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Chronic High Epstein‐Barr Viral Load State and Risk for Late‐Onset Posttransplant Lymphoproliferative Disease/Lymphoma in Children

Increased use of serial EBV‐PCR monitoring after pediatric transplantation has led to the identification of asymptomatic patients who carry very high viral loads over prolonged periods. The significance of this high‐load state is unknown. We speculated that this state may identify patients at high risk for development of late PTLD/lymphoma. We reviewed data on 71 pediatric heart recipients who had serial viral load monitoring since 1997. Chronic high‐load state was defined as the presence of >16 000 genome copies/mL whole blood on ≥50% of samples over at least 6 months. Among 20 high‐load carriers (eight following prior PTLD, seven with prior symptomatic EBV infection, five without previous EBV disease), 9 (45%) developed late‐onset PTLD 2.5–8.4 years posttransplant (including with four Burkitt's lymphoma). Among 51 controls with low (n = 39) or absent (n = 12) loads, only 2 (4%; p < 0.001 absent/low vs. high load) developed late PTLD/lymphoma. By multivariable analysis, high‐load carrier state (OR = 12.4, 95% CI 2.1–74.4) and prior history of PTLD (OR = 10.7, 95% CI 1.9–60.6) independently predicted late PTLD. A chronic high EBV‐load state is not benign and is a predictor of de novo or recurrent PTLD.