Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients

Background: Post-transplant lymphoproliferative disease (PTLD) is a severe complication in transplant recipients. Detection of increased Epstein-Barr viral (EBV) load in the peripheral blood acts as a surrogate marker for increased risk,of PTLD development. We prospectively monitored EBV load, immunosuppression and PTLD in pediatric heart transplant (HTx) patients to determine risk factors for an increased EBV load and risk of PTLD. Methods: Forty-one pediatric heart transplant recipients were included and under-went prospective monitoring of their immunosuppression and ethylene-diamine tetraacetic acid (EDTA) blood sampling for EBV load (copies/mu g DNA) measurement using quantitative real-time polymerase chain reaction (PCR; TaqMan) during January 2001 to December 2006. Results: EBV load was measurable in 70% and was significantly increased (>2,000 copies/mu g DNA) in 35% of the patients, with a median EBV load of 5,100 (range 0 to 50,665 copies/mu g DNA). Increased EBV load was detected in patients receiving CsA-azathioprine or more than two doses of anti-thymocyte globutin (ATG) and in those <10 years of age, without any significant differences in CsA blood levels. Lowest or negative EBV load was measured in patients receiving CsA-mycophenolate mofetil (MMF) or CsA only. CsA blood levels were not predictable for increased EBV load or PTLD. Six patients developed a EBV-associated B-cell lymphoma (PTLD), among whom 4 (67%) were receiving CsA-azathioprine. Conclusions: Frequent EBV load monitoring identifies patients at high risk for PTLD development. Azathioprine and ATG are major risk factors for increased EBV load and PTLD and patients may benefit from a change of immunosuppression in addition to pre-emptive anti-viral or anti-tumor strategies.