Abstract: Background and purpose: Primary central nervous system lymphoma (PCNSL) is a rare aggressive type of non-Hodgkin's lymphoma that occurs in the brain, spinal cord, meninges or eyes, without parts outside of central nervous system (CNS) involvement. Compared with other types of lymphoma, PCNSL has shorter survival time, poor prognosis and high recurrence rate. The median survival time of untreated patients is only 3 months. In recent years, studies have found that C-MYC, BCL-2, BCL-6, Ki-67 and other indicators affect the prognosis of PCNSL patients to a certain extent. Therefore, this study analyzed the effects of PCNSL-related protein expression, treatment methods and other clinical factors on the prognosis of patients, hoping to accumulate data for the clinical treatment and prognosis evaluation of the disease. Methods: In this study, we performed a retrospective analysis of the clinical data of 42 patients with primary central nervous system diffuse large B-cell lymphoma treated in the Second Affiliated Hospital of Dalian Medical University from June 2013 to May 2021, including gender, age, number of lesions, Eastern Cooperative Oncology Group (ECOG) score, serum lactate dehydrogenase (LDH), whether the lesion involves deep brain tissue, treatment plan, pathological Hans classification and C-MYC, BCL-2, BCL-6, Ki-67 and other biomarkers, combined with follow- up investigation, to understand the survival time and survival status of patients. Kaplan-Meier method and log-rank test were used to analyze the prognostic factors affecting progression-free survival (PFS) and overall survival (OS). COX regression model was used in multivariate analysis. Results: The median age of onset in 42 patients with PCNSL was 61 years, and the male to female ratio was 1.33:1.00. Most of the brain-enhanced magnetic resonance imaging (MRI) lesions showed homogeneous and obvious enhancement. All patients received chemotherapy with high-dose methotrexate (HD-MTX) regimen. After treatment, there were 20 cases of complete response (CR), 5 cases of partial remission (PR), 11 cases of stable disease (SD) and 6 cases of progressive disease (PD). The median PFS was 21 months, the median OS was 34 months, the 1-year PFS rate was 63.7%, the 2-year PFS rate was 47.0%, the 1-year OS rate was 70.8%, and the 2-year OS rate was 55.6%. Univariate analysis showed that the factors affecting PFS were HD-MTX multidrug combination chemotherapy, intrathecal chemotherapy and combined rituximab. The factors affecting OS were ECOG score ≥2, C-MYC (+), BCL-2 and C-MYC double expression, HD-MTX multidrug combination chemotherapy, intrathecal chemotherapy and combined rituximab. Multivariate analysis showed that rituximab treatment was an independent prognostic factor for PFS (P=0.020), while ECOG score and rituximab were independent prognostic factors for OS (P=0.007, P=0.046). The median PFS and OS of patients receiving consolidation therapy were higher than those of patients without consolidation therapy, and further subgroup analysis showed that the median PFS and OS of autologous stem cell transplantation (ASCT) group were higher than those of whole brain radiotherapy (WBRT) group, however there was no significant statistical difference. Conclusion: PCNSL occurs mostly in middle-aged and elderly people, more men than women without specific imaging characteristics. ECOG score ≥2 is associated with poorer OS in PCNSL patients. C-MYC (+) and dual expression of BCL-2 and C-MYC can be used as prognostic markers to guide risk stratification. HD-MTX-based multidrug combination chemotherapy has become the first choice for the treatment of PCNSL, and the application of rituximab can prolong survival. Systemic chemotherapy combined with local intrathecal chemotherapy can improve the prognosis. Further consolidation treatments mainly include ASCT and WBRT, which can prolong PFS and OS. ASCT can achieve similar curative effects as WBRT and avoid the late neurotoxicity of WBRT. However, due to the limitations of sample size and follow-up time, no clear statistical results have been obtained in this study.

Key words: Primary central nervous system lymphoma/PCNSL, Diffuse large B-cell lymphoma, Chemotherapy, Prognosis