Significance of Persistent EBV Viral Load in Pediatric Heart Transplant Recipients

Abstract

PurposeAs most cases of post-transplant lymphoproliferative disorder (PTLD) are driven by EBV, most centers monitor EBV viral load (VL) by quantitative PCR. Optimal treatment for patients (pts) with persistent EBV VL is unknown. Aim: To determine the outcome of reduced immunosuppression (IS) and anti-viral therapy on the frequency of PLTD and acute rejection (AR) in pediatric heart transplant (Tx) recipients.Methods and MaterialsWe reviewed medical records of 113 pts whose EBV serostatus was known at Tx. We ascertained their EBV PCR VL, IS regimen, anti-viral therapy, CT/PET scan and biopsy results, and AR episodes. Whole blood PCR was used for EBV VL monitoring. Pts were divided into 3 groups based on EBV VL: not detected (ND) (<1000), low (1000-10,000) and high (>10,000) copies/ml. Pts who had persistently high VL twice within 2 months underwent whole body CT/PET imaging to exclude PTLD. Diagnosis of PTLD was based on histopathology findings of abnormal lymphoid proliferation and positive in situ hybridization using EBER probe for EBV.ResultsThe findings of this study are shown in Figure. Abnormal CT/PET scan concerning for PTLD was observed in 66% in EBV naïve heart Tx recipients who had high VL. Of 10 pts who had abnormal PET/CT scan, 3 had PTLD on biopsy. Antiviral therapy was initiated in 4 pts who showed only temporary decrease in VL. Reduction in IS in pts with high VL resulted in AR in 3 cases. [figure 1]ConclusionsPediatric heart Tx recipients with high EBV VL are at risk for PTLD despite reduction in IS. We recommend frequent surveillance of the allograft for AR with IS reduction. Multicenter study is needed to focus on strategies not only to prevent PTLD, but also to protect the allograft. As most cases of post-transplant lymphoproliferative disorder (PTLD) are driven by EBV, most centers monitor EBV viral load (VL) by quantitative PCR. Optimal treatment for patients (pts) with persistent EBV VL is unknown. Aim: To determine the outcome of reduced immunosuppression (IS) and anti-viral therapy on the frequency of PLTD and acute rejection (AR) in pediatric heart transplant (Tx) recipients. We reviewed medical records of 113 pts whose EBV serostatus was known at Tx. We ascertained their EBV PCR VL, IS regimen, anti-viral therapy, CT/PET scan and biopsy results, and AR episodes. Whole blood PCR was used for EBV VL monitoring. Pts were divided into 3 groups based on EBV VL: not detected (ND) (<1000), low (1000-10,000) and high (>10,000) copies/ml. Pts who had persistently high VL twice within 2 months underwent whole body CT/PET imaging to exclude PTLD. Diagnosis of PTLD was based on histopathology findings of abnormal lymphoid proliferation and positive in situ hybridization using EBER probe for EBV. The findings of this study are shown in Figure. Abnormal CT/PET scan concerning for PTLD was observed in 66% in EBV naïve heart Tx recipients who had high VL. Of 10 pts who had abnormal PET/CT scan, 3 had PTLD on biopsy. Antiviral therapy was initiated in 4 pts who showed only temporary decrease in VL. Reduction in IS in pts with high VL resulted in AR in 3 cases. [figure 1] Pediatric heart Tx recipients with high EBV VL are at risk for PTLD despite reduction in IS. We recommend frequent surveillance of the allograft for AR with IS reduction. Multicenter study is needed to focus on strategies not only to prevent PTLD, but also to protect the allograft.