Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hematol Oncol. 2022 Aug;40(3):381-389. doi: 10.1002/hon.2998. Epub 2022 Apr 22.
Epstein-Barr virus (EBV), characterized as an omnipresent virus, has been found able to infect NK cells and leads to NK-cell type EBV-positive lymphoproliferative diseases (EBV-NK-LPDs). We retrospective analyzed 202 EBV-NK-LPDs (including 64 CAEBV-NK, 27 aggressive natural killer-cell leukemia (ANKL), and 111 extranodal NK/T-cell lymphoma (ENKTL)) patients' relationships between EBV DNA copies laboratory test results and clinical features. In CAEBV-NK cohort, EBV DNA loads in either plasma or PBMCs had significant differences between the active state and the inactive state. Receiver operating characteristic curves were used to measure the diagnosis accuracy of EBV DNA copies. After comparing the area under the curve, EBV DNA loads in plasma had significantly higher accuracy in distinguishing disease activation than in PBMCs. Therefore, we propose redefining CAEBV-NK diagnosis criteria as increased EBV DNA copies in plasma (over 7.1 × 10 copies/ml) instead of in peripheral blood. In ANKL and ENKTL cohorts, patients who received effective therapy had significantly lower EBV DNA copies in plasma & PBMCs than in those with ineffective therapy. The significant and consistent decline indicated EBV DNA loads in plasma being a more sensitive biomarker in monitoring EBV-NK-LPDs therapy responses. Hemophagocytic lymphohistiocytosis (HLH) can occur secondary to EBV-NK-LPDs, mostly associated with a poor prognosis, so we try to estimate the combination of HLH by monitoring EBV DNA copies. When comparing the Receiver operating characteristic curves of EBV DNA copies, EBV DNA loads in plasma had higher diagnosis accuracy. When the copies level over 4.16 × 10 copies/ml, it might indicate combining with HLH.
EB 病毒（EBV）是一种普遍存在的病毒，已被发现能够感染 NK 细胞，并导致 NK 细胞型 EBV 阳性淋巴组织增生性疾病（EBV-NK-LPD）。我们回顾性分析了 202 例 EBV-NK-LPD 患者（包括 64 例 CAEBV-NK、27 例侵袭性自然杀伤细胞白血病（ANKL）和 111 例结外 NK/T 细胞淋巴瘤（ENKTL））的 EBV DNA 拷贝实验室检测结果与临床特征之间的关系。在 CAEBV-NK 组中，无论是在血浆还是 PBMC 中，EBV DNA 载量在活动期和非活动期之间均有显著差异。使用受试者工作特征曲线来衡量 EBV DNA 拷贝的诊断准确性。比较曲线下面积后，血浆中 EBV DNA 载量在区分疾病激活方面的准确性明显高于 PBMCs。因此，我们建议重新定义 CAEBV-NK 的诊断标准，即血浆中 EBV DNA 拷贝增加（超过 7.1×10 拷贝/ml），而不是外周血。在 ANKL 和 ENKTL 组中，接受有效治疗的患者的血浆和 PBMC 中 EBV DNA 载量明显低于无效治疗的患者。显著而一致的下降表明，血浆中 EBV DNA 载量在监测 EBV-NK-LPD 治疗反应方面是一种更敏感的生物标志物。EBV-NK-LPD 可继发噬血细胞性淋巴组织细胞增生症（HLH），预后大多较差，因此我们尝试通过监测 EBV DNA 拷贝来估计 HLH 的组合。比较 EBV DNA 拷贝的受试者工作特征曲线时，血浆中 EBV DNA 载量具有更高的诊断准确性。当拷贝水平超过 4.16×10 拷贝/ml 时，可能表明合并 HLH。
