继发性中枢神经系统淋巴瘤24例临床分析

Clinical Features and Treatment Outcomes of Secondary Central Nervous System Lymphomas

目的继发性中枢神经系统淋巴瘤(SCNSL)是非霍奇金淋巴瘤(NHL)继发播散累及到中枢神经系统(CNS)。SCNSL发病率低且预后较差,目前还没有标准的预防及治疗方法。方法为了进一步了解SCNSL的临床特征和预后,我们回顾性分析了我院2018年1月1日至2022年7月30日收治的24例SCNSL患者的临床特征。结果24例SCNSL患者的肿瘤组织类型包括17例(70.83%)弥漫性大B细胞淋巴瘤(DLBCL),5例(20.83%)惰性B细胞淋巴瘤,1例(4.17%)外周T细胞淋巴瘤-非特指型淋巴瘤,1例(4.17%)原发纵隔大B细胞淋巴瘤。我们主要关注17例SCNSL(DLBCL)患者的临床特征。起病方式:12例(70.59%)SCNSL(DLBCL)患者为起病时CNS及CNS外同时受累;5例(29.41%)SCNSL(DLBCL)患者为NHL进展时单独CNS受累,而没有同时合并CNS外病灶。病理亚型:13例(76.47%)为非生发中心B细胞来源(non-GCB)亚型。基因分型:11例患者的肿瘤组织进行了二代测序,9例(81.82%)患者的分子亚型为MCD亚型。诊治过程:16例SCNSL(DLBCL)患者一线接受了利妥昔单抗联合大剂量甲氨蝶呤(R-HD-MTX)为基础的治疗,1例患者因脑出血未接受治疗而死亡。转归:16例患者中6例(37.5%)患者经一线治疗达到PR或CR,其他10例患者(62.5%)一线治疗后SD或者PD,二线方案包括放疗、BTK抑制剂、免疫调节剂及其他二线方案化疗。该组患者中位随访时间为13(3~35)个月,10例(58.8%)患者存活,7例(41.2%)患者因疾病进展死亡,包括4例患者的中枢病灶进展和2例患者的全身病灶进展,1例因化疗中消化道大出血死亡。17例SCNSL(DLBCL)患者的平均生存期(overall survival,OS)为23.2±3.5个月,3年预计OS为0.3;平均PFS为13.4±2.6个月,3年预计为0.19。结论在这项回顾性研究中,DLBCL为SCNSL中主要的病理类型,病理亚型以non-GCB,双表达为著,分子亚型多为MCD亚型,这组患者预后较差,多数起病时存在中枢及中枢外病灶,R-HD-MTX-CHOP方案疗效不佳,一线使用BTK抑制剂联合化疗或BTK药物维持治疗有望提高这部分患者的疗效和生存质量。

Objective Secondary central nervous system lymphoma(SCNSL)is a malignant lymphoma with secondary central nervous system involvement.SCNSL is a rare condition with currently no standard treatment.Methods To clarify the clinical features and outcomes of SCNSL,we retrospectively analyzed 24 patients in Xuanwu Hospital for the past 3 years.Results 24 cases of patients with SCNSL were selected for the study,including 17(70.83%)cases of diffuse large B cell lymphoma(DLBCL),5(20.83%)cases of indolent B-cell lymphoma,B cell lymphoma,1(4.17%)case of peripheral T cell lymphoma-Non-specific type(PTCL-NOS),and 1(4.17%)case of primary mediastinal large B cell lymphoma(PMBCL).We mainly focused on the clinical features of 17 patients with SCNSL originating from DLBCL.Modes of onset were as following:12(70.59%)patients had CNS and extra-CNS involvement at onset;when NHL progressed,5(29.41%)patients with SCNSL(DLBCL)had only CNS involvement without concurrent involvement of extra-CNS lesions.Hans classification was as following:13 cases(76.47%)as a source of germinal center B cell subtype(non-GCB).Characteristics of tumor tissue next-generation sequencing(NGS)were as following:11 patients underwent NGS examination,and 9(81.82%)patients had the molecular subtype of MCD subtype.Treatments were as following:16 patients received first-line treatment based on rituximab combined with high-dose methotrexate(R-HD-MTX),and 1 patient died of cerebral hemorrhage without further treatment.Results Among the 16 SCNSL(DLBCL)patients,6 patients(37.5%)achieved PR or CR,10 patients(62.5%)achieved SD or PD after first-line treatment.Second-line regiments included radiotherapy,BTK inhibitors,immunomodulators and other second-line chemotherapy.The median follow-up time of our study was 13 months(3-35 months),during which 10 patients(58.8%)survived,7 patients(41.2%)died due to disease progression,including 4 patients with central lesion progression and 2 patients with systemic lesion progression,and 1 patient died due to massive gastrointestinal bleeding during chemotherapy.The mean overall survival(OS)of 17 patients with SCNSL(DLBCL)was 23.2±3.5 months,and the estimated OS at 3 years was 0.3.The mean PFS was 13.4±2.6 months and the 3-year forecast was 0.19.Conclusion In this retrospective study,DLBCL non-GCB MCD is the main pathological type in SCNSL.This group of patients has a poor prognosis and remains as challenges in the current SCNSL treatment.BTK drug maintenance therapy or first-line use of BTK inhibitors in combination with chemotherapy is expected to improve outcomes and survival in these patients.