Related Experiment Videos
Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in
1Department of Pediatrics, Children's Hospital of Pittsburgh, The Thomas Starzl Transplantation Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
Insights
Persistent low Epstein-Barr virus (EBV) viral loads after intestinal transplantation (ITx) predict no posttransplant lymphoproliferative disease (PTLD). Monitoring frequency can be reduced for these low-risk patients.
Area of Science:
- Transplantation Immunology
- Virology
- Oncology
Background:
- Elevated Epstein-Barr virus (EBV) viral load correlates with posttransplant lymphoproliferative disease (PTLD) risk.
- Serial EBV viral load monitoring guides preemptive therapy (PT) for PTLD.
- Optimal monitoring frequency and predictive value for low viral loads remain unclear.
Purpose of the Study:
- To evaluate the predictive negative value of EBV viral load monitoring in pediatric intestinal transplant (ITx) recipients.
- To determine if low or undetectable EBV viral loads can safely reduce monitoring frequency.
Main Methods:
- Serial peripheral blood EBV viral load monitoring using quantitative competitive PCR in 30 ITx children.
- Defined thresholds for high EBV viral load (>40 or >200 genome copies/10(5) lymphocytes) to guide preemptive therapy (PT).
- Assessed PTLD development in relation to EBV viral load trends and PT administration.
Main Results:
- 12/30 patients with persistently low EBV viral loads (<40) never received PT and developed no PTLD.
- 18/30 patients had at least one high EBV viral load (> or =200), with PTLD developing in 5/18.
- All PTLD cases occurred in EBV seropositive recipients with high viral loads within 3 months post-ITx.
Conclusions:
- Persistently low or undetectable EBV viral loads offer 100% negative predictive value for PTLD post-ITx.
- Patients with low EBV loads for the first 6 months post-ITx are at minimal risk for PTLD.
- Monitoring frequency can be safely decreased for ITx patients with sustained low EBV viral loads.
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.