Preemptive Rituximab for Epstein-Barr Virus Reactivation After Hematopoietic Cell Transplantation: Necessary for All?

In allogeneic HCT recipients, risk factors for PTLD and EBV end-organ diseases are well established. Therefore, weekly monitoring of EBV reactivation with quantitative PCR is indicated for patients at risk. Although based on uncontrolled studies and supported by moderate strength of evidence, preemptive rituximab has been recommended in cases of EBV reactivation, without a clearly defined EBV DNAemia threshold. Rituximab is known to be associated with prolonged B-cell depletion and secondary hypogammaglobulinemia, resulting in an increased risk of infectious complications and poor vaccine responses for an extended period.

In this retrospective single-center study, we evaluated the safety and effectiveness of immunosuppression (IS) reduction as the first approach in EBV reactivation in 328 HCT recipients, limiting the introduction of rituximab to patients who did not respond to IS reduction or who developed EBV end-organ disease or PTLD.

During follow-up, 178 patients experienced EBV reactivation, with a cumulative incidence of 54.6%. Among these, four patients developed EBV encephalitis (2.2%), and no cases of PTLD were identified. Rituximab was administered to only 12 patients (6.7%). In multivariate analysis, EBV reactivation was significantly associated with chronic GVHD, which may be related to EBV reactivation itself, rapid IS withdrawal, or both. EBV reactivation did not adversely affect non-relapse mortality or overall survival in this cohort.

IS reduction as the first-line approach to EBV reactivation was safe and effective in most patients with increasing EBV DNAemia. Consequently, rituximab was required in fewer than 10% of cases.