Blood and Marrow Transplant Clinical Trials Network

描述(申请人提供)：杜克大学医学中心的儿科和成人移植项目自2001年成立以来一直是BMT-CTN的核心临床中心。作为一个核心中心，杜克大学为该网络做出了重大贡献，包括招募了117名使用CTN方案的患者，主持了两个方案(Kurtzberg博士主持0501和Horwitz博士主持0901)；在6个方案委员会和2个疾病委员会任职，撰写手稿，建立和管理方案0501的免疫重建核心。该中心一直在遵守准确和及时的数据和生物标本提交。国际和平倡议和共同国际定期出席指导委员会会议和电话会议。杜克大学为CTN带来了两类专业知识：(1)在脐带血移植和银行方面的长期和开拓性作用；(2)在治疗非恶性疾病的造血干细胞移植儿科患者方面的独特经验。本申请中提出的研究概念，基于杜克大学正在进行的工作，将作为BMT-CTN 0501后续研究的基础。它的重点是促进对UCBT后植入的机制的理解。通过对库存(来自卡罗莱纳州脐带血库)和杜克大学移植结果的分析，我们已经表明，在解冻的脐带血单位中加入集落形成单位(CFU)与植入最相关。进一步分析冷冻保存前和解冻后脐血单位的其他参数，使我们开发出一种预测性评分系统，被称为“脐血APGAR”(CBA)，在回顾验证中，该系统最准确地确定脐血效力，并与植入潜力最密切相关。我们建议测试和前瞻性地验证CBA以优化UCBT患者的CBU选择。这项工作的首要目标是减少植入延迟和UCBT后初次移植物失败率，增加UCBT的总体成功率。相关性(参见说明)：BMT-CTN是一个非常重要的移植中心网络，它共同努力，为接受移植治疗的恶性和非恶性疾病患者确定最佳实践和最佳治疗方法。杜克大学自2001年以来参加了CTN，并为其使命做出了重大贡献。这一应用的研究建议将提高脐带血移植的安全性和有效性。

DESCRIPTION (provided by applicant): The pediatric and adult transplant programs at Duke University Medical Center have served as a core clinical center for the BMT-CTN since its establishment in 2001. As a core center, Duke has made significant contributions to the network, including enrollment of 117 patients on CTN protocols, chairing two protocols (Dr. Kurtzberg chairs 0501 and Dr. Horwitz chairs 0901); serving on 6 protocol committees and 2 disease committees, authoring manuscripts and establishing and managing the immune reconstitution core for protocol 0501. The center has been in compliance with accurate and timely data and bio-specimen submission. The PI and Co-PI have regularly attended steering committee meetings and conference calls. Duke brings two specialized types of expertise to the CTN, (1) a long-standing and pioneering role in cord blood transplantation and banking and (2) unique experience in the treatment of pediatric patients with hematopoietic stem cell transplantation for non-malignant diseases. The study concept proposed in this application, based on ongoing work at Duke, will serve as the foundation for a follow-on study to BMT-CTN 0501. It is focused on furthering the understanding of the mechanisms that underlie engraftment after UCBT. Through analyses of banking (from the Carolinas Cord Blood Bank) and transplant outcomes at Duke, we have shown that dosing of colony forming units (CFUs) in thawed cord blood units best correlates with engraftment. Further analyses of additional parameters characterizing cord blood units before cryopreservation and after thawing allowed us to develop a predictive scoring system, coined the "cord blood apgar" (CBA) which, in a retrospective validation, most accurately determines cord blood potency and most closely correlates with engraftment potential. We propose to test and prospectively validate the CBA to optimize CBU selection in patients undergoing UCBT. The overarching goal of this work is to reduce engraftment delays and rates of primary graft failure after UCBT, increasing the overall success of UCBT. RELEVANCE (See instructions): The BMT-CTN is a highly important network of transplant centers working together to identify best practices and best therapies for patients with malignant and non-malignant diseases treated with transplantation. Duke has participated in the CTN since 2001 and has contributed significantly to its mission. The research proposal in this application will increase safety and efficacy of cord blood transplantation.