Quantitative Monitoring of EBV Viral Load in 222 Hematopoietic Stem Cell Transplant Patients: Risk Analysis and Development of EBV-Associated Post-Transplant Lymphoproliferative Diseases (PTLD)

Abstract 3018

Background and Purposes Epstein-Barr virus (EBV)-associated PTLD is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Independent risk factors include use of ATG, acute GVHD, CMV antigenemia, T-depleted graft, and unrelated donor in our previous study. Quantitative real-time polymerase chain reaction (Q-PCR) was developed for early detection and intervention of EBV reactivation to prevent PTLD-related mortality.

Patients and Methods Between Apr 2004 and Oct 2010, EBV viral load in plasma was monitored by Q-PCR in 222 HSCT patients (total 2945 samples) in NTUH. EBV reactivation was defined as > 500 copies/mL in two consecutive assays or > 10-fold elevation than baseline level.

Results EBV reactivation occurred in 50 (22%) patients. The cumulated incidence of EBV reactivation was 28% at 1-year and 32% at 2-year. Median time to EBV reactivation was 40 days (ranges, 26–406) after SCT and median peak EBV-viral load, 10888 copies/ml (ranges, 948–3×10⁷). The risk of EBV reactivation was significantly higher in patients receiving ATG (52% vs. 13%, p< 0.001), use of TBI (58% vs. 26%, p<0.001), mismatched donor (69% vs. 27%, p<0.001), CMV reactivation (44% vs. 19%, p<0.001) in univariate analysis. In multivariate analysis, independent risk factors include: ATG use (HR 5.44, p<0.001), TBI (HR 3.52, p<0.001), and Fludara-based conditioning (HR 3.16, P=0.01). PTLD developed in 8 patients (5%) who didn't monitor EBV viral load regularly, and two were dead.

Conclusions Monitoring of EBV viral load is a sensitive and useful tool in the surveillance of EBV-reactivation. Frequent monitoring in high-risk patients is important to prevent occurrence of EBV-PTLD.