Stem Cell Transplantation: Basic/Clinical Research

干细胞移植：基础/临床研究

• 批准号: 7478455
• 负责人: Rainer F. Storb
• 金额: $ 266.02万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478455
• 关键词: Stem; Cell; Transplantation; Basic; Clinical

DESCRIPTION (provided by applicant): We propose to continue an integrated program of basic and clinical research to improve treatment of patients with acquired and inherited nonmalignant blood disorders and myelodysplastic syndromes by hematopoietic cell transplantation (HCT). The two clinical projects pursue two shared overall objectives for allogeneic HCT. One is to reduce conditioning-related toxicities and transplantation associated complications including graft rejection and graft-versus-host disease (GVHD). The other is to broaden the choice of hematopoietic cell donors beyond HLA-matched related and unrelated individuals by including grafts of HLA-haploidentical marrow cells and unrelated cord blood. The two preclinical projects will use a canine model with a long history of successful translation into clinical trials. One Project seeks to further improve major histocompatibility complex haploidentical HCT, in part by exploring combinations of biological and pharmacological immunosuppressive agents and in part by exploring novel post-transplantation chemotherapy strategies in combination with methods of transfer of drug resistance genes developed The other Project proposes to further optimize efficacy and safety of gene transfer into hematopoietic cells, test the therapeutic efficacy and safety of gene transfer in a clinically relevant canine inherited blood disorder, and study long-term consequences of gene transfer. The four research projects are supported by four core units, which provide study design, data processing, statistical analyses, protocol management, and coordination of multi-center trials, assessment of immune functions after transplantation, management of chronic GVHD,and long-term follow-up. The principles derived from the studies under this grant have had and will continue to have broad implications for marrow and blood stem cell transplantation and gene therapy in the treatment of patients with other malignant and nonmalignant blood disorders.

描述（由申请人提供）： 我们建议继续进行基础和临床研究的综合计划，以改善造血细胞移植（HCT）对获得性和遗传性非恶性血液病和骨髓增生异常综合征患者的治疗。这两个临床项目追求同种异体HCT的两个共同的总体目标。一个是减少条件相关毒性和移植相关并发症，包括移植物排斥和移植物抗宿主病（GVHD）。另一个是扩大造血细胞供体的选择范围，包括HLA半相合骨髓细胞和无关脐带血的移植物，而不仅仅是HLA相合的相关和无关个体。这两个临床前项目将使用一种具有长期成功转化为临床试验历史的犬模型。一个项目寻求进一步改善主要组织相容性复合体单倍体相合HCT，部分通过探索生物和药理学免疫抑制剂的组合，部分通过探索新的移植后化疗策略与开发的耐药基因转移方法的组合。另一个项目提出进一步优化基因转移到造血细胞中的功效和安全性，测试基因转移在临床相关犬遗传性血液病中的治疗效果和安全性，并研究基因转移的长期后果。这四个研究项目由四个核心单位支持，提供研究设计，数据处理，统计分析，方案管理，多中心试验协调，移植后免疫功能评估，慢性GVHD管理和长期随访。从这项资助下的研究中得出的原则已经并将继续对骨髓和血液干细胞移植以及治疗其他恶性和非恶性血液疾病患者的基因治疗产生广泛的影响。