继发性中枢神经系统淋巴瘤预防与诊治研究进展

Research progress on the prevention,diagnosis and treatment of secondary central nervous system lymphoma

目的总结弥漫大B细胞淋巴瘤(DLBCL)继发性中枢神经系统(CNS)累及的预防与诊治进展,以提高对该病的认识。方法应用PubMed、万方数据库等检索,以"继发性中枢神经系统淋巴瘤、中枢神经系统淋巴瘤、预防、治疗、诊断、自体造血干细胞移植"为检索词,检索1990年1月-2020年5月发表的相关文献。纳入标准:与继发性中枢神经系统淋巴瘤(SCNSL)的预防与诊治有关的文献。排除标准:研究资料缺失。根据上述标准,最终共纳入分析53篇,其中英文文献50篇,中文文献3篇。结果对继发性CNS受累的风险评估主要根据"CNS-IPI"模型,而将细胞起源与其结合提出"CNS-IPI-C"模型,为预测CNS复发风险提供了新的思路,但尚未普遍应用于临床。临床实践中予以CNS预防的范围相对宽泛,主要为鞘内或静脉应用甲氨蝶呤。诊断需要结合临床症状、影像学检查、脑脊液细胞学和流式细胞学检查及病理组织学检查结果进行综合判断。对于SCNSL的治疗需要同时兼顾CNS及系统性受累病灶,目前以基于大剂量甲氨蝶呤的联合化疗为主,放疗主要作为辅助治疗,大剂量化疗联合自体造血干细胞移植可作为复发/难治甚至是老年患者的选择,但最佳治疗方案尚未达成共识。来那度胺、培美曲塞、依鲁替尼等药物均可改善患者预后,但临床证据尚且不足。新的靶点药物及治疗方法有待进一步研究。结论对SCNSL的诊断需要综合判断,治疗以基于大剂量甲氨蝶呤的联合化疗为主。随着新型药物的研发和治疗方法的改进,相信未来SCNSL患者的预后将得到较大的改善。

Objective Secondary central nervous system lymphoma(SCNSL) refers to the involvement of brain parenchyma, spinal cord, eye, cerebral nerves or meninges on the basis of systemic lymphoma,and it was an aggressive disease with unfavourable prognosis. This article reviewed the research progress of prevention, diagnosis and treatment of secondary nervous system(CNS) infiltrated by diffuse large B-cell lymphoma(DLBCL),so as to enhance the knowledge of this disease. Methods "secondary central nervous system lymphoma, central nervous system lymphoma, prevention, treatment, diagnosis, autologous hematopoietic stem cell transplantation etc. " were searched as key words by PubMed and Wanfang series full-text data-base retrieval system from January,1990 to May,2020. The inclusion criteria: articles about the prevention, diagnosis and treatment of secondary central nervous system lymphoma. Exclusion criteria: lack of research data. According to the criteria above, a total of 53 articles were finally included in the analysis, including 50 English papers and 3 Chinese papers. Results The assessment of the risk of secondary CNS involvement is mainly based on the "CNS-IPI" model,and the "CNS-IPI-C" model proposed by combining the origin of cells with "CNS-IPI" model provides inspiration for predicting the risk of CNS recurrence, but it has not been widely applied to clinical practice. The application of CNS prevention in clinical practice is relatively broad, and prophylactic measures include intrathecal or intravenous administration of methotrexate. Diagnosis is mainly based on the comprehensive judgment of symptoms of central nervous system involvement, imaging examinations, cerebrospinal fluid cytology, flow cytometry, and histopathological examinations. The treatment of SCNSL needs to take both the CNS and systemic lesions into account. High-dose methotrexate-based chemotherapy has become the main therapeutic regimen of SCNSL. Radiotherapy is mainly used as an auxiliary treatment. High-dose chemotherapy followed by autologous stem cell transplantation can be an option for relapsed/refractory and even elderly patients. Even so,the best therapeutic regimen has not yet reached a consensus. Drugs such as lenalidomide, pemetrexed, and ibrutinib can improve the prognosis of patients, but the clinical evidence is still insufficient. New target drugs and treatment methods need to be further studied. Conclusions The diagnosis of SCNSL requires comprehensive judgment. High-dose methotrexate-based chemotherapy regimens are the mainstay of treatment. With the development of new drugs and treatment methods, it is believed that the prognosis of SCNSL patients will be greatly improved in the future.