Prognostic significance of plasma and whole blood Epstein-Barr virus-DNA load during treatment in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis / 中华实用儿科临床杂志

ABSTRACT

Objective:To evaluate the prognostic value of Epstein-Barr virus (EBV)-DNA level in plasma and whole blood in treatment of children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:Clinical data of 66 children with EBV-HLH, who were admitted to the Hematology and Oncology Center of Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2017 were retrospectively reviewed and analyzed.The data included the dynamic changes of the EBV-DNA level in plasma (P-EBV-DNA) and whole blood (W-EBV-DNA) at the time of admission, 2 and 4 weeks after treatment.P-EBV-DNA was divided into the positive group and the negative group according to the copy number of EBV-DNA, and W-EBV-DNA was divided into the high and the low level group by the receiver operating characteristic curve(ROC); the incidence of poor prognosis was compared between different groups by Chi- Square test; the event-free survival (EFS)was evaluated by the Log- Rank test to identify its prognostic significance. Results:The analysis showed that both P-EBV-DNA and W-EBV-DNA at admission could not be associated with a poor outcome; P-EBV-DNA (≥500 copies/mL) or W-EBV-DNA [>(5.04-5.09)×10 5 copies/mL]after 2 and 4 weeks of treatment could be a good marker of a poor outcome and progression-free survival ( P<0.001). Besides, central nervous system (CNS) involvement ( P=0.025), sever leukopenia(WBC≤3×10 9/L, P=0.031), neutropenia (ANC ≤0.5×10 9/L, P=0.041), albumin reduction (≤26 g/L, P=0.012) and hemoglobin decrease (≤90 g/L, P=0.023) at diagnosis are also associa-ted with worse outcomes.In multivariate analysis, only P-EBV-DNA at 4 th week and CNS involvement were indepen-dent prognostic factors ( HR=7.139, P=0.032 and HR=6.455, P=0.042, respectively). The prognostic value of W-EBV-DNA at different time points and P-EBV-DNA after 2 weeks of treatment had a lower prognostic value. Conclusions:The P-EBV-DNA level after 4 weeks of treatment is a promising risk indicator for early diagnosis of disease and early recognition of poor prognosis in EBV-HLH children, so it provides the guidance for optimal treatment.