Clinical utility of plasma Epstein-Barr virus DNA monitoring in pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: a Chinese retrospective observational study

Ital J Pediatr. 2024 Jul 30;50(1):139. doi: 10.1186/s13052-024-01689-8.

Abstract

Background: Epstein-Barr virus DNA (EBV-DNA) is closely related to the pathogenesis and prognosis of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The quantitative measurement of blood EBV-DNA is widely used in EBV-HLH, but there remains a lack of evidence to guide clinicians.

Methods: A retrospective analysis was conducted on clinical manifestations, laboratory tests, 310 blood EBV-DNA loads, and prognosis of 51 pediatric patients diagnosed with EBV-HLH. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff values of EBV-DNA for predicting mortality and evaluating the active status of EBV-HLH.

Results: EBV-positive- lymphoma-HLH had higher initial plasma EBV-DNA load(1.10 × 106copies/ml) compared to the EBV-HLH group (1.98 × 104 copies/ml) (P = 0.006), and experienced recurrently elevated plasma EBV-DNA levels during treatment. The optimal cut-off value of initial plasma EBV-DNA load in predicting mortality was 2.68 × 105 copies/ml, with a sensitivity of 88.57% and a specificity of 56.25%. For determining the active status of HLH, the optimal cutoff value of PBMC EBV-DNA load during treatment was 2.95 × 105 copies/ml, with a sensitivity of 69.14% and a specificity of 64.71%. The cut-off value of plasma EBV-DNA for determining active status was 1.32 × 103 copies/ml, with a sensitivity of 84.34%, and a specificity of 87.67%. Patients with higher PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses (P < 0.05).

Conclusion: Dynamic monitoring of EBV-DNA is a valuable tool for assessing disease status and predicting the prognosis of EBV-HLH, with plasma EBV-DNA being more effective than PBMC EBV-DNA. Patients with high levels of PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses.

Keywords: Epstein-Barr virus DNA; Hemophagocytic lymphohistiocytosis; Pediatric; Prognosis.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • China
  • DNA, Viral* / blood
  • East Asian People
  • Epstein-Barr Virus Infections* / blood
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / diagnosis
  • Female
  • Herpesvirus 4, Human* / genetics
  • Humans
  • Infant
  • Lymphohistiocytosis, Hemophagocytic* / blood
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / virology
  • Male
  • Prognosis
  • Retrospective Studies
  • Viral Load

Substances

  • DNA, Viral