Acquisition of Hematopoietic Stem Cells for Second Transplants by Apheresis of Fi

通过 Fi 血浆分离术获取用于第二次移植的造血干细胞

• 批准号: 6103656
• 负责人: SUSAN F LEITMAN-KLINMAN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6103656
• 关键词: blood banks; blood donor; blood treatment; bone marrow transplantation; clinical research; colony stimulating factor; hematopoietic stem cells; human subject; longitudinal human study

The National Marrow Donor Program (NMDP) was established in 1987 to: 1.) create a registry of volunteer, tissue-typed, unrelated bone marrow donors; and 2.) facilitate matched unrelated donor marrow transplants through a coordinated circuit of Donor Centers, Collection Centers, and Transplant Centers. As of July 1998, 3.2 million donors were participating in the registry and 6,700 unrelated marrow transplants had been performed. In transplant recipients with early graft loss, the best option for therapy is often another dose of stem cells from the original marrow donor. Peripheral blood stem cell (PBSC) components, harvested by apheresis of filgrastim-stimulated donors, provide larger numbers of hematopoietic progenitor cells that engraft more rapidly than marrow-derived cells. For these reasons, a protocol involving all participating NMDP Donor Centers was initiated in February 1997, for the acquisition of PBSCs for second transplants. The objectives of the study are: 1.) to monitor the immediate and long-term safety of filgrastim administration in healthy volunteer donors; 2.) to compare the adverse effects of bone marrow versus PBSC donation; and 3.) to monitor the outcome of matched unrelated-donor PBSC transplants, including time to engraftment, incidence of acute and chronic GVHD, and disease-free and overall survival rates. As of August 1998, 33 unrelated NMDP donors received filgrastim 10 ug/kg/day SQ for 5 days, followed by apheresis. Seventeen donors underwent one procedure, 15 underwent two, and none required central line placement. All donors experienced granulocyte colony stimulating factor-induced fatigue, insomnia, bone pain or headache, although in only 6 percent of donors were these effects considered severe. Peak mean leukocyte counts after filgrastim were 46 ' 12 x 10 to the 9th power/L, and postapheresis thrombocytopenia (less than 100 x 10 to the 9th power/L) occurred 5 donors (15 percent), all of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Product CD34 content, and recipient outcomes, including time to engraftment, acute and chronic GVHD in the recipient, and overall survival have not yet been evaluated.The NIH Marrow Donor Center, a participant in the NMDP, has 48,000 donors on its registry. One hundred eighty-five NIH unrelated donors have undergone marrow harvest and six have undergone PBSC donation for NMDP recipients. Sufficient cells for transplant were obtained in one 12'18 liter apheresis procedure in all six cases. The availability of same-day CD34 flow analysis permitted exact quantitation of product content and avoided the need for additional apheresis procedures. Five of six donors preferred PBSC donation by apheresis to marrow harvest due to the lack of need for anesthesia and hospitalization. The discomfort of the two procedures was considered equivalent.Two of the principal investigators for this national study are in the DTM/CC (SFL and DS). Administrative and statistical support for the study are provided by the NMDP National Office. Filgrastim is provided under an Investigational New Drug agreement with Amgen (BB-IND # 6821).

国家骨髓捐献者计划（NMDP） 成立于1987年：1。建立一个志愿者登记册， 组织分型的无关骨髓供体;和2.）促进 通过一个协调的匹配无关的捐赠者骨髓移植， 供体中心、收集中心和移植中心的循环 中心.截至1998年7月，有320万捐助者参加了 登记处和6,700例无关的骨髓移植， 执行。对于早期移植物丢失的移植受者， 治疗的选择通常是另一剂干细胞， 原始骨髓捐赠者外周血干细胞 组分，通过非格司亭刺激的供体的单采血液成分术收获， 提供大量的造血祖细胞， 比骨髓来源的细胞移植更快。基于这些理由， 涉及所有参与NMDP的供体中心的方案是 1997年2月开始， 移植本研究的目的是：（1）。监测 非格司亭给药即刻和长期安全性 健康的志愿者供体; 2.）来比较 骨髓与PBSC捐赠;以及3.）监测 匹配的无关供体PBSC移植的结局，包括 植入时间、急性和慢性GVHD的发生率，以及 无病生存率和总生存率。截至1998年8月， 无关的NMDP供体接受非格司亭10 ug/kg/天SQ，持续5 天，随后进行单采。17名捐赠者接受了一次 手术，15例接受了2例，无一例需要中心线 安置所有供体均接受了粒细胞集落刺激 因素引起的疲劳，失眠，骨痛或头痛，虽然 只有6%的捐赠者认为这些影响严重。 非格司亭治疗后白细胞计数的峰值平均值为46 × 12 × 10 ~（-1）， 9次幂/L，以及单采后血小板减少症（小于 100 × 10的9次方/L）发生5例供体（15%），均为 她经历了两次手术。平均完成时间 PBSC捐献后的恢复期为1周， 进行骨髓采集产品CD 34内容和收件人 结局，包括植入时间、急性和慢性GVHD 在接受者中，总体生存率尚未被 NIH骨髓捐赠中心，参与了 NMDP在其登记册上有48，000名捐助者。一百八十五 NIH无关的捐赠者进行了骨髓收获，6人 为NMDP接受者提供PBSC捐赠。足够的细胞， 在一个12 × 18升的单采血液成分术程序中获得移植物， 所有六个案子当天CD 34流量分析的可用性 允许产品含量的精确定量，并避免 需要额外的单采程序。六个捐赠者中的五个 首选通过单采血液成分术捐献PBSC以获取骨髓，因为 无需麻醉和住院治疗。的不适 这两个程序被认为是等同的。两个主要的 这项国家研究的研究者在DTM/CC（SFL和 DS）。研究的行政和统计支持是 由NMDP国家办公室提供。提供非格司亭， 根据与安进公司的研究性新药协议 （BB-IND # 6821）。