Introduction: Post transplant lymphoproliferative disease (PTLD) is a devastating complication of immunosuppression. Epstein-Barr virus (EBV) DNAemia is reported in 29%-31% of adult renal transplant recipients, preceding PTLD in 90% of cases. Rituximab depletes B-lymphocytes, the EBV reservoir, and is indicated in hematopoietic stem cell transplantation (HSCT) for prevention of PTLD. In solid organ transplantation (SOT) with EBV-DNAemia there is lack of evidence-based guidelines regarding PTLD prevention. Efficacy of antivirals and IVIG remains controversial. We report our ten-year experience (2012-2022) with prophylactic rituximab therapy in five of 60 pediatric renal transplant recipients (PRTR) with increasing EBV load unresponsive to immunosuppressive reduction.
Methods: Immunosuppressive regimen included basiliximab and glucocorticoids induction, followed by glucocorticoids, mycophenolate mofetil (MMF) and tacrolimus maintenance. Blood EBV load surveillance was routinely performed using real-time polymerase chain reaction (RT-PCR), every two weeks during the first year post transplantation, and monthly thereafter. Patients with EBV DNAemia were tested weekly, and managed with MMF dose reduction, followed by MMF cessation if persistent. Increasing EBV load albeit MMF cessation was managed with four weekly doses of rituximab, 375mg/m2/dose. Prior to rituximab therapy, all patients underwent clinical evaluation to exclude PTLD.
Results: Within the study period, EBV DNAemia was detected 120-720 days post transplantation, in seven of 60 PRTR (12%), during eight separate episodes. Viral loads ranged between 3000-30000 copies/ml. All patients were under stable maintenance immunosuppression prior to EBV detection. Three episodes of EBV-DNAemia were preceded by other intercurrent viral infections. All patients with EBV-DNAemia showed stable renal and liver function, normal blood counts, and no evidence of PTLD. MMF dose reduction/cessation resulted in EBV clearance in two patients (previously EBV seropositive). There were no episodes of graft rejection following immunosuppressive reduction. Five patients (71%, previously EBV seronegative), suffered from six episodes of increased EBV-load unresponsive to MMF cessation, and were given rituximab. All rituximab-treated patients showed EBV clearance within 7-45 days from therapy initiation. Rituximab adverse effects included cytopenia (leukopenia-70%, anemian-30%). Patients showed no serious infections or graft dysfunction.
Conclusions: Although EBV DNAemia is relatively common in renal transplant recipients (29%-48.5%), its prevalence in our cohort was lower (12%). EBV-naïve patients showed increased risk for post-transplantation EBV-DNAemia, and were less likely to clear EBV in response to immunosuppressive reduction. None of our patients with EBV-DNAemia developed PTLD. We suggest that rituximab therapy is safe and effective for EBV clearance in PRTR with persistent EBV-DNAemia, who are unresponsive to immunosuppressive dose reduction.