Translational Research in Blood and Marrow Translplantation

描述（由申请人提供）：在过去的四十年中，血液和骨髓移植（BMT）已被证明是一种有效的治疗方法，甚至是治疗多种影响淋巴造血系统的恶性和非恶性疾病的首选。特别是在支持性护理领域的重大进展减少了BMT的并发症，因此可以将其应用于老年患者和严重但非致命的疾病。较新的抗生素治疗方案和造血生长因子显著减少了感染并发症。患者选择、治疗监测和较低强度的低强度调理方案大大降低了方案相关的毒性，如肝脏静脉闭塞性疾病。我们的项目专注于移植生物学从实验室到临床的转化。新的临床前和临床数据已经表明，新开发的方法将改善BMT的结果，并增加其适应症。我们机构的BMT研究的基础是两个正在进行的项目，研究移植生物学的各个方面。我们在过去十年中由这些资助资助的转化临床研究发现，高剂量Cy在BMT后有效调节同种异体反应（GVHD和移植物排斥），允许安全有效的单倍体相关BMT。然而，尽管我们的团队和其他团队在试验新的临床方法方面取得了巨大的成功，但单个项目很难进行明确的试验，以测试看起来有希望的临床方法。因此，一个能够快速有效地开展BMT多中心试验的正式临床网络至关重要，尤其是在有前景的新疗法不断快速发展的情况下。因此，我们的结果与单倍体相关的BMT已在最近完成的BMT临床试验网络（CTN）试验（BMT CTN 0603）中得到证实。BMT CTN试验不仅证明了这种方法的有效性，而且还证明了它可以安全地输出。我们作为核心临床中心的具体目标是：1)通过BMT CTN参与多中心试验，2)提出一项临床试验在网络中实施：一项随机的III期试验，非清髓脐带血移植与非清髓单倍同体BMT。相关性（见说明）：我们的团队和其他团队在为BMT患者试验新的临床方法方面取得了巨大成功。然而，单一机构很难开展有前途的新临床试验。因此，一个能够快速有效地开展BMT多中心试验的正式临床网络至关重要。

DESCRIPTION (provided by applicant): Over the past four decades, blood and marrow transplantation (BMT) has proven to be effective therapy, and even the treatment of choice, for a variety of malignant and nonmalignant diseases that affect the lymphohematopoietic system. Major advances, particularly in the area of supportive care, have decreased the complications of BMT, so that it can be applied to older patients and to severe, but non-fatal, diseases. Newer antibiotic regimens and hematopoietic growth factors have significantly reduced infectious complications. Patient selection, therapeutic monitoring, and less intensive reduced intensity conditioning regimens have substantially decreased regimen-related toxicities such as veno-occlusive disease ofthe liver. Our program has focused on the translation of transplantation biology from the laboratory to the clinic. New preclinical and clinical data already demonstrate that newly developing approaches will improve the outcome of BMT, as well as increase its indications. The foundation of our institution's BMT research has been two ongoing Program Projects that study various aspects of transplantation biology. Our translational clinical studies funded by these grants over the past decade have found that high-dose Cy post BMT effectively modulated alloreactivity (GVHD and graft rejection), allowing safe and effective haploidentical related BMT. However, although our group and others have had great success in piloting novel clinical approaches, it is difficult for a single program to carry out definitive trials that test clinical approaches that appear promising. Thus, a formal clinical network that can rapidly and efficiently conduct multi-center trials in BMT is critically important, especially with the ongoing rapid development of promising new therapies. Accordingly, our results with haploidentical related BMT have been confirmed in a recently completed BMT Clinical Trials Network (CTN) trial (BMT CTN 0603). Not only did the BMT CTN trial demonstrate the effectiveness of this approach, but also that it can be safely exported. Our specific aims as a Core Clinical Center are: 1) participate in multi-center trials through the BMT CTN, and 2) propose a clinical trial for implementation in the Network: a randomized, phase III trial non-myeloablative umbilical cord blood transplantation versus non-myeloablative haploidentical BMT. RELEVANCE (See instructions): Our group and others have had great success in piloting new clinical approaches for BMT patients. However, it is difficult for a single institution to carry out definitive trials that test promising new clinical. Thus, a formal clinical network that can rapidly and efficiently conduct multi-center trials in BMT is critically important.