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Elevated Risk of Cancer After Solid Organ Transplant in Childhood

A Population-based Cohort Study

Kitchlu, Abhijat, MD1; Dixon, Stephanie, PhD2,3; Dirk, Jade S.2; Chanchlani, Rahul, MD1,4; Vasilevska-Ristovska, Jovanka, MD4; Borges, Karlota4; Dipchand, Anne I., MD5,6; Ng, Vicky L., MD7; Hebert, Diane, MD1,4; Solomon, Melinda, MD7; Michael Paterson, J.2,8; Gupta, Sumit, MD, PhD2,9; Joseph Kim, S., MD, PhD1,2,8; Nathan, Paul C., MD2,4; Parekh, Rulan S., MD, FRCPC1,4,7

doi: 10.1097/TP.0000000000002378
Original Clinical Science—General
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Background. Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients.

Methods. We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto, from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death.

Results. A total of 951 recipients (kidney, n = 400; liver, n = 283; heart, n = 218; lung, n = 36; multiorgan/small bowel, n = 14) were compared with 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio, 32.9; 95% confidence interval [CI], 26.6–40.8). Risk was highest in the first year posttransplant (adjusted hazard ratio [aHR],176; 95% CI, 117–264), but remained elevated beyond 10 years (aHR, 10.8; 95% CI, 6.3–18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR, 93.1; 95% CI, 59.6–145.2).

Conclusions. Childhood transplant recipients have a 30 times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population.

1Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.

2Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

3Department of Epidemiology and Biostatistics, Western University, Toronto, Ontario, Canada.

4Division of Nephrology, Hospital for Sick Children, Toronto, Ontario, Canada.

5Labatt Family Heart Centre, Hospital for Sick Children, Toronto, Ontario, Canada.

6Division of Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.

7Transplant and Regenerative Medicine Centre, Hospital for Sick Children, Toronto, Ontario, Canada.

8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.

9Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.

Received 7 January 2018. Revision received 6 July 2018.

Accepted 11 July 2018.

R.S.P. received funding from the Transplant & Regenerative Medicine Centre (TRMC) Catalyst Grant at The Hospital for Sick Children, Ashley’s Angels Catwalk and the Canadian Institutes of Health Research (CIHR) for the completion of this study.

The authors declare no conflicts of interest.

A.K., S.D., S.J.K., P.C.N., and R.S.P participated in the study design. A.K., S.D., S.G., and P.C.N. participated in the data analysis. A.K., S.D., J.S.D., P.C.N., and R.S.P drafted the article. All authors read and approved the final article.

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).

Correspondence: Rulan S. Parekh, MD, FRCPC, The Hospital for Sick Children (SickKids), 686 Bay Street, Child Health Evaluative Sciences, 11th floor, Toronto, ON, Canada M5G 0A4. (rulan.parekh@sickkids.ca).

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