外周血淋巴细胞亚群在淋巴瘤不同EB病毒感染状态患者中的预后价值

Prognostic value of peripheral blood lymphocyte subsets in different infection status of EB virus in lymphoma patients

目的:探究外周血淋巴细胞亚群在淋巴瘤EB病毒(EBV)感染不同状态患者中的预后价值。方法:回顾性队列研究。选取2012年11月至2023年8月在徐州医科大学附属医院初诊确诊的333例淋巴瘤患者,其中弥漫性大B细胞淋巴瘤(DLBCL)组185例,NK/T细胞淋巴瘤(NKTCL)组100例,霍奇金淋巴瘤(HL)组48例。收集患者一般临床资料及实验室指标检测结果,采用流式细胞术检测淋巴细胞亚群比例、实时定量聚合酶链法检测EBV-DNA。通过查阅病例和电话随访,记录患者生存情况。采用Kaplan-Meier法绘制生存曲线,比较各组生存情况,Cox比例风险模型进行淋巴瘤生存时间相关因素分析。结果:NKTCL组中EBV-DNA阳性患者占73.0%(73/100),高于DLBCL组的43.8%(81/185)和HL组的35.4%(17/48)(P均<0.001)。Kaplan-Meier生存曲线显示,DLBCL组CD19+B细胞和CD16+CD56+NK细胞水平异常(高于或低于正常参考范围)患者、DLBCL组EBV-DNA阴性的IgA和CD19+B细胞水平异常患者、DLBCL组EBV-DNA阳性的CD16+CD56+NK细胞水平异常患者的总体生存率均低于其正常水平患者(P均<0.05)。多因素Cox回归分析结果表明,CD19+B细胞水平异常是DLBCL组患者独立不良预后的影响因素(HR=2.098,95%CI 1.181~3.727,P=0.011),EBV-DNA阳性(HR=17.623,95%CI 2.397~129.565,P=0.048)和Ann Arbor分期(Ⅲ/Ⅳ期)(HR=2.770,95%CI 1.335~5.750,P=0.006)是NKTCL患者不良预后的影响因素。结论:外周血淋巴细胞亚群在淋巴瘤不同EBV感染状态患者中存在差异,且CD19+B细胞水平可作为DLBCL患者独立预后的影响因素。

Objective To explore the prognostic value of peripheral blood lymphocyte subsets in lymphoma patients with different infection status of Epstein-Barr virus(EBV).Methods A retrospective cohort study.A total of 333 lymphoma patients newly diagnosed from November 2012 to August 2023 in the Affiliated Hospital of Xuzhou Medical University were included in the study,including 185 patients with Diffuse Large B-cell Lymphoma(DLBCL),100 patients with Natural Killer/T-cell Lymphoma(NKTCL),and 48 patients with Hodgkin Lymphoma(HL).Clinical data and laboratory indicators of patients were collected,including lymphocyte subset ratios detected by flow cytometry and EBV-DNA levels measured by real-time quantitative polymerase chain reaction.The survival status of patients was recorded through referring to medical records and telephone follow-up.The Kaplan-Meier method was used to plot survival curves and compare the survival rates among different groups.The Cox proportional hazards model was applied to analyze factors related to overall survival in lymphoma patients.Results In the NKTCL group,73.0%(73/100)were positive for EBV-DNA,which was higher than 43.8%(81/185)in the DLBCL group and 35.4%(17/48)in the HL group(P<0.001).Kaplan-Meier survival curves showed that lower overall survival rates in the DLBCL group with abnormal levels of CD19+B cells and CD16+CD56+NK cells(defined as either high or low referring to the reference intervals),with EBV-DNA negative and abnormal levels of CD19+B cells,or with EBV-DNA positive and abnormal levels of CD16+CD56+NK cells,compared with the normal level group(P<0.05).Multivariable analysis suggested that the abnormal level of CD19+B cells was an independent adverse prognostic factor for DLBCL patients(HR=2.098,95%CI 1.181-3.727,P=0.011).EBV-DNA positivity(HR=17.623,95%CI 2.397-129.565,P=0.048)and Ann Arbor stage(Ⅲ/Ⅳ)(HR=2.770,95%CI 1.335-5.750,P=0.006)were adverse prognostic factors for NKTCL patients.Conclusion There are differences in peripheral blood lymphocyte subsets among lymphoma patients with different EBV infection status,and CD19+B cell levels may serve as an independent prognostic factor for DLBCL patients.