Faciliation of Peripheral Blood Stem Cell Transplants by Nat

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2000年4月30日，共有390万名捐赠者参与了登记，并促成了9600例无关骨髓移植。外周血干细胞（PBSC）成分，通过非格昔汀刺激供体的分离获得，提供比骨髓源性细胞更快的大量祖细胞，并且越来越多地用于匹配的兄弟姐妹移植环境中代替骨髓。在无血缘关系的供体环境中，特别是在高风险白血病患者中，早期良好的结果导致在无血缘关系的供体环境中谨慎采用PBSC移植。NIH骨髓供体中心是参与NMDP网络的最大的医院供体中心之一，在其注册中有50,062名供体，正在参与两个全国性的NMDP方案，一个用于获取非格昔汀刺激的PBSCs用于原发非相关供体移植，另一个用于获取PBSCs用于第二次移植（由于第一次移植后的排斥反应或肿瘤复发）。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2000年4月，215名与NIH无关的捐赠者接受了骨髓采集，13名接受了NMDP接受者的PBSC捐赠。在这13例病例中，有10例在一次12至20升的单采过程中获得了足够的移植细胞。13名供者中有2名对非格拉西汀的CD34动员反应较差，需要连续两次分离程序来收集所需的细胞剂量。13个都不需要中央静脉。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8%的人认为这些影响是严重的。非格拉西汀后的峰值平均白细胞计数为45±12 × 10的9次方/L，采后血小板减少症（小于100 × 10的9次方/L）发生在13名供者中的2名（15%），他们都接受了两次手术。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。由于不需要麻醉和住院治疗，13名捐赠者中有8名更倾向于g - csf刺激的采珠捐赠而不是骨髓采集；两种手术的不适被认为是相同的。受体结果，包括移植时间，GVHD发病率和严重程度，以及总生存期尚未评估。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 April 30, 2000, 3.9 million donors were participating in the registry and 9,600 unrelated marrow 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 the matched sibling transplant setting. Early favorable outcomes in the related-donor setting, particularly in patients with high-risk leukemia, have led to the cautious adoption of PBSC transplants in the unrelated donor setting. The NIH Marrow Donor Center, one of the largest hospital-based donor centers participating in the NMDP network, with 50,062 donors on its registry, is participating in two nationwide NMDP protocols, one for acquisition of filgrastim-stimulated PBSCs for primary unrelated donor transplant, and one for acquisition of PBSCs for second transplants (necessitated by rejection or tumor recurrence after a first transplant). 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 April 2000, 215 NIH unrelated donors had undergone marrow harvest and 13 had undergone PBSC donation for NMDP recipients. Sufficient cells for transplant were obtained in one 12 to 20 liter apheresis procedure in ten of these 13 cases. Two of 13 donors had poor CD34 mobilization responses to filgrastim, and needed two consecutive apheresis procedures to collect the requested cell dose. None of the 13 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 plus or minus 12 x 10 to the ninth power/L, and postapheresis thrombocytopenia (less than 100 x 10 to the ninth power/L) occurred in two of 13 donors (15 percent), both of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Eight of 13 donors 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. Recipient outcomes, including time to engraftment, GVHD incidence and severity, and overall survival have not yet been evaluated. 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).