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）建立一个志愿者、组织型、无关骨髓捐献者的登记处，（2）通过捐献者、收集和移植中心的协调回路促进匹配的无关捐献者骨髓移植。截至2005年8月31日，有580万名捐献者参加了登记，并为20 000多例无关干细胞移植提供了便利。通过非格司亭刺激的供体的单采血液成分术收获的外周血干细胞（PBSC）组分提供了比骨髓来源的干细胞更快地移植的更大量的祖细胞，并且目前超过了在相关和不相关供体环境中使用骨髓。NIH骨髓捐献中心是参与NMDP网络的最大的医院捐献中心之一，其登记册上有55，000名捐献者，正在参与一项全国性的NMDP方案，通过对无关捐献者进行单采术来获取非格司亭刺激的PBSC。这些研究的目的是（1）监测健康志愿者供体中非格司亭给药的安全性，（2）比较骨髓与PBSC捐献的不良反应，（3）监测匹配的无关供体PBSC移植的结局，包括植入时间、GVHD发生率以及无病生存期和总生存期。截至2006年8月31日，139名NIH捐献者接受了159次单采程序，为无关的NMDP接受者收集PBSC。139例患者中有120例（86%）仅需单次单采术即可收集足够的细胞用于移植。139名献血者中有6名（均为女性）需要中心静脉导管。所有供体均经历了G-CSF诱导的疲劳、失眠、骨痛或头痛，尽管仅6%的供体认为这些影响严重。非格司亭后白细胞计数峰值平均值为40，100/uL，139名供体中有15名（11%）发生了单采后血小板减少症（低于100，000/uL），其中9名接受了两次手术。从PBSC捐献到完全恢复的平均时间为1周，而骨髓收获为3周。由于不需要麻醉和住院治疗，16名捐献骨髓和PBSC的供体中有11名更喜欢G-CSF刺激的单采捐献，而不是骨髓收获;认为两种程序的不适是等同的。对NMDP受体结局的分析表明，与骨髓移植相比，PBSC移植与植入时间缩短和急性移植相关发病率改善相关。然而，移植物抗宿主病的发病率和严重程度与骨髓移植相比，PBSC增加，因此，在一年的总生存率是没有不同的两种类型的无关移植。这项研究的行政和统计支持由NMDP国家办公室提供。非格司亭是根据与安进的IND协议（BB-IND #6821）提供的。

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).