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Posttransplant Lymphoproliferative Disorder in Pediatric Patients

Characteristics of Disease in EBV-seropositive Recipients

L’Huillier, Arnaud G. MD1,2; Dipchand, Anne I. MD2,3,4; Ng, Vicky L. MD2,3,5; Hebert, Diane MD2,3,6; Avitzur, Yaron MD2,3,5; Solomon, Melinda MD2,3,7; Ngan, Bo-Yee MD2,8; Yeung, Simon BSc1; Stephens, Derek MSc2,9; Punnett, Angela S. MD2,10; Barton, Michelle MD1,3,11; Allen, Upton D. MBBS1,2,3

doi: 10.1097/TP.0000000000002898
Original Clinical Science–General
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Background. Patients at greatest risk of posttransplant lymphoproliferative disorder (PTLD) are those who acquire primary Epstein-Barr virus (EBV) infection after solid organ transplantation. The incidence of PTLD among patients who are EBV-seropositive before transplant is lower, and little is known about the differences in presentation and outcome of this population. We describe the characteristics of EBV-seropositive transplant recipients (R+) who developed PTLD and compare survival outcomes with EBV-seronegative recipients (R−).

Methods. A hospital-based registry was used to identify all patients with biopsy-proven PTLD for the period 2000–2014. Characteristics and outcomes were compared between R+ and R− patients with PTLD.

Results. Sixty-nine patients were included, among which 20 (29.0%) were R+ and 49 (71.0%) were R−. Multiorgan transplant patients accounted for 25% of PTLD cases in R+ patients, while accounting for only 2.1% of all transplants during the study period. There was no difference in PTLD site between R+ and R− patients. PTLD among R+ individuals occurred during the second year after transplant (median: 1.92; range: 0.35–3.09 y) compared with during the first year for R− individuals (median: 0.95; range: 0.48–2.92 y; P = 0.380). There was a trend for a higher overall mortality among R+ individuals (log rank: 0.09). PTLD-related mortality did not differ between R+ and R− individuals (log rank: 0.17).

Conclusions. PTLD among R+ individuals was more likely to occur among multiorgan recipients, and there was a tendency for poorer outcomes at 1 and 5 years after the diagnosis of PTLD.

1 Division of Infectious Diseases, Hospital for Sick Children, Toronto, ON, Canada.

2 University of Toronto, Toronto, ON, Canada.

3 Transplant and Regenerative Medicine Centre, Hospital for Sick Children, Toronto, ON, Canada.

4 Labatt Family Heart Centre, Hospital for Sick Children, Toronto, ON, Canada.

5 Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada.

6 Division of Nephrology, Hospital for Sick Children, Toronto, ON, Canada.

7 Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.

8 Division of Pathology, Hospital for Sick Children, Toronto, ON, Canada.

9 The Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

10 Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.

11 Division of Infectious Diseases, London Health Sciences Centre, University of Western Ontario, London, ON, Canada.

Received 21 March 2019. Revision received 23 June 2019.

Accepted 9 July 2019.

A.G.L. and U.D.A. participated in research design and drafted the manuscript. A.I.D., V.L.N., D.H., Y.A., M.S., S.Y., M.B., and U.D.A. participated in patient enrollment. B.-Y.N. performed the histological analyses. D.S. performed the statistics. S.Y. participated in the performance of the research. All authors participated in the writing and revision of the manuscript and accepted the final version.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

The authors declare no conflicts of interest.

This work was supported by the Division of Infectious Diseases, Hospital for Sick Children.

Correspondence: Upton D. Allen, MBBS, Division of Infectious Diseases, Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada. (upton.allen@sickkids.ca).

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