Improving the Outcomes of Stem Cell Transplantation

造血干细胞移植是一种治疗多种血液病的有效方法， 免疫、代谢和恶性疾病。这是一个高风险的程序，可能会因以下原因而复杂化 移植物对宿主疾病、移植物排斥反应、与方案相关的毒性和感染并发症。 需要改进治疗策略以改善结果并减少毒副作用。 移植物抗宿主病是限制造血的广泛应用的主要并发症。 需要移植和新的、更有效的治疗方法。具体目标：我们提出了第二阶段 随机多中心试验比较标准GVIHD预防与依那西普与 无血缘关系的供者血细胞集落刺激因子中的五肽抑素/ATG。这是一项多中心前瞻性研究，旨在检查两项 预防移植物抗宿主病的有希望的方法，从L/11的一项大阶段研究中衍生出五肽他汀臂 在我们的中心(Parmar等人，2010)和etanercept ARM与加州大学的合作者一起开发 密歇根州。拟议的研究将检验这样一种假设，即将依那西普或Pentostatin/ATG添加到 标准的GVHD预防措施将提高接受匹配无关治疗的患者的6个月NRM率 血细胞移植治疗恶性血液病与CIBMTR历史比率的比较 GVHD预防护理标准数据库。此试验的主要终点将是6点的NRM 移植后几个月。次要终点是指从移植时起两年的存活率， 中性粒细胞和血小板植入，移植物衰竭，急性移植物抗宿主病(GVHD)，慢性GVHD， 目前的免疫抑制无存活、复发、感染和不良事件。生物相关性将是 评估对移植物抗宿主病的发展和预后的预测。目标是找出最有希望的 在未来的第三阶段研究中进行进一步最终测试的方案。 该申请是德克萨斯大学-MD安德森癌症中心的竞争性续签 (MDACC)作为血液和骨髓移植的核心临床中心-临床试验网络。MDACC是 全国最大的NCI指定的综合癌症中心，临床和翻译领域的领先者 造血移植方面的研究。我们致力于BMT-CTN的成功并继续 成为组织中的领导者。我们是BMT-CTN研究和发展的主要贡献者 积极鼓励患者参与其研究。

Hematopoietic stem cell transplantation is an effective treatment for a broad range of hematologic, immune, metabolic and malignant diseases. This Is a high-risk procedure which may be complicated by graft-vs.-host disease, graft rejection, regimen related toxicities and infectious complications. Improved therapeutic strategies are needed to improve the outcome and reduce the toxicities. Graft-vs.-host disease is the major complication limiting the broader application of hematopoietic transplantation and novel, more effective therapy is needed. Specific Aim: We propose a Phase II Randomized, Multicenter Trial Comparing Standard GVIHD Prophylaxis with Etanercept vs. Pentostatin/ATG in Unrelated Donor HCT. This is a multicenter prospective study to examine two promising approaches for prevention of GVHD, with the pentostatin arm derived from a large phase l/ll study at our center(Parmar, et al 2010) and the etanercept arm developed with collaborators at the University of Michigan. The proposed study will test the hypothesis that the addition of etanercept or pentostatin/ATG to standard GVHD prophylaxis will improve 6-month NRM rates for patients undergoing matched unrelated HCT for the treatment of hematologic malignancies when compared to historical rates from the CIBMTR database with standard of care GVHD prophylaxis. The primary endpoint for this trial will be NRM at 6 months post-transplant. Secondary endpoints are two-year survival from the time of transplant, incidences of neutrophil and platelet engraftment, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, current immunosuppressive free survival, relapse, infections, and adverse events. Biologic correlates will be assessed to predict development of GVHD and its prognosis. The goal is to identify the most promising regimen for further definitive testing in a future Phase III study. The application is a competitive renewal of the University of Texas- MD Anderson Cancer Center (MDACC) as a Core Clinical Center for Blood and Marrow Transplant-Clinical Trials Network. MDACC is the nation's largest NCI designated Comprehensive Cancer Center, and a leader in clinical and translational research in hematopoietic transplantation. We are committed to the success of the BMT-CTN and continue to be leaders in the organization. We are a major contributor to the development of BMT-CTN studies and active accrue patients to its studies.