Treatment of Epstein-Barr Virus (EBV) Infections
Primary Treatment Approach
For most EBV infections in immunocompetent patients, supportive care is the only treatment needed, as the infection is self-limiting and antiviral drugs like acyclovir are completely ineffective against EBV. 1, 2
Supportive Care for Uncomplicated EBV
- Focus on symptom relief, adequate hydration, and rest until the infection resolves spontaneously 1
- Corticosteroids may be considered for severe complications (airway obstruction, severe thrombocytopenia, hemolytic anemia), but this is not routine treatment 3
- Do not prescribe acyclovir, valacyclovir, or other antivirals—they have no efficacy against latent or active EBV 1, 2
High-Risk Populations Requiring Active Intervention
Post-Transplant Patients (Allogeneic HSCT)
All allogeneic HSCT patients require prospective EBV DNA monitoring by quantitative PCR for at least 4 months post-transplant 1, 2
Prophylaxis Strategy:
- EBV-specific cytotoxic T lymphocytes (CTLs) should be considered as first-line prophylaxis when available 1, 2
- B-cell depletion with prophylactic rituximab may reduce EBV DNA-emia risk 1
- Test all donors and recipients for EBV antibodies before transplantation 1
Preemptive Therapy for EBV DNA-emia:
- When significant EBV DNA-emia develops without clinical symptoms, initiate rituximab 375 mg/m² once weekly for 1-4 doses until EBV DNA negativity 1, 2, 4
Treatment of EBV Post-Transplant Lymphoproliferative Disorder (PTLD)
Rituximab 375 mg/m² once weekly is the first-line treatment for EBV-PTLD, achieving positive outcomes in approximately 70% of patients 5, 1, 2
First-Line Therapy Algorithm:
- Rituximab 375 mg/m² weekly for 1-4 doses 5, 1, 2
- Reduce immunosuppression when possible (combine with rituximab) 5, 1, 2, 4
- Consider EBV-specific CTLs if available 5, 1
Second-Line Options (if first-line fails):
- Unselected donor lymphocyte infusions (DLI)—but only if no prior graft-versus-host disease (GvHD), as DLI carries severe GvHD risk 1
- Chemotherapy protocols 5
CNS EBV-PTLD Specific Approach:
- Rituximab ± chemotherapy based on primary CNS lymphoma protocols 1
- Systemic or intrathecal rituximab monotherapy 1
- EBV-specific CTLs 1
- Radiotherapy as an option 1
Chronic Active EBV (CAEBV)
Hematopoietic stem cell transplantation is the only curative treatment for severe CAEBV and should be pursued when available 4
- Diagnosis requires persistent symptoms (fever, lymphadenopathy, hepatosplenomegaly) for >3 months with elevated EBV antibody titers (VCA-IgG ≥1:640, EA-IgG ≥1:160) 4
- Rituximab 375 mg/m² weekly for significant EBV DNA-emia 4
- Reduce immunosuppression when applicable 4
Critical Pitfalls to Avoid
What NOT to Do:
- Never prescribe antiviral drugs (acyclovir, ganciclovir, foscarnet) for EBV—they are ineffective against latent EBV and do not improve outcomes 1, 2. While some case reports suggest benefit when combined with steroids for severe complications 3, 6, current guidelines from the European Society for Blood and Marrow Transplantation explicitly discourage their use 5, 1
- Do not rely on reduction of immunosuppression alone for PTLD after HSCT—it is rarely successful and increases GvHD/rejection risk 1, 2
- Do not give more than 4 doses of rituximab initially—additional doses may cause CD20 down-regulation and decreased efficacy 1
- Do not use unselected DLI if patient has history of GvHD—this is usually a contraindication 1
Special Populations:
- EBV-negative B-PTLD presenting >5 years post-transplant should be treated as malignant lymphoma with chemotherapy, not as PTLD 1
- Patients on thiopurines have increased risk of EBV-associated lymphoproliferative disorders 4
Past EBV Infection (Asymptomatic)
No treatment or monitoring is needed for immunocompetent individuals with past EBV infection (VCA IgG+, EBNA IgG+, VCA IgM-) 2