Pediatric Infection and Vaccine

  • 제24권1호
  • /
  • Pages.44-53
  • /
  • 2017
  • /
  • 2384-1079(pISSN)
  • /
  • 2384-1087(eISSN)
대한소아감염학회 (The Korean Society of Pediatric Infectious Diseases)
권호 표지
DOI QR코드

DOI QR Code

소아 심장이식 후 림프증식성 질환의 진단을 위한 Epstein-Barr Virus 정량 검사의 유용성

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

  • 김준일 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 이진아 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 김영휘 (울산대학교 의과대학 서울아산병원 소아청소년과)
  • 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)
  • 투고 : 2016.09.07
  • 심사 : 2016.10.21
  • 발행 : 2017.04.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목적: 소아 심장이식 환자에서 림프증식성 질환(posttransplant lymphoproliferative disorder [PTLD]) 발생과 Epstein-Barr virus (EBV) 정량값의 상관관계를 분석하고, PTLD의 발생에 영향을 주는 인자들에 대해서 알아보고자 하였다. 방법: 2006년 1월부터 2015년 3월까지 최근 9년간 서울아산병원 어린이병원에서 심장이식을 받은 18세 미만 환자 중 이식 후 최소 1개월 이상 추적 관찰이 가능한 경우를 대상으로 후향적으로 의무기록을 분석하였다. 결과: 총 40명의 심장이식 환자의 진단 시 나이의 중앙값은 11.5세(범위, 0.3-17.8세)였으며 이 중 3명에서 이식 후 4.3개월, 6.3개월 및 17개월째 PTLD가 발생하였다. 이식 후 혈중 EBV 정량 검사를 시행한 28명 중 최소 1회 이상 EBV 바이러스혈증이 관찰된 경우는 7명이었으며, PTLD로 진단받은 환자 3명이 모두 ${\geq}10,000copies/mL$의 EBV 바이러스혈증이 선행되어 있었다. PTLD 발생군은 PTLD 비발생군에 비해 어린 나이에 이식을 받았으며(P=0.021), 초기 및 최고 혈중 EBV 역가가 더 높은 경향을 보였으나 통계적인 차이는 없었다. 결론: 소아 심장이식 환자에서 이식 당시 어린 연령 및 이식 후 EBV 바이러스혈증 동반 여부가 PTLD 발생과 관련이 있었다. 추후 전향적인 연구를 통해서 소아 심장이식 환자에서 PTLD 발생을 적절히 예측할 수 있는 EBV 정량값의 지표를 구하는 것이 필요하겠다.

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.

키워드

참고문헌

  1. 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. https://doi.org/10.1016/S0140-6736(03)12271-4
  2. Dharnidharka VR. Epidemiology of PTLD. In: Dharnidharka VR, Green M, Webber SA, editors. Post-transplant lymphoproliferative disorders. Heidelberg: Springer-Verlag, 2010:17-28.
  3. 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. https://doi.org/10.1016/S0140-6736(06)67933-6
  4. 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.
  5. 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. https://doi.org/10.1111/j.1600-6143.2006.01394.x
  6. 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. https://doi.org/10.1111/j.1600-6143.2005.01002.x
  7. 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. https://doi.org/10.1111/j.1432-2277.2006.00416.x
  8. 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. https://doi.org/10.3345/kjp.2006.49.1.51
  9. Son KH, Shin MY. Clinical features of Epstein-Barr virusassociated infectious mononucleosis in hospitalized Korean children. Korean J Pediatr 2011;54:409-13. https://doi.org/10.3345/kjp.2011.54.10.409
  10. 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.
  11. 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. https://doi.org/10.1111/j.1399-3046.2006.00609.x
  12. 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.
  13. 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.
  14. 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. https://doi.org/10.1111/ajt.13324
  15. Mynarek M, Schober T, Behrends U, Maecker-Kolhoff B. Posttransplant lymphoproliferative disease after pediatric solid organ transplantation. Clin Dev Immunol 2013;2013: 814973.
  16. 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. https://doi.org/10.1309/AJCP9WYEXKOL9YUV
  17. 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. https://doi.org/10.1016/j.jcv.2004.02.015
  18. 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. https://doi.org/10.1128/JCM.01252-07
  19. 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. https://doi.org/10.1111/j.1600-6143.2008.02514.x
  20. 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. https://doi.org/10.1056/NEJMra032015
  21. 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. https://doi.org/10.1097/00007890-200008270-00010
  22. 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. https://doi.org/10.1093/clinids/20.5.1346
  23. 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. https://doi.org/10.1086/514142

피인용 문헌

  1. Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia vol.34, pp.30, 2019, https://doi.org/10.3346/jkms.2019.34.e203
  2. Epstein‐Barr viral load monitoring for diagnosing post‐transplant lymphoproliferative disorder in pediatric liver transplant recipients vol.24, pp.4, 2017, https://doi.org/10.1111/petr.13666