Supplementary Material for: Clinical Significance of Plasma Epstein-Barr Virus DNA in Peripheral T-Cell Lymphomas

Introduction: The clinical implications of plasma Epstein-Barr virus (EBV) DNA in patients with peripheral T-cell lymphoma (PTCL) remain unclear. Objective: This study aimed to explore the clinical correlations of pre- and post-treatment plasma EBV-DNA concentrations with treatment outcomes and prognosis in patients with PTCL. Methods: We retrospectively reviewed 128 patients diagnosed with PTCL with available data on pre-treatment plasma EBV-DNA, including 63 patients for whom post-treatment plasma EBV-DNA data were also available. Patients with extra-nodal NK/T-cell lymphoma were excluded from this study. Results: Pre-treatment plasma EBV-DNA was elevated (e.g., ≥500 copies/mL) in 35.2% of PTCL patients, with significant differences in positive rates between different subtypes of PTCL (p 60 years), elevated lactate dehydrogenase levels, high International Prognostic Index (IPI), and positive EBV-encoded RNAs-ISH in tumor specimens. In multivariate analyses, pre-treatment EBV-DNA ≥500 copies/mL was an independent prognostic factor after adjusting for IPI and pathological subtypes (hazard ratio = 2.14, p = 0.032). For patients with elevated pre-treatment EBV-DNA, normalization of EBV-DNA concentrations after first-line chemotherapy was significantly associated with better overall response rate (81.3% vs. 22.2%, p = 0.014), progression-free survival (12.0 months vs. 3.7 months, p = 0.011), and overall survival (37.9 months vs. 7.8 months, p = 0.012). For patients achieving remission to first-line therapy, rebound of EBV-DNA levels during follow-up was associated with disease relapse or progression. Conclusions: These results suggest that pre-treatment plasma EBV-DNA concentration is a strong prognostic factor for PTCL. For patients with elevated pre-treatment EBV-DNA, dynamic monitoring of EBV-DNA changes after initiation of therapy is useful for predicting treatment outcome and disease relapse.背景：外周T细胞淋巴瘤（peripheral T-cell lymphoma, PTCL）患者血浆EB病毒（Epstein-Barr virus, EBV）DNA的临床意义至今仍不明确。 目的：本研究旨在探讨外周T细胞淋巴瘤患者治疗前后血浆EB病毒DNA（EBV-DNA）浓度与治疗结局及预后的临床相关性。 方法：本研究回顾性分析了128例确诊为PTCL且具备治疗前血浆EBV-DNA检测数据的患者，其中63例同时拥有治疗后血浆EBV-DNA检测数据。本研究排除了结外NK/T细胞淋巴瘤患者。 结果：35.2%的PTCL患者治疗前血浆EBV-DNA水平升高（例如≥500 copies/mL），不同PTCL亚型间的阳性率存在显著差异（p < 0.05）。治疗前EBV-DNA升高与临床分期偏晚、年龄≥60岁、乳酸脱氢酶水平升高、高国际预后指数（International Prognostic Index, IPI）以及肿瘤标本中EB病毒编码RNA原位杂交（EBV-encoded RNAs-ISH）阳性显著相关。多因素分析显示，在校正IPI及病理亚型后，治疗前EBV-DNA≥500 copies/mL是独立的预后因素（风险比=2.14，p=0.032）。对于治疗前EBV-DNA升高的患者，一线化疗后EBV-DNA浓度恢复正常者，其总缓解率（81.3% vs. 22.2%，p=0.014）、无进展生存期（12.0个月 vs. 3.7个月，p=0.011）及总生存期（37.9个月 vs. 7.8个月，p=0.012）均显著更优。对于一线治疗后达到缓解的患者，随访期间EBV-DNA水平反弹与疾病复发或进展相关。 结论：本研究结果表明，治疗前血浆EBV-DNA浓度是PTCL的强预后因素。对于治疗前EBV-DNA升高的患者，治疗启动后动态监测EBV-DNA变化有助于预测治疗结局及疾病复发。