What is the treatment for chronic Epstein-Barr virus (EBV) infection?

Treatment for Chronic Epstein-Barr Virus (EBV) Infection

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for chronic active Epstein-Barr virus (CAEBV) infection, without which patients typically die within several years. 1

Diagnosis of Chronic Active EBV Infection

Before discussing treatment, proper diagnosis is essential:

• CAEBV is diagnosed when patients have:

  • Persistent/recurrent infectious mononucleosis-like symptoms
  • Unusual patterns of anti-EBV antibodies
  • Chronic illness unexplained by other known diseases 2
  • High EBV DNA load ≥ 10,000 IU/mL in whole blood 1
  • Confirmation of EBV-infected T or NK cells 1

• Diagnostic workup should include:

  • EBV-specific antibody panel (VCA IgG, VCA IgM, EBNA)
  • Quantitative EBV PCR viral load testing 2

Treatment Approach

First-Line Management

1. For mild to moderate cases:

   • Supportive care including adequate hydration, rest, and analgesics/antipyretics 2
   • Standard antiviral drugs (acyclovir, ganciclovir) have limited efficacy against latent EBV as they primarily target lytic viral replication 2
   • Prednisolone and cyclosporine A with or without etoposide may be used for initial management 3

2. For severe cases/immunocompromised patients:

   • Rituximab therapy (375 mg/m² IV weekly until EBV DNA-emia negativity) is recommended as first-line treatment for EBV reactivation, with reported response rates of 80% 2
   • Reduction of immunosuppression if possible 2

Definitive Treatment

For confirmed CAEBV, a 3-step strategy culminating in allogeneic HSCT is recommended:

1. Disease control: Chemotherapy to control disease activity before HSCT 1
2. Preparation for HSCT: Appropriate donor selection and conditioning
3. Allogeneic HSCT: The only curative treatment option 3, 1

The 3-year overall survival rate with planned allogeneic HSCT is 87.3%, compared to only 16.7% in patients with uncontrolled active disease 3.

Second-Line Options

For patients who fail first-line therapy or as bridge to HSCT:

• Cellular therapy options:
  • EBV-specific cytotoxic T lymphocytes
  • Donor lymphocyte infusion 2
• PD-1 blockade (Sintilimab) combined with lenalidomide has shown a 54.2% overall response rate 2

Monitoring Recommendations

• Regular monitoring of EBV DNA by quantitative PCR is essential, particularly in high-risk patients 2
• Weekly EBV DNA monitoring for at least 4 months post-transplant in transplant recipients 2
• Monitor for signs of lymphoproliferative disorders, which are a significant risk in immunocompromised patients 2

Important Caveats

• Early intervention is critical: Delay in definitive treatment significantly worsens prognosis 3
• Severe hypercytokinemia and hemophagocytic syndrome may occur suddenly and result in a fatal clinical course 3
• No EBV vaccine is currently available 2
• Combination therapy with antivirals and immunomodulatory agents may be necessary as the clinical manifestations of EBV depend partly on the host immune response 4
• Antiviral therapy alone has shown minimal clinical effect in most studies 4, 5

The evidence strongly supports early diagnosis and prompt referral for HSCT evaluation in confirmed CAEBV cases, as this represents the only curative option with significantly improved survival outcomes.