Peripheral Blood Stem Cell Collections From NMDP Donors

国家骨髓捐赠计划（NMDP）成立于1987年，目的是：(1)建立志愿者、组织型、非亲属骨髓捐赠者的登记；(2)通过捐赠者、收集和移植中心的协调循环，促进匹配的非亲属骨髓移植。截至2005年8月31日，共有580万捐赠者参与了登记，并促成了超过2万例无关干细胞移植。外周血干细胞（PBSC）成分，通过非格昔汀刺激供体的分离获得，提供比骨髓来源的干细胞更快移植的大量祖细胞，目前在相关和非相关供体环境中都超过了骨髓的使用。NIH骨髓捐赠中心是参与NMDP网络的最大的医院捐赠中心之一，其注册有55,000名捐赠者，正在参与全国性的NMDP协议，通过非相关捐赠者的血浆获取非格拉西汀刺激的PBSCs。这些研究的目的是：(1)监测非格司汀在健康志愿供体中的安全性，(2)比较骨髓与PBSC捐赠的不良反应，(3)监测匹配的非相关供体PBSC移植的结果，包括移植时间、GVHD发生率、无病生存期和总生存期。截至2006年8月31日，139名NIH捐赠者为不相关的NMDP受赠者进行了159次血浆分离程序收集PBSC。139例中有120例（86%）仅需单次单采即可收集足够剂量的细胞用于移植。139名献血者中有6名（均为女性）需要中央静脉输注。所有的供者都经历了g - csf引起的疲劳、失眠、骨痛或头痛，尽管只有6%的供者认为这些影响是严重的。非格昔汀后平均白细胞计数峰值为40,100/uL， 139名献血者中有15名（11%）发生采后血小板减少（少于100,000/uL），其中9名接受了两次手术。骨髓移植后的平均恢复时间为1周，而骨髓移植后的平均恢复时间为3周。16名同时捐献骨髓和PBSC的捐赠者中，有11名由于不需要麻醉和住院治疗，更倾向于g - csf刺激的单采捐赠而不是骨髓采集；两种手术的不适被认为是相同的。对NMDP受者结果的分析表明，与骨髓移植相比，PBSC移植与减少移植时间和改善急性移植相关发病率相关。然而，与骨髓移植相比，骨髓移植的GVHD发病率和严重程度增加，因此两种不相关移植的1年总生存率没有差异。这项研究的行政和统计支持由新民主党国家办公室提供。Filgrastim是根据安进的IND协议提供的（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, collection, and transplant centers. As of August 31, 2005, 5.8 million donors were participating in the registry and greater than 20,000 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 stem cells, and are currently exceeding the use of marrow in both related and unrelated donor settings. The NIH Marrow Donor Center, one of the largest hospital-based donor centers participating in the NMDP network, with 55,000 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 August 31, 2006, 139 NIH donors had undergone 159 apheresis procedures to collect PBSC's for unrelated NMDP recipients. 120 of 139 (86%) required only a single apheresis procedure to collect an adequate cell dose for transplant. Six of the 139 donors, all female, required a central line. All donors experienced G-CSF-induced fatigue, insomnia, bone pain, or headache, although in only 6% were these effects considered severe. Peak mean leukocyte counts after filgrastim were 40,100/uL, and postapheresis thrombocytopenia (less than 100,000/uL) occurred in 15 of 139 donors (11%), nine of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Eleven of 16 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).