Papaz Tanya, Allen Upton, Blydt-Hansen Tom, Birk Patricia E, Min Sandar, Hamiwka Lorraine, Phan Veronique, Schechter Tal, Wall Donna A, Urschel Simon, Foster Bethany J, Mital Seema
Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Canadian National Transplant Research Program, Edmonton, Alberta, Canada.
Transplant Direct. 2018 Nov 27;4(12):e410. doi: 10.1097/TXD.0000000000000842. eCollection 2018 Dec.
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.
尽管在生物学、生理学和行为方面存在与年龄相关的差异，但移植免疫抑制并未根据年龄进行调整。这可能导致高移植失败率和移植后并发症。我们介绍了“移植儿科结局：个性化免疫抑制以提高疗效研究”的目标、设计和方法，该研究旨在使儿童和年轻成人的移植后免疫抑制个性化。
在这项前瞻性观察性队列研究中，我们从加拿大各地的14个移植中心招募了儿科和年轻成人实体器官移植受者、儿科异基因造血干细胞移植受者以及匹配的活体和已故器官捐赠者。在多个时间点收集临床数据、问卷、生物标本和药房记录：（1）识别影响不同年龄和移植类型免疫抑制剂量需求的遗传和宿主免疫因素，（2）识别增加对爱泼斯坦-巴尔病毒感染易感性的病毒-宿主相互作用，（3）确定与青少年和年轻成人药物依从性相关的护理过程和结构。
2015年至2018年，对1662名新的和现有的移植受者进行了筛查，1166名因各种目标被招募，包括370例肝移植、445例肾移植、277例心脏移植、19例肺移植、19例多器官移植和36例造血干细胞移植。入组时，12%的患者年龄小于2岁，30%为2至10岁，42%为10至18岁，16%为18至24岁。931人同意参与目标1和2（同意率90%），287人同意参与目标3（同意率82%）。收集的生物标本包括898份用于DNA检测、276份用于免疫测定、717份用于生物标志物研究。70%的参与者已完成随访；30%的参与者等待研究完成。
这个全国性多中心跨器官网络的设计有助于最大限度地招募大量患者队列，以研究免疫抑制需求方面与年龄和器官相关的差异，否则这是不可行的。利用该队列独特的临床、生物学、环境和行为特征将有助于制定个性化移植后免疫抑制的精准医学策略。
