Open Access, Peer-reviewed
pISSN 2384-1079
eISSN 2384-1087
    Pediatr Infect Vaccine. 2017 Apr;24(1):44-53. Korean.
    Published online Apr 18, 2017.
    https://doi.org/10.14776/piv.2017.24.1.44
    Copyright © 2017 The Korean Society of Pediatric Infectious Diseases
    Original Article

    Clinical Utility of Epstein-Barr Viral Load Assay to Diagnose Posttransplant Lymphoproliferative Disorders in Pediatric Heart Transplant Recipients

    Joonil Kim, Jina Lee, and Young-Hwue Kim
      • Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, the Republic of Korea.
    • Corresponding author (Email: entier@amc.seoul.kr )
    Received September 07, 2016; Revised October 20, 2016; Accepted October 21, 2016.

    Abstract

    Purpose

    The aim of this study was to investigate the risk factors for posttransplant lymphoproliferative disorder (PTLD) and to evaluate the association between Epstein-Barr viral load and the development of PTLD in pediatric heart transplant recipients.

    Methods

    We reviewed children aged <18 years who underwent heart transplantation and quantitative analysis of blood Epstein-Barr virus (EBV) viremia at our institute from January 2006 to March 2015. Clinical characteristics and EBV viral loads were compared according to the presence of PTLD.

    Results

    Over 9 consecutive years, a total of 40 heart transplant recipients, were included. Among 28 children with available EBV viral load measurements, seven patients (25%) had EBV viremia only defined as at least one time of ≥457 copies/mL. PTLD occurred in three recipients (7.5%) 4.3, 6.3, and 17.0 months after transplant and all PTLD cases had preceding EBV viremia. The median age at transplant was 5.3 years (range, 0.5 to 6.0 years) in the PTLD group, compared with 11.9 years (range, 0.3 to 17.8 years) in the non-PTLD group (P=0.021). The median values of the peak EBV levels in the PTLD group were 3,452,170 copies/mL (range, 46,750 to 7,622,910 copies/mL); the peak EBV levels in the non-PTLD group were 3,112 copies/mL (range, 2,250 to 103,000 copies/mL).

    Conclusions

    Younger age at transplant and presence of EBV viremia were associated with the development of PTLD in pediatric heart transplant recipients. A prospective study will be required to determine the blood EBV load for predicting the development of PTLD in these patients.

    Keywords
    Lymphoproliferative disorders; Heart transplantation; Herpesvirus 4, human; Child

    Figures

    Fig. 1
    Flowchart for the selection of study population. The underlying diseases for heart transplantation were as follows: dilated cardiomyopathy (n=25), hypertrophic cardiomyopathy (n=4), restrictive cardiomyopathy (n=4), congenital heart disease (n=7), and acute idiopathic pneumonitis (n=1).*Multiple organ transplant included heart-lung transplant (n=1); †Presence of EBV viremia was defined as at least one time of ≥457 EBV copies/mL of whole blood. Abbreviations: EBV, Epstein-Barr virus; PCR, polymerase chain reaction; PTLD, posttransplant lymphoproliferative disorder.

    Fig. 2
    Positron emission tomography (PET) findings of all three patients diagnosed with posttransplant lymphoproliferative disorder. (A) Focal hypermetabolic lesion was noted in the liver (segment IV), right kidney, and posterior nasopharyngeal wall in patient no. 1. (B) After 4 months of treatment, complete metabolic response of lymphomatous involvement in the PET was observed in patient no. 1. (C) Diffuse hypermetabolic activity of the spleen was noted with reactive hyperplasia in cervical lymph nodes and palatine tonsils in patient no. 2. (D) After 5 months of treatment, the normalized spleen in the PET was observed in patient no. 2. (E) Multiple hypermetabolic enlarged lymph nodes in bilateral cervical lymph nodes, left retropharygeal area, both supraclavicular area, aortocaval areas, and the spleen in patient no. 3. (F) After 12 months of treatment, no significant change of hypermetabolic lesions in multiple lymph nodes was observed in patient no. 3.

    Fig. 3
    Lymph node biopsy demonstrated a polymorphic posttransplant lymphoproliferative disorder (patient no. 3). (A) Polymorphic infiltrate in the paracortex with a preserved nodal architecture (H&E stain, ×40). (B) The lymphoid cells vary in size and shape and degree of transformation. Atypical immunoblasts are predominantly seen in the mixture of cells (H&E stain, ×400). (C) Many of the cells are positive for Epstein- Barr virus (EBV) via in situ hybridization for EBV-encoded messenger RNA (×100). (D) Many cells express the CD20 B-cell marker (×40).

    Tables

    Table 1
    Clinical and Demographic Characteristics of Heart Transplant Recipients according to the Presence or Absence of PTLD

    Table 2
    Clinical Characteristics for the Patients Who Developed PTLD

    Table 3
    EBV Viral Load among Recipients Who Developed Any Level of EBV Viremia according to the Presence or Absence of PTLD

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    MeSH Terms
    Child
    Heart Transplantation
    Heart*
    Herpesvirus 4, Human
    Humans
    Lymphoproliferative Disorders*
    Prospective Studies
    Risk Factors
    Transplant Recipients*
    Viral Load*
    Viremia
    Metrics
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