Yuan Yan, Ding Tianling, Wang Shu, Chen Hong, Mao Ying, Chen Tong
Department of Hematology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Department of Pathology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Biomark Res. 2021 May 6;9(1):32. doi: 10.1186/s40364-021-00282-z.
Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.
原发性中枢神经系统（CNS）淋巴瘤（PCNSL）是一种罕见的结外淋巴瘤，起病时仅累及中枢神经系统，弥漫性大B细胞淋巴瘤（DLBCL）是最常见的组织学亚型。由于PCNSL是在免疫豁免部位发生的恶性肿瘤，全身药物向肿瘤组织的递送欠佳导致PCNSL的预后比非中枢神经系统DLBCL更差。PCNSL常用的治疗方案包括以大剂量甲氨蝶呤为基础的化疗联合利妥昔单抗进行诱导治疗，以及强化化疗后行自体造血干细胞移植或全脑放疗进行巩固治疗。针对B细胞受体信号通路、微环境免疫调节和血脑屏障（BBB）通透化的靶向药物在治疗难治性/复发性患者方面似乎很有前景。嵌合抗原受体T细胞（CAR-T细胞）已被证明可穿透血脑屏障，作为一种潜在工具来治疗这种疾病实体，同时控制与CAR-T细胞相关的脑病综合征。未来的治疗方法可能会根据年龄、体能状态、分子生物标志物和细胞生物信息对患者进行分层。本综述总结了目前PCNSL治疗的临床疗法和正在临床开发中的新兴药物。
