Background  Primary central nervous system lymphoma (PCNSL) is a rare intracranial tumor, which often histologically presents as diffuse large B-cell lymphoma (DLBCL). At present, the prognostic factors are still unclear.

  Objective  To explore the related factors of survival and prognosis by retrospectively analyzing the clinical data about 57 patients with newly diagnosed PCNSL.

  Methods  A total of 57 patients newly diagnosed with PCNSL-DLBCL in the First Medical Center of Chinese PLA General Hospital from July 2014 to January 2021 were included, and the follow-up ended in July 2022. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the prognosis and associated factors.

  Results  The median age of the 57 PCNSL patients was 55 years (range: 16 to 86 years), including 34 males and 23 females. The median progression-free survival (mPFS) was 34 months, and the median overall survival (mOS) was 57 months. The 2-year PFS and OS rates were 49% and 65%, respectively. The 5-year PFS and OS were 35% and 48%, respectively. Cox regression analysis showed that serum lactate dehydrogenase (LDH) level (HR=4.678, 95% CI: 1.572-13.925, P=0.006), with rituximab chemotherapy (HR=0.477; 95%CI: 0.207-0.926; P=0.042), multiple lesions (HR=3.369; 95%CI: 1.578-7.190; P=0.002), operation methods (needle biopsy + surgery + HD-MTX vs surgery alone: HR= 0.178, 95%CI: 0.058-0.544, P=0.002; S + HD-MTX vs surgery alone: HR= 0.153, 95%CI: 0.050-0.467, P=0.001) and with allogeneic stem cell transplantation (ASCT) (HR=0.102, 95%CI: 0.013-0.794, P=0.029) were associated with PFS. Eastern Cooperative Oncology Group (ECOG) score ≥2 (HR=3.121, 95% CI: 1.192-8.170, P=0.020), multiple lesions (HR= 2.714, 95%CI: 1.076-6.846, P=0.034), operation methods (needle biopsy + surgery + HD-MTX vs surgery alone: HR=0.127, 95% CI: 0.034-0.471, P=0.002; surgery + HD-MTX vs surgery alone: HR=0.070, 95% CI: 0.018-0.269, P<0.001), and with ASCT (HR= 0.138, 95%CI: 0.017-0.941, P=0.046) were associated with OS. However, there was no significant difference in the survival prognosis between the patients who received comprehensive treatment after biopsy and surgical resection (P>0.05).

  Conclusion  Patients with elevated serum LDH, ECOG score ≥2, and multiple lesions before PCNSL-DLBCL treatment have poor prognosis. High-dose methotrexate-based combined chemotherapy regimen after needle biopsy should be the first choice for treatment. The addition of rituximab during induction therapy can significantly improve survival, and ASCT during consolidation therapy should be prioritized.