Epstein-Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based immunosuppression

In children undergoing renal transplantation, Epstein-Barr virus- (EBV) rel ated disorders, including posttransplant lymphoproliferative disorder, cons titute a major complication associated with tacrolimus-based immunosuppress ion, In this study, we reviewed the EBV complications in 81 children, all o f whom had EBV serological studies before renal transplantation, We also hi ghlight the data in a subgroup of 30 children transplanted more recently wh o were monitored sequentially for EBV symptoms and signs and with immunolog ical studies, and in whom the donor EBV serology was also determined. During a mean follow-up time of 3.9+-2.3 years, 19 children developed sympt omatic Epstein-Barr virus (EBV*) infection. This consisted of the clinical syndrome of infectious mononucleosis in 7 children; in addition, 10 childre n developed posttransplant lymphoproliferative disorder (PTLD), which was h istologically confirmed in 8, and 2 others developed malignant lymphoma. Re cipient seronegativity (EBV-) and donor EBV seropositivity (EBV+) predicted a high probability for seroconversion (P=0.0072) and for developing PTLD o r malignancy (P<0.01), In the subgroup of 30 children studied prospectively , seroconversion occurred in 15 of 19 seronegative recipients of EBV seropo sitive grafts at 6.6+/-2.6 months (mean+/-SD) after transplantation. Seven children developed symptomatic EBV infection (including three with PTLD) in association with seroconversion and a rise in EBV viral load in the periph eral blood, demonstrated by an EBV-specific polymerase chain reaction (EBV- PCR), Of 15 seroconverters, 7 who developed symptomatic infection had recei ved EBV+ grafts; 8 others with EBV+ grafts seroconverted but did not become symptomatic. These two subgroups did not differ in age, rejection rate, an tiviral prophylaxis, or level of immunosuppression, In the overall group of 81 children, only the two with malignant lymphoma w ho were managed with chemotherapy had substantial morbidity, The 10 individ uals with PTLD received a regimen combining i.v. ganciclovir and CytoGam, a nd stopping or reducing the tacrolimus, Pour children with associated marke d tonsilar growth underwent tonsillectomy, All 19 individuals with EBV diso rders resolved their symptoms and signs, and all have maintained good allog raft function during a follow-up time of 3.0+/-2.5 years (mean+/-SD) after the development of symptomatic EBV infection PTLD, or malignancy. We conclude that seronegative recipients of EBV+ grafts are at high risk fo r developing EBV-related disorders after renal transplantation under tacrol imus-based immunosuppression, although the ultimate clinical outcomes have been remarkably good. These data form the basis for formulating strategies for early identification of children at risk for EBV complications, and for instituting preventive and treatment strategies that permit these children to realize the substantial benefits offered by tacrolimus-based immunosupp ression.