The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring

Jutta Preiksaitis, Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Upton Allen, Division of Infectious Diseases and the Transplant and Regenerative Medicine Center, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Hospital, The George Washington University, Washington, District of Columbia, USA.
Vikas R. Dharnidharka, Department of Pediatrics, Division of Pediatric Nephrology, Hypertension & Pheresis, Washington University School of Medicine & St. Louis Children's Hospital, St. Louis, Missouri, USA.
Daniel E. Dulek, Division of Pediatric Infectious Diseases, Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Michael Green, Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Olivia M. Martinez, Department of Surgery and Program in Immunology, Stanford University School of Medicine, Stanford, California, USA.
Diana M. Metes, Departments of Surgery and Immunology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Marian G. Michaels, Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Françoise Smets, Pediatric Gastroenterology and Hepatology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Richard E. Chinnock, Loma Linda University Children's Hospital, Loma Linda, California, USA.
Patrizia Comoli, Cell Factory & Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico, Pavia, Italy.
Lara Danziger-Isakov, Division of Infectious Disease, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Anne I. Dipchand, Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Carlos O. Esquivel, Stanford University School of Medicine, California, USA.
Judith A. Ferry, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Thomas G. Gross, Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, Colorado, USA.
Robert J. Hayashi, Division of Pediatric Hematology/Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri, USA.
Britta Höcker, University Children's Hospital, Pediatrics I, Heidelberg, Germany.
Arnaud G. L'Huillier, Faculty of Medicine, Pediatric Infectious Diseases Unit and Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland.
Stephen D. Marks, Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
George Vincent Mazariegos, Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
James Squires, Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Steven H. Swerdlow, Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ralf U. Trappe, Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Bremen, Germany.
Gary Visner, Division of Pulmonary Medicine, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Steven A. Webber, Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
James D. Wilkinson, Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
Brtitta Maecker-Kolhoff, Hannover Medical School, Pediatric Hematology and Oncology, Hannover, Germany.

Document Type

Journal Article

Publication Date

2-1-2024

Journal

Pediatric transplantation

Volume

28

Issue

1

DOI

10.1111/petr.14471

Keywords

Epstein-Barr virus; PTLD; biomarkers; child; solid organ transplantation

Abstract

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

Department

Pediatrics

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