Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium

Pediatr Transplant. 2024 May;28(3):e14743. doi: 10.1111/petr.14743.

Abstract

Background: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia.

Methods: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab.

Results: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons.

Conclusions: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.

Keywords: Epstein–Barr virus; kidney transplant; pediatrics; post‐transplant lymphoproliferative disorder; rituximab.

MeSH terms

  • Child
  • Child, Preschool
  • DNA, Viral
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / drug therapy
  • Epstein-Barr Virus Infections* / prevention & control
  • Herpesvirus 4, Human / genetics
  • Humans
  • Kidney Transplantation* / adverse effects
  • Lymphoproliferative Disorders* / drug therapy
  • Lymphoproliferative Disorders* / etiology
  • Lymphoproliferative Disorders* / prevention & control
  • Nephrology*
  • Rituximab / therapeutic use
  • Transplant Recipients
  • Viral Load

Substances

  • Rituximab
  • DNA, Viral