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自体外周血祖细胞移植

Autologous peripheral blood progenitor cell transplantation.

作者信息

Anderson K C

机构信息

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

出版信息

J Clin Apher. 1995;10(3):131-8. doi: 10.1002/jca.2920100307.

DOI:10.1002/jca.2920100307
PMID:8582895
Abstract

Harvesting of autologous peripheral blood stem cells (PBSCs) has been facilitated by using currently available, efficient apheresis technology at the time of rebound from chemotherapy while patients are receiving recombinant growth factors, i.e., granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF). Ideally pheresis should be done before patients have had extensive stem cell toxins, i.e., alkylating agents or nitrosoureas. This strategy has facilitated the use of high dose chemoradiotherapy given as a single regimen or in a divided dose for patients with solid tumors or hematologic malignancies and results in more rapid engraftment than bone marrow transplantation (BMT). Although there are no assays which measure repopulating stem cells, enumeration of CD34+ cells within PBSCs is a direct and rapid assay which provides an index of both early and late long-term reconstitutive capacity, since it correlates with colony-forming unit (CFU)-GMs, as well as pre-progenitor or delta assays and long-term culture-initiating cells (LTC-IC). A threshold of > or = 2 x 10(6) CD34+ cells/kg recipient body weight has been reported to be required for engraftment, but may vary depending upon the clinical setting. Strategies for mobilization of normal PBSCs also increase tumor cell contamination within PB in the setting of both hematologic malignancies and solid tumors, but the significance of these tumor cells in terms of patient outcome is unclear. Recently isolation of CD34+ cells from PBSCs has been done using magnetic beads or immunoabsorption on columns or rigid plates in order to enrich for normal hematopoietic progenitors and potentially decrease tumor cell contamination. As for other cellular blood components, standards have been developed to assure efficient collection and processing, thawing, and reinfusion, and to maintain optimal PBPC viability. Finally, future directions of clinical research include expansion of hematopoietic progenitor cells ex vivo; use of umbilical cord or placenta as rich sources of progenitor cells; syngeneic hematopoietic stem cell transplantation; related and unrelated allogeneic hematopoietic stem cell transplantation; treatment of infections, i.e., Epstein Barr virus, or tumor relapse after allogeneic BMT using donor PBSC infusions; and gene therapy approaches.

摘要

在患者接受重组生长因子(即粒细胞(G)或粒细胞 - 巨噬细胞(GM)集落刺激因子(CSF))治疗且化疗后病情反弹时,利用当前可用的高效单采技术,已便于采集自体外周血干细胞(PBSC)。理想情况下,单采应在患者接触大量干细胞毒素(即烷化剂或亚硝基脲)之前进行。该策略促进了高剂量放化疗在实体瘤或血液系统恶性肿瘤患者中的应用,可采用单一方案或分剂量给药,且与骨髓移植(BMT)相比,能使造血干细胞更快植入。虽然目前尚无检测重建造血干细胞的方法,但对PBSC中CD34 +细胞进行计数是一种直接且快速的检测方法,它能提供早期和晚期长期重建造血能力的指标,因为它与集落形成单位(CFU) - GM相关,也与祖细胞前体或δ检测以及长期培养起始细胞(LTC - IC)相关。据报道,植入所需的阈值为≥2×10⁶ CD34 +细胞/千克受者体重,但可能因临床情况而异。在血液系统恶性肿瘤和实体瘤患者中,动员正常PBSC的策略也会增加PB中的肿瘤细胞污染,但这些肿瘤细胞对患者预后的影响尚不清楚。最近,已通过使用磁珠或在柱或刚性板上进行免疫吸附从PBSC中分离CD34 +细胞,以富集正常造血祖细胞并可能减少肿瘤细胞污染。对于其他细胞血液成分,已制定标准以确保高效采集、处理、解冻和回输,并维持最佳的PBPC活力。最后,临床研究的未来方向包括体外扩增造血祖细胞;使用脐带或胎盘作为丰富的祖细胞来源;同基因造血干细胞移植;相关和无关供体的异基因造血干细胞移植;治疗感染(如EB病毒)或在异基因BMT后使用供体PBSC输注治疗肿瘤复发;以及基因治疗方法。

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