Age-related Ebv-associated B-cell Lymphoproliferative Disorders Constitute a Distinct Clinicopathologic Group: a Study of 96 Patients Clinical Oncology
Age-related Ebv-associated B-cell Lymphoproliferative Disorders Constitute a Distinct Clinicopathologic Group: a Study of 96 Patients Clinical Oncology
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通讯作者：
T. Oyama;Kazuhito Yamamoto;T. Kinoshita;Shigeo Nakamura
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作者：
T. Oyama;Kazuhito Yamamoto;T. Kinoshita;Shigeo Nakamura
目的：我们最近报道了多见于老年患者的EBV+ B细胞淋巴组织增生性疾病（LPD），其特征与免疫功能恶化的患者相同，尽管没有易感性免疫缺陷，但被命名为老年或年龄相关的EBV+ B细胞LPD。将年龄相关的EBV+ B细胞LPD与EBV阴性的弥漫性大B细胞淋巴瘤（DLBCL）进行比较。实验设计：在1，792例大B细胞LPD病例中，96例具有可用临床数据集的EBV+病例入选本研究。对照组为107例年龄大于40岁的EBV阴性DLBCL患者，比较两组患者的临床病理资料，并对影响预后的因素进行单因素和多因素分析。结果如下：与年龄相关的EB病毒+B细胞LPD患者相比，EB病毒阴性DLBCL患者表现出更高的年龄分布和侵袭性临床特征或参数：44%的体力状态>1，58%的血清乳酸脱氢酶水平高于正常，49%有B症状，皮肤和肺部受累较多。因此，与年龄相关的EBV+组的总生存率显著低于DLBCL组。单变量和多变量分析进一步确定了两个因素，B症状和年龄大于70岁，独立预测生存。使用这两个变量的预后模型很好地定义了三个风险组：低风险（无不利因素），中等风险（一个因素）和高风险（两个因素）。结论：这些发现表明，年龄相关的EBV+ B细胞LPD构成了一个独特的群体，应该为这种罕见的疾病开发创新的治疗策略，如EBV靶向T细胞治疗。弥漫性大B细胞淋巴瘤（DLBCL）是最大的一类侵袭性淋巴瘤，在临床病理学特征和生物学特性方面被认为是一组异质性淋巴瘤（1）。淋巴瘤研究的最新进展阐明了DLBCL疾病分类学术语下的不同亚组，如原发性CD 5 + DLBCL（2）、血管内大B细胞淋巴瘤（亚洲变体;参考文献3）、原发性渗出性淋巴瘤（4）和脓胸相关淋巴瘤（5）。此外，我们最近发现了一系列无免疫缺陷倾向的EBV+ B细胞淋巴增生性疾病（LPD）和/或大细胞淋巴瘤老年患者，并将其命名为老年或年龄相关的EBV+ B-LPD（6）。EBV是一种普遍存在的g-疱疹病毒，感染全球90%以上的成年人群（7，8）。与其高患病率相反，EBV也被公认为明显的致癌剂（9）。它在体外将B细胞转化为淋巴母细胞系，许多人类癌症，包括伯基特淋巴瘤（BL）。
Purpose: We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs.To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL). Experimental Design: Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected.We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis. Results: Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms , and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors). Conclusions: These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease. Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphomas and regarded as a heterogeneous group of lymphomas in terms of clinicopathologic profiles and biological properties (1). Recent advance in the lymphoma research shed the light on the distinct subgroups such as de novo CD5+ DLBCL (2), intravascular large B-cell lymphoma (Asian variant; ref. 3), primary effusion lymphoma (4), and pyothorax-associated lymphoma (5) under the nosologic term of DLBCL. In addition, we have recently identified a series of elderly patients of EBV+ B-cell lymphoproliferative disorders (LPD) and/or large-cell lymphomas without predisposing immunodeficien-cies and named those senile or age-related EBV+ B-LPDs (6). EBV is a ubiquitous g-herpesvirus that infects more than 90% of worldwide adult population (7, 8). In contrast to its high prevalence, EBV is also well recognized as an apparent oncogenic agent (9). It transforms B cells into lymphoblastoid cell lines in vitro, and many human cancers, including Burkitt lymphoma (BL) …