Decreasing Incidence of Symptomatic Epstein-Barr Virus Disease and Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplant Recipients: Report of the Studies of Pediatric Liver Transplantation Experience

Abstract

Post transplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT). Objective Describe the incidence of PTLD and symptomatic Epstein Barr virus disease (SEBV) in a large multicenter cohort of children who have undergone LT focused on the risk factors and changes in incidence over time. Methods Prospective determination of SEBV and PTLD in 2283 subjects who had undergone a first LT with at least 1 year of follow up in the Studies of Pediatric Liver Transplantation database. SEBV was defined by specific criteria and PTLD required tissue confirmation. Incidences of SEBV and PTLD were determined by Kaplan Meier. Univariate and multivariate modeling of risk factors were performed using standard methods. Results SEBV occurred in 199, of whom 174 (87.4%) were EBV negative at LT. 75 patients developed PTLD of whom 64 (85.3%) were EBV negative at LT. Of 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV and 2.8% PTLD by the second year post-LT. There was a lower incidence of SEBV (11.3% vs 5.9, p<0.0001) and PTLD (4.2 vs. 1.7, p=0.0011) in 2002-07 compared to 1995-2001. Tacrolimus and cyclosporine trough blood levels in the first year post transplant were significantly lower and fewer children were receiving steroids in 02-07. Era of LT, EBV negative recipient status, younger age, biliary atresia and frequent rejection episodes were associated with an increased risk for SEBV and PTLD in univariate analysis. Age, biliary atresia and EBV recipient status were correlated. In multivariate analysis era of LT, EBV recipient status and frequent rejection episodes was associated with SEBV and PTLD. Conclusions The incidence of SEBV and PTLD is decreasing in pediatric LT recipients coincident with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD.

Posttransplantation lymphoproliferative disorder after pediatric solid organ transplantation: experiences of 20 years in a single center

“…For early detection and furthermore prevention of PTLD, monitoring EBV viral load is considered as one of the crucial factors, even though the specificity and positive predictive value of EBV titer in predicting PTLD are still controversial24252627). As an example, right after that regular EBV viral load monitoring was adopted as standard clinical practice, our center encountered only one case of pediatric PTLD during 2008–2012; Upon recognition of high titer of EBV of >10,000 copies/mL immunosuppression was reduced when possible, and active surveillance of PTLD was adopted.…”

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“…Furthermore, of those patients who developed posttransplant lymphoproliferative disease, all but 1 patient in each group were positive for Epstein-Barr virus at the time of transplant. Among the risks factors associated with posttransplant lymphoproliferative disease after liver transplant, Narkewicz and associates 18 found that ACR is associated with increased risk of posttransplant lymphoproliferative disease, likely due to the increased amount of immunosuppression that has to be administered. With the use of rATG, we demonstrated a significantly decreased rate of ACR, which could explain the lower incidence of posttransplant lymphoproliferative disease in this group.…”

Cutaneous involvement of polymorphic post‐transplant lymphoproliferative disorder in a child after liver transplantation

“…The primary risk factors for PTLD are recipient EBV‐naïve status, higher levels of immunosuppression, type of allograft, and recipient's age . The risk of developing PTLD is reported to be intermediate (1%‐12%) in liver transplantation among all SOTs due to lower levels of immunosuppression required and less amount of lymphoid tissue involved .…”