Optimizing Outcome After Pediatric Heart Transplantation

描述(由申请人提供)： 在过去的15年里，患者的预后有了显著的改善，以至于心脏移植现在被认为是一种公认的治疗方法，短期内成功的可能性很高。然而，给患者和家属带来的情感、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被移植的儿童预计不会活到成年。免疫抑制方案具有许多固有的风险，包括感染、恶性肿瘤和多器官毒性。此外，这些药物对慢性排斥反应的发展几乎没有影响，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建议的中心范式是，儿科心脏移植后临床结果的进一步改善取决于将基础科学进步与临床方案中证据驱动的修改联系起来的新策略。SCCOR的这项建议将汇聚儿科心脏病学(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，以推进开发管理儿科心脏移植受者的新方法的共同目标。我们的长远目标是： 1.制定长期接受移植物而不需要免疫抑制的策略。 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.确定可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.开发用于排异监测的非侵入性诊断策略，以降低成本，提高质量和生命长度。 这项儿科CV SCCOR建议通过新颖的、假设驱动的项目解决了这些领域中的每一个领域，以迅速和显著地促进儿科心脏移植接受者的最先进护理。

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.