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Background <p>Our study aims to investigate the dynamic changes in plasma/serum EBV-DNA levels and the cytokines IL-10 and IFN-γ during early chemotherapy. This will help predict refractory EBV-HLH and guide more personalized treatment strategies.</p> Methods <p>This retrospective, single-centre cohort investigation included 117 EBV-HLH; out of these, 48 had comprehensive paired data before and after induction treatment. The median age was 3.86 years. Patients were classified based on pre-treatment plasma/serum EBV-DNA levels into high-load (≥ 5.51 × 10<sup>4</sup> copies/mL) and low-load cohorts.</p> Results <p>Patients with high plasma/serum EBV-DNA loads demonstrated a higher prevalence of DIC (20.00% vs. 3.51%, OR = 7.15) at baseline. After a two-week treatment period, the decline in EBV-DNA was strongly correlated with reductions in IFN-γ (<i>r</i> = 0.443, <i>P</i> = 0.002) and IL-10 (<i>r</i> = 0.540, <i>P</i> &lt; 0.001). Interestingly, in this study, we also found that children with a double-positive status (EBV+/IFN-γ + or EBV+/IL-10+) did not have the worst prognosis two weeks after initial treatment. However, children with HLH who are EBV (+) but cytokine (-) have a lower proportion of partial responses. Similarly, most children with HLH who are plasma or serum EBV-negative but cytokine-positive are also in the non-response period.</p> Conclusions <p>In the early stages of treatment, monitoring plasma/serum free EBV-DNA, as well as IL-10 or IFN-γ indicators, and stratifying patients is an effective method to identify children with EBV-HLH who are prone to refractory disease. This approach is of great significance for guiding their subsequent treatment.</p>

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EBV DNA load and cytokines guide risk-stratified treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Longlong Xie,
  • Xuedan Jiang,
  • Xiao Li,
  • Xun Li,
  • Xiangyu Wang,
  • Haipeng Yan,
  • Haixia Yang,
  • Ting Luo,
  • Zhenghui Xiao,
  • Meiyu Yang,
  • Xiulan Lu

摘要

Background

Our study aims to investigate the dynamic changes in plasma/serum EBV-DNA levels and the cytokines IL-10 and IFN-γ during early chemotherapy. This will help predict refractory EBV-HLH and guide more personalized treatment strategies.

Methods

This retrospective, single-centre cohort investigation included 117 EBV-HLH; out of these, 48 had comprehensive paired data before and after induction treatment. The median age was 3.86 years. Patients were classified based on pre-treatment plasma/serum EBV-DNA levels into high-load (≥ 5.51 × 104 copies/mL) and low-load cohorts.

Results

Patients with high plasma/serum EBV-DNA loads demonstrated a higher prevalence of DIC (20.00% vs. 3.51%, OR = 7.15) at baseline. After a two-week treatment period, the decline in EBV-DNA was strongly correlated with reductions in IFN-γ (r = 0.443, P = 0.002) and IL-10 (r = 0.540, P < 0.001). Interestingly, in this study, we also found that children with a double-positive status (EBV+/IFN-γ + or EBV+/IL-10+) did not have the worst prognosis two weeks after initial treatment. However, children with HLH who are EBV (+) but cytokine (-) have a lower proportion of partial responses. Similarly, most children with HLH who are plasma or serum EBV-negative but cytokine-positive are also in the non-response period.

Conclusions

In the early stages of treatment, monitoring plasma/serum free EBV-DNA, as well as IL-10 or IFN-γ indicators, and stratifying patients is an effective method to identify children with EBV-HLH who are prone to refractory disease. This approach is of great significance for guiding their subsequent treatment.