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

Treatment of Epstein-Barr Virus (EBV)

For most EBV infections, supportive care is the primary treatment, while specific interventions like rituximab are reserved for severe complications such as post-transplant lymphoproliferative disorders (PTLD). 1

General Management of Uncomplicated EBV Infection

• Uncomplicated EBV infections (infectious mononucleosis) typically require only supportive care, as antiviral drugs have not shown significant clinical benefit 2
• Management focuses on symptom relief, adequate hydration, and rest until the self-limiting infection resolves 1
• Antiviral drugs like acyclovir have demonstrated minimal effects on clinical symptoms despite inhibiting oropharyngeal EBV replication 2

Management of EBV in High-Risk Populations

• All allogeneic hematopoietic stem cell transplant (HSCT) patients and donors should be tested for EBV antibodies before transplantation 1
• High-risk patients (those receiving T-cell depleted grafts, anti-thymocyte globulin, or with GvHD) require prospective monitoring of EBV DNA-emia by quantitative PCR 1
• Prophylactic options:
  • B-cell depletion with prophylactic rituximab might reduce the risk of EBV DNA-emia 3
  • EBV-specific cytotoxic T lymphocytes (CTLs) should be considered as first-line prophylactic treatment when available 3
  • Antiviral drugs, interferon, and IVIG are not recommended for EBV prophylaxis 3

Preemptive Therapy for EBV DNA-emia

• Significant EBV DNA-emia without clinical symptoms warrants preemptive therapy with rituximab 3
• Recommended regimen:
  • Rituximab 375 mg/m² once weekly (1-4 doses) until EBV DNA-emia negativity 3, 1
  • Reduction of immunosuppression should be combined with rituximab when possible 3
  • EBV-specific CTLs should be considered if available 3
• Antiviral drugs are not recommended for preemptive therapy 3

Treatment of EBV-PTLD

First-line therapy

• Rituximab (375 mg/m²) administered once weekly is the treatment of choice for EBV-PTLD, with positive outcomes in approximately 70% of patients 3, 1
• Reduction of immunosuppressive therapy should always be combined with rituximab when possible 3
• Cellular therapy with donor or third-party EBV-specific CTLs should be considered if available 3
• Treatment should be initiated promptly due to risk of rapidly growing high-grade lymphoid tumors 3
• Response to rituximab therapy can be identified by a decrease in EBV DNA-emia of at least 1 log10 in the first week of treatment 3

Second-line therapy

• Cellular therapy (EBV-specific CTLs or donor lymphocyte infusion) is preferred when rituximab fails 3
• Chemotherapy ± rituximab is a potential option after failure of other methods 3
• Surgery, IVIG, interferon, and antiviral agents are not recommended for PTLD therapy 3

Management of Chronic Active EBV Infection (CAEBV)

• CAEBV is characterized by systemic inflammation and clonal proliferation of EBV-infected T or NK cells 4
• Diagnosis requires confirmation of high EBV DNA load (≥10,000 IU/mL in whole blood) and EBV-infected T or NK cells 4
• Treatment approach:
  • Hematopoietic stem cell transplantation (HSCT) is the only curative treatment 5, 4
  • Chemotherapy may be administered to control disease activity before HSCT 4
  • Without HSCT, patients with CAEBV typically die within several years 5

Special Considerations for CNS EBV Disease

• CNS localization of EBV-PTLD requires special consideration due to risk of neurocognitive dysfunction 3
• Therapeutic options include:
  • Rituximab ± chemotherapy based on primary CNS lymphoma protocols 3
  • Systemic or intrathecal rituximab monotherapy 3
  • T-cell therapy with EBV-specific CTLs 3
  • Radiotherapy 3

Clinical Pitfalls and Caveats

• Antiviral drugs (including acyclovir) are ineffective against EBV and should not be used for treatment 3, 6
• Reduction of immunosuppression alone is rarely successful for PTLD following HSCT and may increase risk of rejection or GvHD 3
• Additional doses of rituximab beyond 4 doses might result in down-regulation of CD20 expression and decreased efficacy 3
• Unselected donor lymphocyte infusions can be associated with severe GvHD; previous GvHD is usually a contraindication to DLI 3
• EBV-negative B-PTLD presenting late (>5 years) after transplant should be regarded as malignant lymphoma, not PTLD, and treated with appropriate chemotherapy protocols 3