Blood and Marrow Transplant Clinical Trials Network

描述（由申请人提供）：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。作为核心中心，杜克大学为CTN网络做出了重大贡献，包括招募117名患者参与CTN协议，主持两个协议（Kurtzberg博士主持0501，Horwitz博士主持0901）；在6个方案委员会和2个疾病委员会任职，为0501方案撰写稿件并建立和管理免疫重建核心。本中心一直遵守准确、及时的数据和生物标本提交。PI和联合PI定期参加指导委员会会议和电话会议。杜克大学为CTN带来了两种专门的专业知识，(1)在脐带血移植和储存方面的长期开创性作用，(2)在治疗非恶性疾病的儿科患者造血干细胞移植方面的独特经验。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。它的重点是进一步了解UCBT后植入的机制。通过对银行（来自卡罗莱纳脐带血银行）和杜克大学移植结果的分析，我们已经表明，在解冻脐带血单位中菌落形成单位（cfu）的剂量与移植最相关。进一步分析冷冻保存前和解冻后脐带血单位的其他参数，使我们能够开发一种预测评分系统，创造了“脐带血apgar”（CBA），在回顾性验证中，该系统最准确地确定了脐带血的效力，并与植入潜力密切相关。我们建议对CBA进行测试和前瞻性验证，以优化接受UCBT患者的CBU选择。这项工作的总体目标是减少UCBT后移植延迟和原发性移植失败率，提高UCBT的整体成功率。相关性（见说明）：BMT-CTN是一个非常重要的移植中心网络，共同为接受移植治疗的恶性和非恶性疾病患者确定最佳做法和最佳疗法。杜克大学自2001年以来一直参与CTN，并为其使命做出了重大贡献。本研究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.