Optimizing Outcome After Pediatric Heart Transplantation

描述（由申请人提供）： 在过去的15年中，患者的预后发生了显着改善，因此心脏移植现在被认为是一种短期成功可能性很高的既定疗法。然而，患者和家庭的情感，经济，社会和医疗负担仍然巨大，心脏移植治疗仍然是姑息性的。事实上，大多数在婴儿期和儿童期接受移植的儿童预计无法存活到成年。免疫抑制方案具有许多固有风险，包括感染、恶性肿瘤和多个终末器官毒性。此外，这些药物对慢性排斥反应的发展几乎没有影响，而慢性排斥反应是移植后晚期死亡的主要原因。推动这一综合SCCOR提案的中心范式是，儿科心脏移植后临床结局的进一步改善取决于将基础科学进展与临床方案中的循证驱动修改联系起来的新策略。该SCCOR提案将汇集儿科心脏病学（心脏移植）和心脏外科、免疫学、传染病、分子遗传学和生物统计学领域的专家，以推进开发儿科心脏移植受者管理新方法的共同目标。我们的长期目标是： 1.制定无需免疫抑制即可实现长期移植物接受的策略。 2.制定策略以减少与非特异性免疫抑制方案相关的发病率。 3.确定预测移植后儿童移植结果差异的遗传标记，包括种族差异。 4.开发用于排斥监测的非侵入性诊断策略，以降低成本，提高质量和寿命。 本儿科CV SCCOR提案通过新颖的假设驱动项目解决了这些领域中的每一个问题，以快速显著地推进儿科心脏移植受者的最先进护理。

DESCRIPTION (provided by applicant): Over the last 15 years, significant improvements in patient outcome have occurred such that heart transplantation is now considered an established therapy with a high likelihood for short-term success. However, the emotional, financial, social and medical burdens placed on patients and families remain enormous and heart transplantation therapy remains palliative. Indeed, most children transplanted in infancy and childhood are not predicted to survive to adulthood. The immunosuppressive regimens have many inherent risks including infections, malignancy and multiple end-organ toxicities. Furthermore, these agents have had little impact on the development of chronic rejection, the leading cause of death late after transplantation. The central paradigm driving this integrated SCCOR proposal is that further improvements in clinical outcome following pediatric heart transplantation depend upon novel strategies that link basic science advances with evidence-driven modifications in clinical protocols. This SCCOR proposal will bring together experts in the fields of pediatric cardiology (cardiac transplantation) and cardiac surgery, immunology, infectious disease, molecular genetics, and biostatistics to advance the common goal of developing novel approaches to the management of pediatric heart transplant recipients. Our long-term goals are to: 1. Develop strategies that result in long-term graft acceptance without requiring immunosuppression. 2. Develop strategies to reduce the morbidities related to non-specific immunosuppressive protocols. 3. Identify genetic markers that predict disparities in transplant outcomes in children after transplantation, including racial disparities. 4. Develop non-invasive diagnostic strategies for rejection surveillance that reduce cost and improve quality and length of life. This Pediatric CV SCCOR proposal addresses each of these areas with novel, hypothesis driven projects to rapidly and significantly advance the state-of-the-art care for pediatric heart transplant recipients.