From the Guidelines
Patients with three or more risk factors for EBV reactivation should undergo biweekly EBV monitoring, and a single dose of rituximab should be considered in those with a very high viral load, i.e., ≥1000 genome equivalents/ml. EBV reactivation is a significant concern in immunocompromised patients, particularly those with haematological malignancies and solid tumours, as it can lead to post-transplant lymphoproliferative disease (PTLD) with a poor prognosis 1. The risk factors for developing EBV-related PTLD include ex vivo T-cell depletion, treatment with antithymocyte globulin, anti-CD3 antibodies, and unrelated or HLA-mismatched transplants.
To prevent primary EBV infection, measures such as avoiding contact with potentially contaminated body fluids are recommended 1. In patients with a high risk of EBV reactivation, pre-emptive therapeutic options like rituximab, donor lymphocyte infusions (DLIs), and discontinuation of pharmacological immunosuppression can be considered, although these measures carry the risk of triggering severe graft-versus-host disease (GvHD) 1.
Key considerations for managing EBV reactivation include:
- Identifying patients with multiple risk factors for EBV reactivation and PTLD
- Implementing biweekly EBV monitoring in high-risk patients
- Using rituximab in patients with a very high viral load
- Weighing the benefits and risks of pre-emptive therapeutic options, including the potential for severe GvHD 1.
From the Research
EBV Reactivation
- EBV reactivation can occur in both immunocompromised and immunocompetent patients, with studies suggesting that it is associated with increased morbidity and mortality 2, 3.
- In immunocompromised patients, EBV reactivation has been linked to various malignancies, including nasopharyngeal carcinoma, gastric carcinoma, and lymphomas such as Burkitt Lymphoma and Post-transplant Lymphoproliferative Disorder 4.
- Reactivation of EBV in critically ill immunocompetent patients has been observed, with one study detecting EBV DNA in the blood of 61 out of 90 patients, and finding an association between EBV reactivation and increased length of stay and mechanical ventilation 2.
- Treatment of EBV reactivation often involves antiviral medications such as ganciclovir and foscarnet, with some studies suggesting that combination therapy with methotrexate may be effective in certain cases 5, 6.
- A prospective observational study found that EBV reactivation was associated with increased morbidity, including fewer ventilator-free days, a higher incidence of acute respiratory distress syndrome, and a greater need for renal replacement therapy 3.
Risk Factors and Associations
- EBV reactivation has been associated with increased mortality in some studies, although one study found no difference in 90-day mortality rates between patients with and without reactivation 2, 3.
- The presence of EBV reactivation at ICU admission has been linked to increased mortality compared to those without reactivation or with later reactivation 3.
- EBV reactivation has also been associated with a more inflammatory immune profile, which may contribute to the increased morbidity observed in these patients 3.
Treatment and Management
- Antiviral medications such as ganciclovir and foscarnet are commonly used to treat EBV reactivation, with some studies suggesting that combination therapy with methotrexate may be effective in certain cases 5, 6.
- Further research is needed to determine the optimal treatment strategy for EBV reactivation, particularly in immunocompromised patients 4.