Epidemiology and outcome of chronic high Epstein‐Barr viral load carriage in pediatric kidney transplant recipients

Abstract

The development of EBV infection and PTLD is normally associated with a high EBV viral load in peripheral blood. Observations have previously identified existence of a CHL carrier state that demonstrated variable outcomes based upon the organ which was transplanted. Data defining the incidence and outcome of CHL in pediatric KTx are not well described. The charts of children undergoing isolated KTx at Children's Hospital of Pittsburgh between January 2000 and December 2014 were retrospectively reviewed. EBV loads in the peripheral blood were routinely measured as part of surveillance protocols at our center. CHL was defined as the presence of high load for >50% of samples for ≥6 months. PTLD was defined histologically using WHO definitions. Of 188 isolated KTx recipients, we identified a total of 16 (8%) children who developed CHL carrier state. No patient developed EBV-driven late-onset PTLD. Age at the time of KTx was significantly lower in the CHL group (median 3.9 years, interquartile range: IQR 2.9-6.6, P = .0004). Children in the CHL group were more likely to be EBV-seronegative prior to KTx (94%, 15/16), compared to the UVL and LVL groups (55% and 50%, respectively, P < .002). The median duration of CHL carrier state was 20 months (IQR 10.7-35.8). Fifteen of the 16 CHL carriers experienced spontaneous resolution of CHL carrier state. Children in the CHL group were younger at the time of primary EBV infection (P = .023). Finally, antiviral medication was not effective in either preventing or decreasing the EBV viral load in blood (P = .84). Overall incidence of late-onset PTLD is very low compared to heart and intestinal transplant, even though KTx recipients can develop CHL carrier state. The CHL carriers in KTx recipients were EBV-seronegative prior to transplant and were younger both at the time of KTx and at the time of primary EBV infection compared to those in the UVL and HVL groups. Antivirals did not prevent EBV infection or decrease EBV viral loads.

Use of Rituximab for persistent EBV DNAemia, and Its effect on donor‐specific antibody development in pediatric renal transplant recipients: A case series

“…The incidence of PTLD was 45% in persistent high load carriers in a cohort of heart transplant recipients 8 . The same center reported that the incidence is lower in liver transplant (3%) and intestinal transplant (11%) recipients and lowest in kidney transplant patients(0%) 16‐18 A subset analysis from a prospective randomized double blind trial of steroid withdrawal, conducted by the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), showed a 6.9% incidence of PTLD in patients with persistent viral load 19 . In our study, 1 (No‐Rituximab patient) of 13 (7.6%) patient with PEBV developed PTLD, which is consistent with the above reported PTLD rate.…”

Epstein-Barr virus-associated monomorphic post-transplant lymphoproliferative disorder after pediatric kidney transplantation: A case report

“…Some studies suggest that an organ recipient’s EBV load should be monitored every 2 wk for the first 3 mo after surgery, and then every month for the second 3 mo, followed by every 3 mo for the last 6 mo[ 8 ]. However, there is no clear evidence that antiviral therapy helps to reduce a patient’s EBV load or prevent EBV infection[ 9 ].…”

Common and Emerging Infections in Pediatric Transplant Recipients

“…In pediatric heart transplant recipients, the highest rates of PTLD occurred in children transplanted at 1-10 years of age [36]. Interestingly, data from pediatric renal and liver transplant patients identified that EBV seronegative children were more likely to have chronically high viral loads than their seropositive counterparts, but the presence of high viral loads did not correlate with subsequent development of PTLD [39,40].…”