EB病毒在结外NK/T细胞淋巴瘤中的预后价值：一项淮海淋巴瘤协作组的多中心回顾性研究

Prognostic value of Epstein-Barr virus in extranasal NK/T-cell lymphoma: a multi-center retrospective study from the Huaihai lymphoma cooperative group

摘要:

目的 基于倾向性评分逆处理概率加权（IPTW）法评估EB病毒（EBV）在结外NK/T细胞淋巴瘤患者中的预后价值。方法 收集2012年10月—2021年4月淮海淋巴瘤协作组中8家医疗机构初诊为结外NK/T细胞淋巴瘤且具有全血EBV-DNA数据的468例患者的临床资料。采用IPTW法分析EBV载量对结外NK/T细胞淋巴瘤患者生存期的影响；采用Cox比例风险模型进行多因素分析；绘制Kaplan-Meier曲线，组间比较采用Log rank χ²检验。结果 468例结外NK/T细胞淋巴瘤患者中，EBV-DNA阳性266例，EBV-DNA阴性202例。EBV-DNA阳性组和阴性组患者的5年OS分别为62.5%和89.2%，两组比较，经Log rank χ²检验，差异有统计学意义（χ²=42.900，P =0.000）。IPTW前，两组的美国东部肿瘤协作组（ECOG）活动状态（PS）评分（ECOG PS评分）、原发部位、CA分期、Ann Arbor分期、白蛋白、乳酸脱氢酶、治疗方案比较，差异均有统计学意义（P <0.05）。IPTW后，EBV-DNA阳性组和阴性组组间均衡，EBV-DNA阴性组患者5年OS为90.7%，而EBV-DNA阳性组患者5年OS为63.5%。Cox比例风险模型分析结果显示，EBV-DNA阳性［H^R =4.244（95% CI：2.457，7.332）］、ECOG PS ≥ 2分［H^R =2.020（95% CI：1.171，3.483）］是结外NK/T细胞淋巴瘤患者预后的不良影响因素（P < 0.05）。结论 经IPTW法平衡混杂因素后，EBV-DNA阴性患者生存情况明显优于EBV-DNA阳性患者。

Abstract:

Objective To assess the prognostic value of Epstein-Barr Virus (EBV) in patients with extranasal NK/T-cell lymphoma using inverse probability of treatment weighting (IPTW).Methods Clinical data were collected from 468 patients with extranasal NK/T-cell lymphoma diagnosed between October 2012 and April 2021 at eight medical institutions in the Huaihai Lymphoma Cooperative Group, who had complete EBV-DNA data. The impact of EBV load on the survival of extranasal NK/T-cell lymphoma patients was analyzed using IPTW. Multifactorial analysis was performed using the Cox proportional hazards model. Kaplan-Meier curves were plotted, and between-group comparisons were conducted using the log rank χ² test.Results Among the 468 patients with extranasal NK/T-cell lymphoma, 266 were EBV-DNA positive, and 202 were EBV-DNA negative. The 5-year overall survival (OS) rates for the EBV-DNA positive and negative groups were 62.5% and 89.2%, respectively, and the difference was statistically significant according to the log rank χ² test (χ² = 42.900, P = 0.000). Before IPTW, there were statistically significant differences between the EBV-DNA positive and negative groups in terms of Eastern Cooperative Oncology Group performance status (ECOG PS) score, primary site, Ann Arbor stage, albumin, lactate dehydrogenase, and treatment regimens (P < 0.05). After IPTW, the EBV-DNA positive and negative groups were balanced, and the 5-year OS for EBV-DNA negative patients was 90.7%, while the 5-year OS for EBV-DNA positive patients was 63.5%. Cox proportional hazards model analysis indicated that EBV-DNA positivity [Hazard Ratio (H^R) = 4.244 (95% CI: 2.457, 7.332) ] and ECOG PS ≥ 2 [H^R = 2.020 (95% CI: 1.171, 3.483) ] were adverse prognostic factors for extranasal NK/T-cell lymphoma patients (P < 0.05).Conclusion After balancing confounding factors through IPTW, survival outcomes for EBV-DNA negative patients were significantly better than those for EBV-DNA positive patients in extranasal NK/T-cell lymphoma.