Decreasing Incidence of Symptomatic Epstein-Barr Virus Disease and Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplant Recipients: Report of the Studies of Pediatric Liver Transplantation Experience

Authors

  • Michael R. Narkewicz,

    Corresponding author
    1. Children's Hospital Colorado, Aurora, CO
    • Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
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  • Michael Green,

    1. Departments of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
    2. Pediatrics, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
    3. Children's Hospital, Pittsburgh, PA
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  • Stephen Dunn,

    1. Divison of Pediatric Solid Organ Transplantation, Department of Surgery, Thomas Jefferson University School of Medicine, Wilmington, DE
    2. Nemours Children's Hospital, Wilmington, DE
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  • Michael Millis,

    1. Section of Transplantation, Department of Surgery, University of Chicago Medical Center, Chicago, IL
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  • Susan McDiarmid,

    1. Departments of Pediatrics, University of California Los Angeles School of Medicine, Los Angeles, CA
    2. Surgery, University of California Los Angeles School of Medicine, Los Angeles, CA
    3. Matel Children's Hospital, Los Angeles, CA
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  • George Mazariegos,

    1. Departments of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
    2. Children's Hospital, Pittsburgh, PA
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  • Ravinder Anand,

    1. Emmes Corporation, Rockville, MD
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  • Wanrong Yin,

    1. Emmes Corporation, Rockville, MD
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  • and for the Studies of Pediatric Liver Transplantation Research Group


  • Studies of Pediatric Liver Transplantation is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant U01-DK061693-01A1) and by Astellas Pharma US, Inc., and Roche Laboratories (an unrestricted grant). The centers, investigators, and coordinators composing the Studies of Pediatric Liver Transplantation Research Group are listed in the supporting information.

Address reprint requests to Michael R. Narkewicz, M.D., Children's Hospital Colorado, 13123 East 16th Avenue, B290, Aurora, CO 80045. Telephone: 720-777-6669; FAX: 720-777-7277; E-mail: michael.narkewicz@childrenscolorado.org

Abstract

Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT). Objective: Describe the incidence of PTLD and symptomatic Epstein-Barr virus (SEBV) disease in a large multicenter cohort of children who underwent LT with a focus on the risk factors and changes in incidence over time. SEBV and PTLD were prospectively determined in 2283 subjects who had undergone LT for the first time with at least 1 year of follow-up in the Studies of Pediatric Liver Transplantation database. SEBV was defined with specific criteria, and PTLD required tissue confirmation. The incidence of SEBV and PTLD was determined with a Kaplan-Meier analysis. Univariate and multivariate modeling of risk factors was performed with standard methods. SEBV occurred in 199 patients; 174 (87.4%) were EBV–negative at LT. Seventy-five patients developed PTLD, and 64 (85.3%) of these patients were EBV-negative at LT. Among the 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV by the second year after LT, and 2.8% developed PTLD. There were lower rates of SEBV (5.9% versus 11.3%, P < 0.001) and PTLD (1.7% versus 4.2%, P = 0.001) in 2002-2007 versus 1995-2001. In 2002-2007, tacrolimus and cyclosporine trough blood levels in the first year after LT were significantly lower, and fewer children were receiving steroids. Biliary atresia, and recipient EBV status were correlated. In a multivariate analysis, era of LT, recipient EBV status, and frequent rejection episodes were associated with SEBV and PTLD. The incidence of SEBV and PTLD is decreasing in pediatric LT recipients concomitantly with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD. Liver Transpl 19:730–740, 2013.. © 2013 AASLD.

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