Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in children

Abstract

Background: The correlation between an elevated Epstein-Barr virus (EBV) viral load in the peripheral blood and the subsequent development of EBV-associated posttransplant lymphoproliferative disease (PTLD) is the basis for strategies using serial measurements of the EBV viral load to guide preemptive therapy (PT). Neither the frequency, duration of monitoring, nor the predictive negative value of viral load monitoring for asymptomatic patients with persistent low or nondetectable viral loads against the development of PTLD has been established.

Methods: Since April 1994, children undergoing intestinal transplantation (ITx) underwent serial monitoring of the EBV viral load in their peripheral blood using a quantitative competitive EBV polymerase chain reaction assay (PCR). Samples were obtained every 2 weeks for the first 3 months and then every 1-3 months depending on the patients clinical condition. EBV viral loads > or =40 (for patients who were EBV seronegative pre-ITx) and > or =200 (for those who were seropositive) genome copies/10(5) peripheral blood lymphocytes were felt to identify patients at increased risk for PTLD and generally prompted PT.

Results: A total of 30 ITx recipients were compliant with our monitoring protocol; 23/30 are alive 6-59 months post-ITx. A total of 12/30 never had a viral load >40 and did not receive PT. In contrast, 18/30 had > or =1 high viral load (> or =200); the first high viral load was measured a median of 59 days post-ITx (range 1-440). A late rise (>6 months post-ITx) was seen in only 2/18 children. A total of 0/12 patients with persistently low viral loads received PT and none developed PTLD. In contrast, 5/18 with > or =1 one high viral load (including 2/14 who received and 3/4 who did not receive PT) developed PTLD. All five children with PTLD were EBV seropositive pre-ITx and experienced their first high EBV PCR within the first 3 months after ITx.

Conclusions: The predictive negative value of persistently low or nondetectable EBV viral loads was 100% in this study. Patients with nondetectable or low viral loads for the first 6 months after ITx did not develop PTLD regardless of their pretransplant EBV serological status. The frequency of viral load monitoring can be safely decreased for patients whose viral loads remain low for the first 6 months ITx.