What is the treatment for exacerbation of Epstein-Barr Virus (EBV)?

Treatment for Epstein-Barr Virus (EBV) Exacerbation

Rituximab therapy at a dose of 375 mg/m² intravenously once weekly until EBV DNA-emia negativity is the recommended first-line treatment for EBV reactivation, with reduction of immunosuppression if possible. 1

Diagnosis Confirmation

Before initiating treatment, it's essential to confirm EBV reactivation through:

• Quantitative EBV PCR viral load testing
• EBV-specific antibody panel (VCA-IgG ≥1:640 and EA-IgG ≥1:160 typically indicate active infection)
• Consider EBER in situ hybridization for suspected lymphoproliferative disorders 1

Treatment Algorithm

First-line Treatment:

1. Rituximab therapy
   • Dosage: 375 mg/m² intravenously once weekly
   • Continue until EBV DNA-emia negativity
   • Response rate: approximately 80% 1
   • Reduce immunosuppression if applicable

Second-line Options:

1. Cellular therapy

   • EBV-specific cytotoxic T lymphocytes (EBV-CTL)
   • Donor lymphocyte infusion
   • Autologous EBV-CTL therapy (shown success with 4 of 5 patients remaining relapse-free) 1

2. Combination therapy

   • PD-1 blockade (Sintilimab) with lenalidomide
   • Overall response rate: 54.2%
   • Complete response: 45.8% of patients 1

For Persistent Fatigue Cases:

• Consider valacyclovir at 1.0-1.5 g every 6 hours, although evidence is limited 1

Special Considerations

Chronic Active EBV (CAEBV)

CAEBV is diagnosed when all three criteria are met:

• Persistent/recurrent infectious mononucleosis-like symptoms
• Unusual pattern of anti-EBV antibodies with raised anti-VCA and anti-EA
• Chronic illness unexplained by other known diseases 1

For CAEBV, the American Society of Hematology recommends:

• First-line immunomodulative therapy with prednisolone and cyclosporine A with or without etoposide
• Goal: Control disease activity before proceeding to transplantation
• 3-year overall survival rate: 87.3% when disease is controlled before transplant 1

High-Risk Patients (Transplant Recipients/Immunocompromised)

• Consider prophylactic or preemptive rituximab 1
• Weekly EBV DNA monitoring by quantitative PCR
  • Start within first month after transplant
  • Continue for at least 4 months post-transplant
  • Reduces PTLD incidence by 50% 1

Monitoring Protocol

• Regular follow-up every 4-8 weeks
• Monitor:
  • Symptoms
  • Laboratory findings (EBV viral load)
  • Complications
• Use unfractionated whole blood for EBV DNA monitoring 1
• Watch for signs of lymphoproliferative disorders:
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Worsening cytopenias
  • Hypercytokinemia and hemophagocytic syndrome (can be fatal) 1

Important Caveats

• Standard antiviral drugs (acyclovir, ganciclovir) have limited efficacy against latent EBV 1, 2
• Earlier initiation of allogeneic HSCT is recommended for better outcomes in severe cases, with survival dropping dramatically to 16.7% in patients with uncontrolled active disease 1
• Corticosteroids may have a role in specific complications but should be used judiciously 3
• The clinical presentation of chronic active EBV infection can be heterogeneous, requiring flexible application of diagnostic criteria 4

Emerging Therapies

• Adoptive transfer of virus-specific cytotoxic T lymphocytes
• Gene therapy approaches targeting specific EBV genes
• Reported response rate: 50% 1