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在利妥昔单抗时代,乙型肝炎表面抗原阳性是弥漫性大 B 细胞淋巴瘤的独立不良预后因素。

Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor in Diffuse Large B-Cell Lymphoma in the Rituximab Era.

机构信息

Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan.

Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.

出版信息

Oncologist. 2020 Sep;25(9):793-802. doi: 10.1634/theoncologist.2019-0756. Epub 2020 Apr 27.

Abstract

BACKGROUND

Patients with diffuse large B-cell lymphoma (DLBCL) with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear.

MATERIALS AND METHODS

We conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016.

RESULTS

Among 416 analyzed patients, 98 (23.6%) were HBsAg positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, p = .043), poorer 5-year overall survival (OS) rate (57.2% vs. 73.5%, p < .001), and shorter 5-year progression-free survival (PFS) rate (47.2% vs. 60.7%, p = .013). Multivariate analyses showed that HBsAg positivity was an independent unfavorable prognostic indicator for OS and PFS. A scoring system incorporating HBsAg positivity, the NCCN-IPI score, and serum albumin levels proved to be useful for stratifying prognostically relevant subgroups of patients with DLBCL.

CONCLUSION

This study demonstrated that HBV infection is uniquely relevant to DLBCL. HBsAg might serve as a novel biomarker to improve clinical risk stratification of patients with DLBCL in areas with high prevalence of HBV infection. Further research investigating the etiopathogenesis of HBV infection in DLBCL is imperative.

IMPLICATIONS FOR PRACTICE

A considerable disparity exists regarding the prognostic relevance of hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection in patients with diffuse large B-cell lymphoma (DLBCL). In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era.

摘要

背景

患有合并乙型肝炎表面抗原(HBsAg)阳性乙型肝炎病毒(HBV)感染的弥漫性大 B 细胞淋巴瘤(DLBCL)患者具有独特的临床特征。然而,在利妥昔单抗时代,HBsAg 在 DLBCL 中的预后价值尚不清楚。

材料与方法

我们进行了一项回顾性队列研究,调查了 2002 年至 2016 年间,接受同种异体利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松治疗的免疫功能正常的 DLBCL 患者中 HBsAg 的临床相关性。

结果

在分析的 416 例患者中,98 例(23.6%)为 HBsAg 阳性。HBsAg 阳性与年龄较小、诊断时分期较晚、化疗期间肝损伤更频繁以及诊断时国家综合癌症网络-国际预后指数(NCCN-IPI)评分更高有关。与 HBsAg 阴性患者相比,HBsAg 阳性患者的总体缓解率较低(76.5% vs. 85.5%,p =.043),5 年总生存率较低(57.2% vs. 73.5%,p <.001),5 年无进展生存率较低(47.2% vs. 60.7%,p =.013)。多变量分析表明,HBsAg 阳性是 OS 和 PFS 的独立不良预后因素。包含 HBsAg 阳性、NCCN-IPI 评分和血清白蛋白水平的评分系统证明可用于分层 DLBCL 患者具有预后意义的亚组。

结论

本研究表明 HBV 感染与 DLBCL 有独特的相关性。HBsAg 可能作为一种新的生物标志物,用于改善 HBV 感染高发地区 DLBCL 患者的临床风险分层。进一步研究 HBV 感染在 DLBCL 中的病因发病机制至关重要。

意义

对于乙型肝炎表面抗原(HBsAg)阳性乙型肝炎病毒(HBV)感染对弥漫性大 B 细胞淋巴瘤(DLBCL)患者的预后相关性,存在相当大的差异。在这项来自 HBV 感染高发地区的大型回顾性队列研究中,作者证明 HBsAg 是一个独立的不利因素,与生存显著相关,突出了其作为一种新的预后指标的潜力,可在利妥昔单抗时代改善 DLBCL 患者的风险分层。

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