Translational Research in Blood and Marrow Translplantation

描述(申请人提供)：在过去的40年里，血液和骨髓移植(BMT)已被证明是一种有效的治疗方法，甚至是影响淋巴造血系统的各种恶性和非恶性疾病的首选治疗方法。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，因此它可以应用于老年患者和严重但非致命的疾病。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、治疗监测和强度较小的低强度预适应方案大大减少了与方案相关的毒性，如肝静脉闭塞疾病。我们的项目重点是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骨髓移植的结果，并增加其适应证。我们机构的骨髓移植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翻译性临床研究发现，BMT后大剂量Cy有效地调节了同种异体反应性(GVHD和移植物排斥反应)，允许安全有效的半相合相关BMT。然而，尽管我们的团队和其他人在试验新的临床方法方面取得了巨大的成功，但对于一个单一的计划来说，很难进行决定性的试验，以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骨髓移植多中心试验的正式临床网络至关重要，特别是在前景看好的新疗法正在快速发展的情况下。因此，我们的半相合相关骨髓移植的结果在最近完成的骨髓移植临床试验网络(CTN)试验(BMT CTN 0603)中得到了证实。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出口。我们作为核心临床中心的具体目标是：1)通过骨髓移植CTN参与多中心试验，2)建议在该网络中实施一项临床试验：非清髓性脐血移植与非清髓性半相合骨髓移植的随机III期试验。相关性(参见说明书)：我们团队和其他人在为骨髓移植患者试验新的临床方法方面取得了巨大成功。然而，对于一家机构来说，很难进行最终的试验，测试有希望的新临床。因此，一个能够快速有效地进行骨髓移植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.