Despite age-related differences in biology, physiology, and behavior, transplant immunosuppression is not tailored by age. This likely contributes to high graft failure and posttransplant complications. We present the aims, design, and methods of the Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy Study aimed at personalizing posttransplant immunosuppression in children and young adults.
In this prospective observational cohort study, we recruited pediatric and young adult solid organ transplant, pediatric allogeneic hematopoietic stem cell transplant recipients, and matched living and deceased organ donors from 14 transplant centers across Canada. Clinical data, questionnaires, biospecimens, and pharmacy records were collected at serial time points: (1) to identify genetic and host immune factors that influence immunosuppression dose requirements across different ages and transplant types, (2) to identify viral-host interactions that increase susceptibility to Epstein-Barr virus infection, and (3) to define care processes and structures associated with medication adherence in adolescents and young adults.
From 2015 to 2018, 1662 new and prevalent transplant recipients were screened, 1166 were recruited for the various aims, including 370 liver, 445 kidney, 277 heart, 19 lung, 19 multiple, and 36 hematopoietic stem cell transplant transplants. Twelve percent were younger than 2 years, 30% were 2 to 10 years, 42% were 10 to 18 years, and 16% were 18 to 24 years at enrollment. Nine hundred thirty-one consented to participation in aims 1 and 2 (90% consent rate), 287 to aim 3 (82% consent rate). Biospecimens collected included 898 for DNA, 276 for immunoassays, and 717 for biomarker studies. Seventy percent participants have completed follow-up; 30% are pending study completion.
The design of this national multicenter cross-organ network helped maximize recruitment of a large patient cohort for studying age and organ-related differences in immunosuppression needs that would not otherwise be feasible. Leveraging the unique clinical, biological, environmental, and behavioral characteristics of this cohort will help develop precision medicine strategies for individualizing posttransplant immunosuppression.
1 Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
2 Canadian National Transplant Research Program, Edmonton, Alberta, Canada.
3 Division of Infectious Diseases, Hospital for Sick Children, Toronto, Ontario, Canada.
4 Division of Pediatric Nephrology, University of British Columbia, Vancouver, Canada.
5 Department of Pediatrics and Child Health, Health Sciences Centre Winnipeg, Winnipeg, Manitoba, Canada.
6 Division of Nephrology, Alberta Children's Hospital, University of Calgary, Calgary, Canada.
7 Division of Nephrology, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
8 Division of Hematology Oncology and Bone Marrow Transplantation, Hospital for Sick Children, Toronto, Ontario, Canada.
9 Division of Pediatric Cardiology, University of Alberta, Edmonton, Alberta, Canada.
10 Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Published online 27 November, 2018.
Received 22 August 2018. Revision requested 18 June 2018.
Accepted 15 September 2018.
The authors declare no conflicts of interest.
This work is part of the Canadian National Transplant Research Program (CNTRP) and was supported by the Canadian Institutes for Health Research (CIHR) and partners (grant TFU 127880). Support was also provided by Astellas Pharma Canada, Inc.
S.M., B.J.F., U.A., and S.U. are study investigator scientific leads who have contributed to the research design, analysis and interpretation of data for the project. Study investigators, T.B.-H., V.P., P.E.B, L.H., T.S., and D.A.W., have contributed to the design of the work. T.P. and S.Min. contributed toward data acquisition and analysis. The article was drafted by T.P. and S.M. All authors have approved of the final version to be published.
Trial Registration: ClinicalTrials.gov registration NCT02318030. Registered November 25, 2014.
Correspondence: Seema Mital, MD, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. (firstname.lastname@example.org).
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