血浆EB病毒DNA载量监测对单倍体造血干细胞移植后淋巴细胞增殖性疾病的预测价值

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation

目的寻找可以协助诊断单倍体造血干细胞移植(haplo-HSCT)后淋巴细胞增殖性疾病(PTLD)的EB病毒DNA(EBV-DNA)载量及其持续时间的最佳临界值。方法回顾性分析北京大学血液病研究所2016年1月至12月期间haplo-HSCT后合并EBV感染患者的相关数据,通过构建ROC曲线计算约登指数寻找对PTLD有诊断意义的EBV-DNA载量及其持续时间的临界值。结果共纳入94例患者,其中20例(21.3%)发生PTLD,诊断PTLD时中位EBV-DNA载量为70400(1710~1370000)拷贝/ml,EBV血症中位持续时间为23.5(4~490)d。二元logistic回归分析显示,PTLD组与非PTLD组两组间EBV-DNA最高载量及EBV血症持续时间差异均有统计学意义(P=0.018,P=0.001)。构建ROC曲线计算约登指数,EBV-DNA载量≥41850拷贝/ml对PTLD有诊断意义[曲线下面积(AUC)=0.847],敏感度、特异度分别为0.611、0.932;EBV血症持续时间≥20.5 d对PTLD有诊断意义(AUC=0.833),敏感度、特异度分别为0.778、0.795。结论动态监测haplo-HSCT后PTLD高危患者的EBV载量及关注其持续时间有重要临床意义,有助于预测PTLD的发生并早期采取干预措施。

Objective To determine the optimal cutoff value of Epstein-Barr virus(EBV)DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease(PTLD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed.Through constructing the receiver operating characteristic(ROC)curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD.Results A total of 94 patients were included,of whom 20(21.3%)developed PTLD,with a median onset time of 56(40-309)d after transplantation.The median EBV value at the time of diagnosis of PTLD was 70,400(1,710-1,370,000)copies/ml,and the median duration of EBV viremia was 23.5(4-490)d.Binary logistic regression was used to analyze the peak EBV-DNA load(the EBV-DNA load at the time of diagnosis in the PTLD group)and duration of EBV viremia between the PTLD and non-PTLD groups.The results showed that the difference between the two groups was statistically significant(P=0.018 and P=0.001).The ROC curve was constructed to calculate the Youden index,and it was concluded that the EBV-DNA load≥41850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD(AUC=0.847),and the sensitivity and specificity were 0.611 and 0.932,respectively.The duration of EBV viremia of≥20.5 d had diagnostic significance for PTLD(AUC=0.833),with a sensitivity and specificity of 0.778 and 0.795,respectively.Conclusion Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance,which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.