomized to radiotherapy subsequently received whole-brain radiotherapy (WBRT) with 45 Gy, in 1.5 Gy fractions; those randomized to chemotherapy did not receive further therapy in case of complete remission or high-dose cytarabine when complete response was not achieved. MD was defined by the presence of lymphoma cells in the CSF detected by at least one of the following methods: cytomorphology, detection of clonal B cells by IgH-PCR or contrast enhancement of the leptomeninges on MRI. RESULTS All 526 patients fulfilling the eligibility criteria were entered into the analysis. MD at presentation was detected in 104 (19.8 %) patients: 95 by cytomorphology, 16 by PCR and 17 by MRI. Pretherapeutic characteristics including age, Karnofsky performance score, sex, serum lactate dehydrogenase, lymphoma localization, mode of biopsy, histology, CSF protein elevation (>45mg/dl) and ocular involvement did not significantly differ in patients with MD and other patients (all p>0.05). Only CSF pleocytosis (>5/µl) was significantly more frequent in patients with MD (37 vs. 14%, p<0.001). The type of chemotherapy (HD-MTX: 83 vs. 75%, HD-MTX and ifosfamide: 17 vs. 25%) applied and the frequency of WBRT (39 vs. 34%) were not significantly different in the group with and without MD. Median overall survival (OAS) in the MD group was 21.5 (95% CI 17.1-25.8) months as compared to 22.4 (17.3-27.5) months in other patients (p=0.8); median progression free survival (PFS) was 6.1 (1.6-10.5) and 7.0 (5.2-8.8) months, respectively (p=0.9). Median OAS and PFS were not significantly different in patients with elevated CSF protein or CSF pleocytosis compared to patients with normal CSF values. CONCLUSIONS MD, elevated CSF protein and CSF pleocytosis had no impact on outcome in this trial.