Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.
Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia.
Eur J Cancer. 2018 Apr;93:57-68. doi: 10.1016/j.ejca.2018.01.073. Epub 2018 Feb 21.
Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited.
Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records.
In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9).
In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
中枢神经系统(CNS)继发受累是弥漫性大 B 细胞淋巴瘤的一种严重不良并发症。来自于旧系列的数据显示中位总生存期(OS)<6 个月;然而,免疫化疗时代的数据有限。
从三个大洲的数据库和/或区域/国家登记处确定了一线免疫化疗期间或之后发生 CNS 继发受累的患者。临床信息从病历中回顾性收集。
共纳入 291 例 CNS 继发受累患者。254 例(87%)患者的 CNS 继发受累发生在首次复发时,113 例(39%)患者同时存在全身复发。在 CNS 继发受累后中位随访 48 个月时,中位 CNS 继发后 OS 为 3.9 个月,2 年 OS 率为 20%(95%CI:15-25)。在对 173 例接受根治性/强化治疗(如大剂量甲氨蝶呤[HDMTX]或含铂方案)的患者进行多变量分析时,年龄≤60 岁、体能状态 0-1 分、无脑膜和实质合并受累以及 CNS 继发受累发生在一线治疗完成后与更好的结果相关。年龄≤60 岁、体能状态 0-1 分且接受 HDMTX 为基础方案治疗孤立性实质 CNS 继发受累的患者 2 年 OS 率为 62%(95%CI:36-80)。在孤立性 CNS 继发受累且达到缓解的患者中,HDMTX 为基础方案联合利妥昔单抗治疗可改善 OS。在接受强化治疗后达到完全缓解的孤立性 CNS 继发受累患者中,大剂量化疗和自体造血干细胞移植并不能改善 OS(P=0.9)。
在本项来自于一线免疫化疗的大型国际患者队列研究中,CNS 继发受累后的结局仍然较差。然而,相当一部分接受强化治疗的孤立性 CNS 继发受累患者获得了持久缓解。