Background: Epstein-Barr virus (EBV) infection is a known risk factor for the development of post-transplant lymphoproliferative disease (PTLD), which occurs as a consequence of immunosuppression after kidney transplantation. Although reduction of immunosuppression and initiation of antiviral therapy is recommended in clinical practice, there are no guidelines for the preemptive use of rituximab to reduce the risk of PTLD in patients with refractory EBV viremia. The aim of our study was to evaluate the clinical efficacy and safety profile of rituximab treatment in pediatric kidney transplant patients with refractory EBV viremia.
Methods: We evaluated 112 pediatric patients who underwent kidney transplantation at median age 8.3 years (IQR 4-13.3) in Koç University Hospital between June 2018 and December 2023. Treatment for EBV viremia was initiated at a threshold of greater than 300 copies/mL by starting Valganciclovir simultaneously with reduction of immunosuppression. Patients with refractory EBV viremia at the end of the 3rd month of standard treatment initiation were treated with rituximab (Rituximab 375mg/m2). We compared outcomes of EBV clearance, graft function, allograft and patient survival for patients who did not receive rituksimab and those who received rituksimab. Additionaly the side effects of the rituksimab were evaluated.
Results: Of 112 patients who underwent kidney transplantation and were followed for a median of 30 months (IQR 17-47.25), 28 (25%) developed EBV viremia at a median of 269 days post-transplant (IQR: 36-4102).  At the time of transplantation, 18/28 (64.3%) of these patients were seronegative and 10/28 (35.7%) were seropositive for EBV. After the initiation of standard treatment, 10 of the 28 (35.7 %) respond to this strategy and cleared EBV while 18 of the 28 (64.3 %)  patients continued to  have EBV viremia  defined as 500 copies/mL for >3  months. And PTLD occurred in 3 of the 18 patients (10.7%) (2 were seronegative and 1 seropositive at transplantation).  These patients recovered with rituximab and kidney function was maintained. Rituximab regimen was given to 15/28 (53.7%) patients with refractory EBV viremia, 375 dose mg/m2  weekly for 1-4 doses per course. Complete resolution was achieved in 12/15 patients (80%) following the second dose of rituximab.No child developed PTLD post rituximab. Rituximab treatment was related with hypogammaglobulinemia in 7 patients and an allergic reactionin 1 patient. There was no graft loss due to refractory EBV. One death occurred in a child who have not used Rituksimab due to unrelated reasons.
Conclusion: EBV viremia poses a significant challenge in pediatric kidney transplant recipients. The standard of care treatment with reduction of immunosuppression and Valganciclovir has not prevented the development of refractory EBV viremia, Rituximab might be an effective treatment in this group. Rituximab is associated with side effects such as hypogammaglobinemia, which should be monitored.