University of Michigan Core Clinical Center for BMT Research Network

描述（由申请方提供）：急性移植物抗宿主病（GHVD）仍然是异基因造血干细胞移植（HCT）后发病率和移植相关死亡率（TRM）的主要来源。尽管在GVHD预防方案方面取得了进展，但在来自HLA匹配的无关供体或部分HLA匹配的供体的移植物的50-70%的HCT接受者中发生需要用高剂量类固醇全身治疗的显著（II-IV级）急性GVHD。急性GVHD患者的结局仍然很差，需要新的预防策略。密歇根大学的BMT项目为GVHD病理生理学的理解和将有前途的新方法转化为临床试验做出了开创性的贡献。密歇根大学在十年前成立时被选为BMT CTN的创始成员，并为网络的成功做出了关键贡献，包括指导委员会主席，两个协议的主席，六个协议的额外成员，以及组织和主办2007年非常成功的科学研讨会。本申请在具体目的I中提出了在多中心、随机II期方案中比较两种新的GVHD松弛所需的药物（依那西普vs喷司他丁/ATG），其初步数据已在密歇根大学和MD安德森获得。具体目标2提出验证四种生物标志物组（IL 2 Rd、TNFRI、Elafin和Reg 3a），其能够从参与拟议试验的患者移植后早期采集的血浆样本预测GVHD的发作。如果得到验证，该生物标志物组可用于随后的BMT CTN试验，以指导急性GVHD的抢先治疗。相关性（参见说明）：这笔赠款将使密歇根大学成为BMT CTN的核心中心，以便在BMT患者中进行多中心临床试验。

DESCRIPTION (provided by applicant): Acute graft versus host disease (GHVD) remains a major source of morbidity and transplant-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). Despite advances in GVHD prophylactic regimen, significant (grade II-IV) acute GVHD that requires systemic treatment with high dose steroids occurs in 50-70% of HCT recipients of transplants from HLA-matched unrelated donor or partially HLA-matched donors. Outcomes for patients developing acute GVHD remain poor and new prophylactic strategies are needed. The University of Michigan BMT program has made seminal contributions to the understanding of GVHD pathophysiology and to the translation of promising new approaches into clinical trials. The University of Michigan was chosen to be a charter member of the BMT CTN at its inception ten years ago, and it has made key contributions to the success of the network, including a chairmanship of the steering committee, chairmanships of two protocols, additional memberships in six protocols, and the organization and hosting of the highly successful State of the Science Symposium in 2007. This application proposes, in specific Aim I, the comparison of two novel GVHD prophylaxis-required (etanercept vs pentostatin/ATG) in a multicenter, randomized Phase II protocol, the preliminary data for which having been generated at the University of Michigan and MD Anderson. Specific Aim 2 proposes to validate a four biomarker panel (IL2Rd, TNFRI, Elafin and Reg3a) for its ability to predict the onset of GVHD from plasma samples taken early after transplant from patients participating in the proposed trial. If validated, this biomarker panel could be used in subsequent BMT CTN trials to guide the preemptive treatment of acute GVHD. RELEVANCE (See instructions): This grant will make the University of Michigan a Core Center for the BMT CTN in order to conduct multi- center clinical trials in BMT patients.