Browse > Article
http://dx.doi.org/10.14776/piv.2017.24.1.44

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

Kim, Joonil (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
Lee, Jina (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
Kim, Young-Hwue (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
Publication Information
Pediatric Infection and Vaccine / v.24, no.1, 2017 , pp. 44-53 More about this Journal
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 ${\geq}457copies/mL$. 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;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Walker RC, Marshall WF, Strickler JG, Wiesner RH, Velosa JA, Habermann TM, et al. Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin Infect Dis 1995;20:1346-53.   DOI
2 Manez R, Breinig MC, Linden P, Wilson J, Torre-Cisneros J, Kusne S, et al. Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease. J Infect Dis 1997; 176:1462-7.   DOI
3 Timms JM, Bell A, Flavell JR, Murray PG, Rickinson AB, Traverse-Glehen A, et al. Target cells of Epstein-Barr-virus (EBV)-positive post-transplant lymphoproliferative disease: similarities to EBV-positive Hodgkin's lymphoma. Lancet 2003;361:217-23.   DOI
4 Dharnidharka VR. Epidemiology of PTLD. In: Dharnidharka VR, Green M, Webber SA, editors. Post-transplant lymphoproliferative disorders. Heidelberg: Springer-Verlag, 2010:17-28.
5 Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, et al. Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study. Lancet 2006;367:233-9.   DOI
6 Wiesmayr S, Webber SA. Heart and lung transplanation. In: Dharnidharka VR, Green M, Webber SA, editors. Post-transplant lymphoproliferative disorders. Heidelberg: Springer-Verlag, 2010:163-72.
7 Green M, Michaels MG, Katz BZ, Burroughs M, Gerber D, Shneider BL, et al. CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients. Am J Transplant 2006; 6:1906-12.   DOI
8 Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y, et al. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant 2005;5:2222-8.   DOI
9 Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transpl Int 2007;20:207-18.   DOI
10 Seo SY, Park SJ, Hwang JY, Hahn SH, Kim SY, Kim HH, et al. The alteration of the positive rate of cytomegalovirus IgG antibody among preschool period children. Korean J Pediatr 2006;49:51-5.   DOI
11 Son KH, Shin MY. Clinical features of Epstein-Barr virusassociated infectious mononucleosis in hospitalized Korean children. Korean J Pediatr 2011;54:409-13.   DOI
12 Swerdlow SH; International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer, 2008.
13 Katz BZ, Pahl E, Crawford SE, Kostyk MC, Rodgers S, Seshadri R, et al. Case-control study of risk factors for the development of post-transplant lymphoproliferative disease in a pediatric heart transplant cohort. Pediatr Transplant 2007;11:58-65.   DOI
14 Hanto DW, Frizzera G, Purtilo DT, Sakamoto K, Sullivan JL, Saemundsen AK, et al. Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res 1981;41(11 Pt 1):4253-61.
15 Frizzera G, Hanto DW, Gajl-Peczalska KJ, Rosai J, McKenna RW, Sibley RK, et al. Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 1981;41(11 Pt 1):4262-79.
16 Luskin MR, Heil DS, Tan KS, Choi S, Stadtmauer EA, Schuster SJ, et al. The impact of EBV status on characteristics and outcomes of posttransplantation lymphoproliferative disorder. Am J Transplant 2015;15:2665-73.   DOI
17 Mynarek M, Schober T, Behrends U, Maecker-Kolhoff B. Posttransplant lymphoproliferative disease after pediatric solid organ transplantation. Clin Dev Immunol 2013;2013: 814973.
18 Cho YU, Chi HS, Jang S, Park SH, Park CJ. Pattern analysis of Epstein-Barr virus viremia and its significance in the evaluation of organ transplant patients suspected of having posttransplant lymphoproliferative disorders. Am J Clin Pathol 2014;141:268-74.   DOI
19 Yancoski J, Danielian S, Ibanez J, Turconi A, Cuarterolo M, Zelazko M, et al. Quantification of Epstein-Barr virus load in Argentinean transplant recipients using real-time PCR. J Clin Virol 2004;31:58-65.   DOI
20 Hayden RT, Hokanson KM, Pounds SB, Bankowski MJ, Belzer SW, Carr J, et al. Multicenter comparison of different real-time PCR assays for quantitative detection of Epstein- Barr virus. J Clin Microbiol 2008;46:157-63.   DOI
21 Preiksaitis JK, Pang XL, Fox JD, Fenton JM, Caliendo AM, Miller GG, et al. Interlaboratory comparison of epstein-barr virus viral load assays. Am J Transplant 2009;9:269-79.   DOI
22 Thorley-Lawson DA, Gross A. Persistence of the Epstein- Barr virus and the origins of associated lymphomas. N Engl J Med 2004;350:1328-37.   DOI
23 Green M, Bueno J, Rowe D, Mazariegos G, Qu L, Abu- Almagd K, et al. Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in children. Transplantation 2000;70:593-6.   DOI