Faciliation of Peripheral Blood Stem Cell Transplants by Nat

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2000年4月30日，有390万捐赠者参加了登记，并为9600例无关骨髓移植提供了便利。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，提供更多的祖细胞，比骨髓来源的细胞更快地植入，并在匹配的同胞移植环境中越来越多地被用来代替骨髓。在与供者相关的环境中，特别是在高危白血病患者中，早期良好的结果导致了在非亲缘关系的供者环境中谨慎地采用PBSC移植。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50,062人，该中心正在参与两个全国性的NMDP计划方案，一个用于获取非亲缘关系捐赠者初次移植所需的非格列格辛刺激的PBSCs，另一个用于获取用于第二次移植的PBSCs(因第一次移植后的排斥反应或肿瘤复发而必需)。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2000年4月，215名NIH无血缘关系的捐赠者接受了骨髓采集，13人接受了NMDP受者的外周血干细胞捐献。在这13例中，有10例在一次12~20升的分离过程中获得了足够的细胞用于移植。13个捐献者中有两个对非格列辛的CD34动员反应不佳，需要连续两次分离才能收集所需的细胞剂量。13条线路中没有一条需要中心线。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。非格列西汀治疗后平均白细胞数峰值为45+或-12×10的9次方/L，13例供者中有2例(15%)出现采血后血小板减少症(<100x10的9次方/L)，两人均接受过两次手术。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。由于不需要麻醉和住院，13名捐献者中有8名更喜欢G-CSF刺激的采集术而不是骨髓采集；两种手术的不适感被认为是相同的。受者的结果，包括植入时间、移植物抗宿主病的发生率和严重程度以及总体存活率尚未得到评估。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 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).