结外NK/T细胞淋巴瘤鼻型患者B症状与EBV‐DNA及细胞因子预后价值分析

目的 探讨结外NK/T细胞淋巴瘤鼻型（ENKTL）患者治疗前B症状与血浆EBV‐DNA拷贝数和血清细胞因子水平的相关关系,并分析其机制和预后价值。方法 回顾性分析资料齐全的173例患者,其中男性116例,女性57例,中位年龄43岁（4~71岁）。Ann Arbor分期Ⅰ‐Ⅱ期126例,Ⅲ‐Ⅳ期47例。肿瘤原发部位包括鼻腔（100例）、非鼻腔上呼吸消化道（34例）和上呼吸消化道以外（39例）。治疗前有和无B症状者分别为91例和82例。按照血浆EBV‐DNA拷贝数的高低分为阴性组36例、低载量（<10⁴ copies/ml）组73例和高载量（≥10⁴ copies/ml）组64例。检测的血清细胞因子包括IFN‐γ、IL‐2、IL‐4、IL‐6、IL‐10和TNF‐α。相关性分析采用Cochran‐Armitage趋势检验和Spearman相关性分析,采用Cox回归风险模型进行单因素分析评估预后影响因素并用Kaplan‐Meier法绘制生存曲线。结果 B症状及发热的发生与血浆EBV‐DNA拷贝水平的增加呈显著一致的趋势,发生B症状的患者其血清IFN‐γ、IL‐6和IL‐10的水平均高于无B症状组（P均<0.001）。血清IFN‐γ、IL‐6和IL‐10水平也均与血浆EBV‐DNA拷贝数呈正相关。B症状的发生与ENKTL患者的高危临床特征相关,包括晚期、原发肿瘤局部侵犯、区域淋巴结累及和治疗前LDH升高。单因素生存分析显示,Ann Arbor分期、B症状、血浆EBV‐DNA及上述血清细胞因子均为OS和PFS的影响因素（P均<0.05）。然而,多因素分析并未显示B症状对生存的独立预后价值。结论 ENKTL患者B症状的发生与EBV‐DNA拷贝水平和细胞因子的增高有关,这些指标也是影响ENKTL患者预后的重要因素。

Association of plasma EBV‐DNA copy number and cytokines with B symptoms in patients with extranodal natural killer/T‐cell lymphoma,nasal type

Objective To investigate the association of plasma EBV‐DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T‐cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators. Methods Clinical data of 173 newly‐diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I‐II and 47 cases of stage Ⅲ‐IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra‐upper aerodigestive tract (extra‐UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV‐DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10⁴ copies/ml, n=73) and high load group (≥10⁴ copies/ml, n=64). Serum cytokines including IFN‐γ, IL‐2, IL‐4, IL‐6, IL‐10 and TNF‐α were detected. Correlation analysis was performed by Cochran‐Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan‐Meier survival analysis. Results The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV‐DNA copy levels. In addition, serum levels of IFN‐γ, IL‐6 and IL‐10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN‐γ, IL‐6, and IL‐10 levels were also positively correlated with plasma EBV‐DNA copy number. The occurrence of B symptoms was associated with high‐risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre‐treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV‐DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression‐free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV‐DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.