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）已被证明是有效的治疗方法，甚至是治疗影响淋巴造血系统的各种恶性和非恶性疾病的首选。重大进展，特别是在支持性护理领域，减少了骨髓移植的并发症，使其可以应用于老年患者和严重的，但非致命的疾病。较新的抗生素方案和造血生长因子显著减少了感染并发症。患者的选择、治疗监测和低强度的降低强度预处理方案可以显著降低方案相关的毒性，如肝静脉闭塞性疾病。我们的项目重点关注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证明，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赠款资助的转化临床研究发现，BMT后高剂量Cy有效调节同种异体反应性（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人在试点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来测试似乎有希望的临床方法。因此，一个能够快速有效地进行BMT多中心试验的正式临床网络至关重要，特别是随着有前途的新疗法的持续快速发展。因此，我们的结果与单倍体相关的BMT已证实在最近完成的BMT临床试验网络（CTN）试验（BMT CTN 0603）。BMT CTN试验不仅证明了这种方法的有效性，而且可以安全地出口。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）提出在网络中实施的临床试验：一项随机、III期试验，非清髓性脐带血移植与非清髓性单倍体相合BMT。相关性（见说明）：我们的小组和其他人在BMT患者的新临床方法试点方面取得了巨大成功。然而，一个单一的机构很难进行确定性的试验，测试有前途的新的临床。因此，一个正式的临床网络，可以快速，有效地进行多中心试验的BMT是至关重要的。

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.