The Ohio State University Blood and Marrow Transplant Research Consortium

项目摘要 虽然hct为患有各种良性和恶性疾病的患者提供了潜在的治疗方法，但两者 急性和慢性移植物抗宿主病(GVHD)继续困扰着这一领域，并经常限制患者的寿命和 我们患者的生活质量。而骨髓(BM)或动员外周血(MPB)是合适的 供者来源的造血细胞，这种网络建立在BMT CTN 0201上的那个粒细胞集落 刺激因子(G-CSF)MPB与慢性移植物抗宿主病(CGVHD)的高风险和较差的 与骨髓相比，无血缘关系的供者血细胞移植后的生命。类似的结果在接受治疗的人身上也得到了证实 来自匹配的兄弟姐妹的MPB。俄亥俄州血液和骨髓移植研究联盟(OSUBMT- RC)由五个经验丰富的移植中心组成，它们在生产力方面有着良好的记录 进行临床试验。我们的联盟提出了一种新的方法来限制HCT后的GVHD，方法是 建立用于移植的供者造血细胞采购的新标准。OSUBMT- RC Pi开创了一种使用CXCR4拮抗剂plerixafor获取HCT供体细胞的新方法 没有G-CSF。Plerixafor动员CD34细胞和其他免疫细胞进行移植的速度比 G-CSF(1vs5d)，对供者毒性较小。单用plerixafor(P-MPB)后获得的移植物促进 完全植入和基于最近由PI领导的多中心II期研究，似乎重建了免疫 比G-MPB更快，可能导致较少的慢性移植物抗宿主病(CGVHD)。这些优势似乎特别突出 在接受强度降低的同种异体移植的老年患者中令人震惊。根据这些数据，我们假设P-MPB 将成为购买MPB用于HCT的合适且可能更可取的替代方法，因为 对供者来说更方便、毒性更小，GVHD更少，免疫力更好 受者的重建。我们建议通过以下具体目标来检验这些假设： 目的1：我们将在匹配的受者中进行P-MPB和G-MPB的随机II期研究 以无cGVHD、无复发存活率为主要终点的同胞同种异体移植。 目的2：我们将检验P-MPB与G-MPB促进免疫重建的假设 通过T、B、NK和树突状细胞的相关表型、功能和基因序列研究 从同种异体移植受者体内获取的细胞 拟议的研究涉及2014年缔约国设立的BMT CTN的几个关键优先事项 科学研讨会，如果有希望的话，将为未来最终的第三阶段试验铺平道路，这可能会从根本上 改进我们从捐赠者那里收集同种异体移植的程序。

Project Summary While HCT offers potentially curative therapy to patients with a variety of benign and malignant diseases, both acute and chronic graft versus host disease (GVHD) continue to plague the field and often limit the longevity and quality of life of our patients. While either bone marrow (BM) or mobilized peripheral blood (MPB) are suitable sources of donor hematopoietic cells, this network established in BMT CTN 0201 that granulocyte colony stimulating factor (G-CSF) MPB is associated with a higher risk of chronic GVHD (cGVHD) and worse quality of life following unrelated donor HCT compared to BM. Similar results have been demonstrated in recipients of MPB from matched siblings. The Ohio State Blood and Marrow Transplant Research Consortium (OSUBMT- RC) is comprised of five highly experienced transplant centers with a well-established track record of productivity conducting clinical trials. Our consortium proposes a novel approach to limiting GVHD following HCT by establishing a new standard for the procurement of donor hematopoietic cells for transplantation. The OSUBMT- RC PI has pioneered a novel method to procure donor cells for HCT using the CXCR4 antagonist plerixafor without G-CSF. Plerixafor mobilizes CD34+ cells and other immune cells for transplantation far more rapidly than G-CSF (1 vs 5 days), with less toxicity to the donor. Grafts procured following plerixafor alone (P-MPB) promote full engraftment and based on a recent multi-center phase II study led by the PI, appear to reconstitute immunity faster than G-MPB and may cause less chronic GVHD (cGVHD). These advantages appear to be particularly striking in older patients receiving reduced intensity allografts. Based on these data, we hypothesize that P-MPB will become a suitable and possibly preferable alternative method to procure MPB for HCT due to the combination of better convenience and less toxicity for donors and less GVHD combined with better immune reconstitution in recipients. We propose to test these hypotheses with the following specific aims: Aim 1: We will conduct a randomized Phase II study of P-MPB versus G-MPB in recipients of matched sibling donor allografts with cGVHD-free, relapse free survival as the primary endpoint. Aim 2: We will test the hypothesis that immune reconstitution is improved with P-MPB versus G-MPB through correlative phenotypical, functional, and gene sequence based studies of T, B, NK, and dendritic cells procured from allograft recipients following HCT The proposed study addresses several key priorities of the BMT CTN established at the 2014 State of the Science Symposium and if promising will pave the way for a future definitive Phase III trial that could radically improve our process for collecting allografts from donors.