Faciliation of Peripheral Blood Stem Cell Transplants by Nat

Nat 促进外周血干细胞移植

• 批准号: 6431823
• 负责人: SUSAN F LEITMAN-KLINMAN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431823
• 关键词: blood banks; blood donor; blood treatment; bone marrow transplantation; clinical research; colony stimulating factor; hematopoietic stem cells; human subject; longitudinal human study

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).

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2000年4月30日，有390万名捐赠者参加了登记，并促成了9 600例无关骨髓移植。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细胞更快地移植的更大量的祖细胞，并且在匹配的同胞移植设置中越来越多地用于代替骨髓。在相关供体环境中，特别是在高危白血病患者中，早期良好的结果导致在无关供体环境中谨慎采用PBSC移植。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，其登记处有50，062名捐献者，正在参与两个全国性的NMDP方案，一个用于获得非格司亭刺激的PBSC用于主要无关供体移植，另一个用于获得PBSC用于第二次移植（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2000年4月，215名NIH无关供体接受了骨髓收获，13名接受了NMDP受体的PBSC捐献。在这13例中的10例中，在一次12至20升的单采程序中获得了足够的细胞用于移植。13名供体中有2名对非格司亭的CD 34动员反应较差，需要连续两次单采术来采集所需的细胞剂量。这13例患者均不需要中心静脉导管。所有捐赠者都经历了G-CSF诱导的疲劳，失眠，骨痛或头痛，尽管只有8%的人认为这些影响严重。非格司亭后白细胞计数峰值平均值为45 ± 12 × 10的9次方/L，13名供体中有2名（15%）发生了单采后血小板减少症（小于100 × 10的9次方/L），这两名供体都接受了两次手术。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，13名供体中有8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程度相当。移植物结局，包括移植时间、GVHD发生率和严重程度以及总生存率尚未进行评估。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。