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结外弥漫性大 B 细胞淋巴瘤部位与 R-CHOP 化疗耐药和早期复发的风险。

Extranodal site of diffuse large B-cell lymphoma and the risk of R-CHOP chemotherapy resistance and early relapse.

机构信息

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Int J Clin Pract. 2020 Oct;74(10):e13594. doi: 10.1111/ijcp.13594. Epub 2020 Jul 14.

Abstract

BACKGROUND

About 20%-30% of diffuse large B-cell lymphoma (DLBCL) patients experience early disease progression despite R-CHOP chemotherapy treatment. Revised international prognostic index (R-IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R-CHOP therapy or experience early relapse.

AIMS OF THE STUDY

To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment.

METHODS USED TO CONDUCT THE STUDY

A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group.

RESULTS OF THE STUDY

81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05).

CONCLUSION AND CLINICAL IMPLICATIONS

DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

摘要

背景

尽管接受 R-CHOP 化疗治疗,仍有约 20%-30%的弥漫性大 B 细胞淋巴瘤(DLBCL)患者发生早期疾病进展。修订后的国际预后指数(R-IPI)评分可对 DLBCL 患者进行风险分层,但无法明确指出哪些患者对 R-CHOP 治疗有耐药性或会发生早期复发。

研究目的

分析 R-CHOP 治疗后发生耐药和早期复发的 DLBCL 患者的治疗前临床特征。

研究方法

对 698 例淋巴瘤患者进行筛选,纳入 134 例接受 R-CHOP 治疗的 DLBCL 患者。采用卢加诺 2014 标准评估治疗反应。将 DLBCL 患者分为 R-CHOP 耐药/早期复发组和 R-CHOP 敏感/晚期复发组。

研究结果

134 例患者中,81 例(60%)为 R-CHOP 敏感/晚期复发,53 例(40%)为 R-CHOP 耐药/早期复发。中位随访时间为 59 个月±标准误差 3.6。R-CHOP 耐药/早期复发组的 5 年总生存率为 2.1%,而 R-CHOP 敏感/晚期复发组为 89%。DLBCL 患者存在一个以上结外部位为 R-CHOP 耐药/早期复发的独立危险因素[优势比=5.268(1.888-14.702),P=0.002]。最常见的结外部位为头颈部、胃肠道、呼吸系统、脊柱和骨骼。高龄(>60 岁)、晚期疾病分期(III-IV 期)、治疗前乳酸脱氢酶水平升高、DLBCL 骨髓受累高东部合作肿瘤学组状态(2-4 级)和高 R-IPI 评分(3-5 级)与 R-CHOP 耐药/早期疾病复发无显著相关性(多变量分析:P>.05)。

结论及临床意义

存在一个以上结外部位的 DLBCL 患者发生 R-CHOP 耐药或 R-CHOP 治疗后早期复发的风险增加 5.268 倍。因此,有必要对存在多个结外部位疾病的 DLBCL 患者进行相关研究,以探索化疗耐药的潜在机制。

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