EBV DNAemia following Rituximab treatment: Insights from a case series
Auda Plaud Gonzalez1,2, Patricia Rodriguez Reyes2, Marycarmen Flores Claudio2, Nilka De Jesus Gonzalez1,2.
1Department of Pediatrics, Division Nephrology, University of Puerto Rico, San Juan, Puerto Rico; 2Pediatric Kidney Transplant Program, Hospital Auxilio Mutuo, San Juan, Puerto Rico
Background: EBV DNAemia has been associated with PTLD specially in high-risk (HR) patients. Many pediatric patients are considered HR due to being naive. Reports from small cohorts have described the use of Rituximab to treat DNAemia. We describe a cohort of pediatric kidney transplant (PKT) patients who received Rituximab and its impact on EBV DNAemia.
Methods: Retrospective chart review of PKT recipients who received Rituximab for any indication at a single PKT program between 1/2018 and 12/2023. We screen EBV as follows: monthly PCR for the first 6-months post-transplant, every 3-months from months 7-36, and every 6-months thereafter. For patients receiving Rituximab, EBV screening is performed monthly for 6-months, followed by testing every 3-months. The primary outcome was EBV DNAemia post-Rituximab irrespective of DNAemia status prior. Descriptive statistics were used.
Results: During the study period, eight pediatric kidney transplant recipients received Rituximab: five for biopsy-proven ABMR, two for elevated DSAs, and one for PTLD. All patients received one dose of Rituximab of 375 mg/m2, at PKT median 65-months (1.4-207). CD19 0% one month after Rituximab. All patients were kept on enhanced triple therapy Immunosuppression after Rituximab, except the patient who developed PTLD, modified to account for chemotherapy. Three patients had EBV viremia prior to Rituximab administration. Their EBV serostatus was as follows: one D+/R+, one D+/R-, and one with an unknown donor serostatus (DUNK/R+). From these patients, the one with high risk for EBV (D+/R-) developed PTLD and received Rituximab as part of treatment. In all three cases, EBV viremia resolved within one month, with no recurrence over follow-up periods of 2-6 years. The peak EBV viremia levels were 82,000 IU/ml (D+/R-), 2431 copies/uL (D+/R+), and 2442 copies/uL(DUNK/R+). Among the five patients without prior EBV viremia, two were EBV D+/R+, one EBV DUNK/R+ and two EBV D+/R-. None of them developed EBV viremia after Rituximab at 1-6 yr. No deaths occur during the follow up period and graft function remained stable in all patients.
Conclusions: In this case series, there was no evidence of EBV DNAemia following Rituximab in patients with prior EBV viremia, with follow-up ranging from 2 to 6 years post-treatment. Additionally, patients without pre-existing EBV viremia who received Rituximab did not develop EBV DNAemia during follow-up (1-6 years post-Rituximab). Larger cohort is needed to validate these observartions and propose evidence based clinical practice guidelines.
[1] PTLD
[2] EBV