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愈性治疗， 急性和慢性移植物抗宿主病（GVHD）继续困扰该领域，并且常常限制了移植物的寿命， 患者的生活质量。而骨髓（BM）或动员的外周血（MPB）是合适的 供体造血细胞的来源，该网络在BMT CTN 0201中建立了粒细胞集落， 刺激因子（G-CSF）MPB与慢性GVHD（cGVHD）的风险较高和 与BM相比，无关供体HCT后的寿命。类似的结果也在接受 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，具有良好的生产力记录 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， 为移植用供体造血细胞的获取建立新的标准。OSUBMT- RC PI开创了一种使用CXCR 4拮抗剂plerixafor获得HCT供体细胞的新方法 没有G-CSF。Plerixafor动员CD 34+细胞和其他免疫细胞用于移植的速度远远快于 G-CSF（1 vs 5天），对供体的毒性较小。普乐沙福单药治疗（P-MPB）后获得的移植物促进 完全植入并基于PI领导的最近多中心II期研究，似乎可重建免疫力 比G-MPB更快，并且可能引起更少的慢性GVHD（cGVHD）。这些优势似乎特别 在接受低强度同种异体移植的老年患者中尤为明显。基于这些数据，我们假设P-MPB 将成为一种合适的和可能优选的替代方法，以获得用于HCT的MPB，因为 结合更好的方便性和对供体的毒性更小以及GVHD更少结合更好的免疫 在接受者中重建。我们建议以下列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与G-MPB的随机II期研究。 以无cGVHD、无复发生存率作为主要终点的同胞供体同种异体移植物。 目的2：我们将检验P-MPB与G-MPB相比能改善免疫重建的假设 通过对T、B、NK和树突状细胞的相关表型、功能和基因序列的研究， 从HCT后的同种异体移植物受体中获得的细胞 拟议的研究解决了2014年国家建立的BMT CTN的几个关键优先事项， 科学研讨会，如果有希望的话，将为未来确定的III期试验铺平道路， 改进我们从捐赠者那里收集同种异体移植物的程序

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.