What is the treatment for Epstein Barr virus infection?

Treatment of Epstein-Barr Virus Infection

For most Epstein-Barr virus (EBV) infections, supportive care is the primary treatment approach, while rituximab is the treatment of choice for severe complications such as post-transplant lymphoproliferative disorders (PTLD). 1

Management of Uncomplicated EBV Infection

• Supportive care is the mainstay of treatment for uncomplicated EBV infections, focusing on symptom relief, adequate hydration, and rest until the self-limiting infection resolves 1
• Antiviral drugs including acyclovir are ineffective against EBV and should not be used for treatment of primary EBV infection 1, 2
• Most infections are asymptomatic or self-limiting with a typical incubation period of about six weeks 3

High-Risk Populations and Monitoring

• All allogeneic hematopoietic stem cell transplant (HSCT) patients and donors should be tested for EBV antibodies before transplantation 2, 4
• Prospective monitoring of EBV DNA by quantitative PCR is recommended for high-risk patients (those receiving T-cell depleted grafts, anti-thymocyte globulin, or with GvHD) 4, 2
• Monitoring should start within the first month after allo-HSCT and continue for at least 4 months with a frequency of at least once a week 2
• In cases of persistent fever and fatigue, monitoring EBV DNA copies should be considered to exclude EBV reactivation 2

Preemptive Therapy for EBV DNA-emia

• Significant EBV DNA-emia without clinical symptoms warrants preemptive therapy with rituximab 2, 1
• Rituximab should be administered at 375 mg/m² once weekly (typically 1-4 doses) until EBV DNA-emia negativity 2, 4
• Rituximab should be combined with reduction of immunosuppression when possible 2
• Donor or third-party EBV-specific cytotoxic T lymphocytes (CTLs) should be considered if available 2, 1

Treatment of EBV-PTLD

• Rituximab (375 mg/m²) administered once weekly is the first-line treatment for EBV-PTLD, with positive outcomes in approximately 70% of patients 2, 4
• Reduction of immunosuppressive therapy should always be combined with rituximab when possible 2, 1
• Therapy should be started as soon as practicable due to the risk of rapidly growing high-grade lymphoid tumor and multi-organ impairment 2
• Additional doses of rituximab beyond 4 doses might result in down-regulation of CD20 expression and decreased efficacy 1

Special Considerations

CNS EBV Disease

• Therapeutic options for CNS EBV-PTLD include rituximab ± chemotherapy, systemic or intrathecal rituximab monotherapy, anti-EBV T-cell therapy, or radiotherapy 2, 1

Chronic Active EBV

• Hematopoietic stem cell transplantation is considered the only curative treatment for severe chronic active EBV disease 5
• Rituximab is recommended for significant EBV DNA-emia in chronic active EBV 5

Prophylaxis

• B-cell depletion with prophylactic rituximab might reduce the risk of EBV DNA-emia in high-risk patients 1, 2
• EBV-specific cytotoxic T lymphocytes (CTLs) should be considered as first-line prophylactic treatment when available 1, 2
• Antiviral drugs are not recommended for EBV prophylaxis 2, 1

Clinical Pitfalls and Caveats

• Reduction of immunosuppression alone is rarely successful for PTLD following HSCT and may increase risk of rejection or GvHD 1
• Unselected donor lymphocyte infusions can be associated with severe GvHD; previous GvHD is usually a contraindication to DLI 1
• EBV-negative B-PTLD presenting late (>5 years) after transplant should be treated as malignant lymphoma, not PTLD 1
• Severe EBV infections can rarely lead to multiorgan involvement even in immunocompetent individuals 6