Peripheral Blood Stem Cell Collections From NMDP Donors

国家骨髓捐献者计划(NMDP)成立于1987年，目的是(1)建立志愿者、组织型、无关骨髓捐赠者的登记，(2)通过捐赠者、采集者和移植中心的协调循环，促进匹配的无关捐赠者的骨髓移植。截至2002年8月31日，有480万捐赠者参与了登记，并为14859例无关干细胞移植提供了便利。外周血干细胞(PBSC)成分，通过采集受非格列西汀刺激的捐献者，提供了更多的祖细胞，比骨髓来源的细胞更快地植入，并且在相关和非相关捐赠者的环境中越来越多地被用来代替骨髓。NIH骨髓捐赠者中心是参与NMDP网络的最大的医院捐赠者中心之一，登记在册的捐赠者有62,000人，该中心正在参与一项全国性的NMDP计划方案，通过分离无关捐赠者的方式获取非格列汀刺激的PBSCs。这些研究的目的是(1)监测在健康志愿者捐献者中应用非格列汀的安全性，(2)比较骨髓和外周血干细胞捐献的不良反应，以及(3)监测匹配的无关供者外周血干细胞移植的结果，包括植入时间、移植物抗宿主病(GVHD)的发生率以及无病和总存活率。截至2002年9月30日，61名NIH捐献者接受了79次采集术，为无血缘关系的NMDP受者采集PBSC。61例中有44例(72%)只需一次分离程序即可收集足够的细胞剂量用于移植。61例中有17例对非格列辛的CD34动员反应较差，需要连续两次分离才能获得足够的细胞剂量。在61名捐赠者中，有三人都是女性，需要一条中心线。所有捐献者都经历了G-CSF引起的疲劳、失眠、骨痛或头痛，尽管只有8%的人认为这些影响很严重。在61名捐献者中，有9人(15%)在接受了两次手术后出现了采血后的血小板减少症(<100,000/ul)。捐献PBSC后完全康复的平均时间为1周，而骨髓采集组为3周。在同时捐献骨髓和外周血干细胞的15名捐赠者中，由于不需要麻醉和住院，10名捐赠者更喜欢G-CSF刺激的分离捐赠而不是骨髓采集；两种程序的不适感被认为是相同的。对NMDP受者结局的分析表明，与骨髓移植相比，PBSC移植可以减少植入时间，并改善急性移植相关的发病率。然而，与骨髓移植相比，外周血干细胞移植可增加移植物抗宿主病的发生率和严重程度，因此两种类型的非亲缘移植的一年总存活率没有差别。全国民运计划全国办公室为这项研究提供行政和统计支助。根据与安进的IND协议(BB-IND#6821)提供文件。

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, collection, and transplant centers. As of August 31, 2002, 4.8 million donors were participating in the registry and 14,859 unrelated stem cell transplants had been facilitated. Peripheral blood stem cell (PBSC) components, harvested by apheresis of filgrastim-stimulated donors, provide larger numbers of progenitor cells which engraft more rapidly than marrow-derived cells, and are being increasingly used instead of marrow in both the related and unrelated donor settings. The NIH Marrow Donor Center, one of the largest hospital-based donor centers participating in the NMDP network, with 62,000 donors on its registry, is participating in a nationwide NMDP protocol for the acquisition of filgrastim-stimulated PBSCs by apheresis of unrelated donors. The objectives of these studies are (1) to monitor the 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 GVHD, and disease free and overall survival. As of September 30, 2002, 61 NIH donors had undergone 79 apheresis procedures to collect PBSC's for unrelated NMDP recipients. 44 of 61 (72%) required only a single apheresis procedure to collect an adequate cell dose for transplant. 17 of 61 had a poor CD34 mobilization response to filgrastim, and needed two consecutive apheresis procedures to collect an adequate cell dose. Three of the 61 donors, all female, required a central line. All donors experienced G-CSF-induced fatigue, insomnia, bone pain, or headache, although in only 8 percent were these effects considered severe. Peak mean leukocyte counts after filgrastim were 45,500/uL, and postapheresis thrombocytopenia (less than 100,000/uL) occurred in 9 of 61 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. Ten of 15 donors who had donated both marrow and PBSC preferred G-CSF-stimulated apheresis donations to marrow harvest due to the lack of need for anesthesia and hospitalization; discomfort of the two procedures was considered equivalent. Analysis of NMDP recipient outcomes shows that PBSC transplants are associated with reduced times to engraftment and improved acute transplant-related morbidity compared with marrow transplants. However, GVHD incidence and severity are increased with PBSC versus marrow grafts, so that overall survival at one year is not different among the two types of unrelated transplants. Administrative and statistical support for this study is provided by the NMDP National Office. Filgrastim is provided under an IND agreement with Amgen (BB-IND #6821).