University of Michigan Core Clinical Center for BMT Research Network

描述(申请人提供)：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(TRM)的主要来源。尽管GVHD预防方案取得了进展，但在50-70%的HCT受者中，发生了显著的(II-IV级)急性GVHD，需要大剂量类固醇治疗。这些受者来自于HLA相合的无关供者或部分相合的供者。急性移植物抗宿主病患者的预后仍然很差，需要新的预防策略。密歇根大学的骨髓移植计划为理解GVHD病理生理学和将有希望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，它为该网络的成功做出了关键贡献，包括担任指导委员会主席，担任两项议定书的主席，增加六项议定书的成员资格，并在2007年组织和主办了非常成功的国家科学研讨会。在具体目标I中，本申请提出了在多中心随机第二阶段方案中对两种新的GVHD预防措施(依那西普与Pentostatin/ATG)进行比较，初步数据已由密歇根大学和MD Anderson生成。特殊目的2建议验证四个生物标志物小组(IL2RD、TNFRI、Elafin和Reg3a)从参与拟议试验的患者移植后早期采集的血浆样本中预测GVHD发病的能力。如果得到验证，这个生物标志物小组可以用于后续的骨髓移植CTN试验，以指导急性移植物抗宿主病的预防性治疗。相关性(见说明)：这笔赠款将使密歇根大学成为骨髓移植CTN的核心中心，以便在骨髓移植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.