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

国家骨髓捐赠者计划(NMDP)是 成立于1987年，至：1.创建一个志愿者登记处， 2.无血缘关系的组织型骨髓捐献者；利便 匹配的无血缘关系的供者骨髓移植通过协调 供体中心、采集中心和移植中心的巡回 中锋。截至1998年7月，320万捐助者参加了 登记和6700例无关的骨髓移植 已执行。在早期移植物丢失的移植受者中，最好的 治疗的选择通常是另一剂来自于 原始骨髓捐献者。外周血干细胞 成分，通过分离非格列替丁刺激的捐赠者而获得， 提供更多的造血祖细胞， 移植速度比骨髓来源的细胞更快。出于这些原因， 一项涉及所有参加NMDP捐助中心的议定书是 于1997年2月启动，用于第二次收购PBSCs 移植。研究的目的是：1.)要监视 非格司提单用的近期和远期安全性 健康的志愿捐赠者；2)比较……的不利影响 骨髓与外周血干细胞捐赠；以及3.)要监视 匹配的非亲属供者外周血干细胞移植的结果，包括 植入时间、急性和慢性移植物抗宿主病的发生率 无病生存率和总存活率。截至1998年8月，33 无血缘关系的NMDP捐赠者每天接受10微克/公斤/天的FILGRATIM治疗，共5次 几天，然后进行分离。17名捐赠者接受了一次 手术中，15例接受了两次手术，没有一例需要中线 放置。所有捐献者都经历了粒细胞集落刺激 因素引起的疲劳、失眠、骨痛或头痛，尽管 只有6%的捐赠者被认为这些影响是严重的。 治疗后平均白细胞峰值为46‘12×10~4 9次方/L，及采后血小板减少症(< 100x10的9次方/L)发生5例(15%)，全部 他接受了两次手术。平均完工时间 从PBSC捐献中恢复的时间为1周，而之前为3周 用来采集骨髓。产品CD34内容和收件人 结果，包括植入时间、急性和慢性移植物抗宿主病 在受者身上，总体存活率还没有 美国国立卫生研究院骨髓捐献中心，参与 NMDP的登记册上有48,000名捐赠者。185 NIH无关的捐赠者接受了骨髓采集，其中6人 接受NMDP受助者的PBSC捐赠。足够的单元格用于 移植是在一次12‘18升的分离过程中获得的 这六个案子都是。同日CD34血流分析的可用性 允许准确量化产品内容，并避免 需要额外的分离程序。六个捐赠者中的五个 与骨髓采集相比，更倾向于通过分离的方式捐献PBSC，因为 不需要麻醉和住院治疗。的不适 这两个程序被认为是等同的。 这项全国性研究的调查人员在DTM/CC(SFL和 DS)。为这项研究提供的行政和统计支持是 由NMDP全国办公室提供。提供了filgratim 根据与安进达成的一项研究新药协议 (BB-IND#6821)。

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).