Department of Haematology and Oncology, Federal Armed Hospital Ulm, Ulm, Germany.
Department of Haematology and Oncology, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Br J Haematol. 2020 Apr;189(2):257-268. doi: 10.1111/bjh.16342. Epub 2020 Jan 20.
Patients with EBV-positive diffuse large B cell lymphoma not otherwise specified (EBV DLBCL (NOS)) recurrently present with advanced age and reduced performance status. They are therefore insufficiently represented in clinical trials and treatment is likely to differ. Here we assess clinicopathological characteristics, therapeutic variability and clinical outcome in the largest consecutively diagnosed EBV DLBCL (NOS) cohort published to date (n = 80; median age 70 years; range 19-90). Centralized and systematic haematopathological panel review was performed. By immunohistochemistry 60/80 patients were CD30-positive. Further, we identified nine EBV DLBCL (NOS) patients with associated or composite peripheral T cell lymphoma at diagnosis or relapse (preceded by clonal T cell populations within the initial DLBCL biopsy in 4/5 cases). Most patients (80%) were treated with R-CHOP-type therapy and 16 patients received none or less intensiveprotocols. Upon univariate analysis both R-CHOP-type therapy (OS: P < 0.0001; PFS: P = 0.0617) and negativity for CD30 (OS: P = 0.0002; PFS: P = 0.0002) showed a protective 66 effect, maintained upon multivariate analysis. In a propensity-score matched analysis with a cohort of non-EBV DLBCL (NOS) patients, balanced for all revised-international prognostic index factors, we found an EBV-association to hold no significant impact on progression-free and overall survival whilst exhibiting a trend favouring EBV-negativity (OS: P = 0.116; PFS: P = 0.269). Our findings provide insight into the clinical course of EBV DLBCL (NOS), highlight the ramifications of CD30-expression and underline the superior therapeutic efficacy of R-CHOP immunochemotherapy. Alternative therapies, incorporating tumour biology (e.g. CD30 directed therapies) need to be explored in EBV DLBCL (NOS) patients. Moreover our data advert to the close relationship between EBV DLBCL (NOS) and peripheral T cell lymphomas.
患者患有 EBV 阳性弥漫性大 B 细胞淋巴瘤非特指型（EBV DLBCL（NOS）），通常具有高龄和较差的体能状态等特征。因此，他们在临床试验中的代表性不足，治疗方法可能也有所不同。在此，我们评估了迄今为止发表的最大的 EBV DLBCL（NOS）连续诊断队列的临床病理特征、治疗变异性和临床结局（n=80；中位年龄 70 岁；范围 19-90 岁）。进行了集中和系统的血液病理学小组审查。通过免疫组化，60/80 例患者 CD30 阳性。此外，我们在诊断或复发时发现了 9 例与 EBV DLBCL（NOS）相关或复合外周 T 细胞淋巴瘤的患者（在 4/5 例病例中，最初的 DLBCL 活检中存在克隆性 T 细胞群）。大多数患者（80%）接受了 R-CHOP 类治疗，16 名患者接受了非强化或低强度治疗方案。单因素分析显示，R-CHOP 类治疗（OS：P<0.0001；PFS：P=0.0617）和 CD30 阴性（OS：P=0.0002；PFS：P=0.0002）均具有保护性作用，多因素分析结果保持不变。在与非 EBV DLBCL（NOS）患者的队列进行倾向评分匹配分析中，对所有修正的国际预后指数因素进行了平衡，我们发现 EBV 相关性对无进展生存期和总生存期没有显著影响，而 EBV 阴性具有趋势（OS：P=0.116；PFS：P=0.269）。我们的研究结果提供了 EBV DLBCL（NOS）的临床过程的深入了解，强调了 CD30 表达的影响，并强调了 R-CHOP 免疫化疗的卓越疗效。需要探索包括肿瘤生物学在内的替代疗法（例如，针对 CD30 的疗法），以应用于 EBV DLBCL（NOS）患者。此外，我们的数据表明 EBV DLBCL（NOS）与外周 T 细胞淋巴瘤之间存在密切关系。
