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

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: 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.