文章：

具有长期随访的原发性纵隔大B细胞淋巴瘤患者的预后因素、治疗方法和独特的免疫生物学特征

Prognostic factors, therapeutic approaches, and distinct immunobiologic features in patients with primary mediastinal large B-cell lymphoma on long-term follow-up

原文发布日期：2020-05-04

DOI: 10.1038/s41408-020-0312-7

类型: Article

开放获取: 是

英文摘要：

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare and distinct subtype of diffuse large B-cell lymphoma (DLBCL) without prognostic factors or a single standard of treatment clearly defined. In this study we performed retrospective analysis for clinical outcomes of 166 patients with PMBCL. In overall PMBCL, higher International Prognostic Index, stage, Ki-67 proliferation index, and positron emission tomography (PET) maximum standardized uptake values (SUVmax) at diagnosis were significantly associated with poorer survival, whereas MUM1 expression and higher peripheral blood lymphocyte/monocyte ratios were significantly associated with better survival. Patients who received R-HCVAD or R-EPOCH had better clinical outcome than did those who received the standard treatment R-CHOP. Treatment response and end-of-treatment PET SUVmax had remarkable correlations with survival outcome. In patients with refractory or relapsed PMBCL, stem cell transplant significantly improved overall survival. PMBCL had distinct gene expression signatures compared with overall DLBCL–NOS but not with DLBCL with PD-L1/PD-L2 amplification. PMBCL also showed higher PD-L2 expression in B-cells, lower PD-1 expression in T-cells, and higher CTLA-4 expression in T-cells and distinct miRNA signatures compared with DLBCL-NOS. The prognostic factors, effectiveness of treatment, transcriptional and epigenetic signatures, and immunologic features revealed by this study enrich our understanding of PMBCL biology and support future treatment strategy.
 

摘要翻译： 

原发性纵隔大B细胞淋巴瘤（PMBCL）是一种罕见且独特的弥漫性大B细胞淋巴瘤（DLBCL）亚型，其预后因素和单一治疗标准尚未明确。本研究对166例PMBCL患者进行了临床结局的回顾性分析。在整体PMBCL患者中，较高的国际预后指数、分期、Ki-67增殖指数以及诊断时正电子发射断层扫描（PET）最大标准化摄取值（SUVmax）与较差的生存率显著相关，而MUM1表达和较高的外周血淋巴细胞/单核细胞比值则与较好的生存率显著相关。接受R-HCVAD或R-EPOCH方案治疗的患者比接受标准R-CHOP方案治疗的患者临床结局更好。治疗反应和治疗结束时PET SUVmax与生存结局显著相关。在难治性或复发性PMBCL患者中，干细胞移植显著提高了总生存率。与整体非特指型DLBCL（DLBCL-NOS）相比，PMBCL具有独特的基因表达特征，但与PD-L1/PD-L2扩增的DLBCL无差异。相较于DLBCL-NOS，PMBCL还表现出B细胞中PD-L2表达更高、T细胞中PD-1表达更低、T细胞中CTLA-4表达更高以及独特的miRNA特征谱。本研究揭示的预后因素、治疗有效性、转录组和表观遗传特征以及免疫学特征，丰富了我们对PMBCL生物学的理解，并为未来治疗策略提供了支持。

原文链接：

Prognostic factors, therapeutic approaches, and distinct immunobiologic features in patients with primary mediastinal large B-cell lymphoma on long-term follow-up