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重组人粒细胞集落刺激因子在干细胞移植中的应用现状

The changing face of stem cell transplantation by the use of recombinant human granulocyte colony stimulating factor.

作者信息

Boogaerts M A, Demuynck H

机构信息

Department of Hematology, University Leuven, U.Z. Gasthuisberg, Belgium.

出版信息

Eur J Cancer. 1994;30A Suppl 3:S34-9.

PMID:7535071
Abstract

The use of peripheral blood progenitor cells (PBPC) for autografting following high-dose chemotherapy in a variety of malignancies has increased markedly with the advent of efficacious and safe myeloid growth factors, which have dramatically improved collection yields. There is still controversy as to whether PBPC should be harvested after a combination of chemotherapy and growth factors, or after growth factors alone. The use of powerful combinations of newer growth factors, such as interleukin-3 with granulocyte-macrophage colony stimulating factor (GM-CSF), or granulocyte colony stimulating factor (G-CSF) with stem cell factor, may obviate the need for chemotherapy. The problem of providing sufficient numbers of PBPC for successful transplantation and sustained engraftment has led to the development of a variety of in vitro expansion systems for stem cells, using cocktails of growth factors. Single blood collections may contain sufficient CD34+ cells to be expanded on a large scale for clinical transplantation, eliminating costly and labour intensive apheresis procedures. PBPC transplants may carry less risk for contamination with malignant cells; however, sensitive detection techniques have revealed that tumour cell contamination of PBPC harvests may be much more prevalent than was previously suspected and both positive and negative selection of CD34+ cells for clinical transplantation is being investigated. PBPC transplantation generally results in more rapid engraftment, with faster recovery of neutrophils and platelets, compared with autologous bone marrow transplants. In most studies, PBPC transplants also resulted in fewer septic episodes, fewer intensive care admissions, fewer transfusions of red blood cells and platelets, reduced antibacterial and parenteral nutrition use, and reduced hospital costs. Dose optimisation and intensification of chemotherapy, relying on repeated administration of growth factor-mobilised PBPC, offers interesting prospects in the treatment of a variety of tumours. However, well-controlled, randomised prospective trials will be needed to prove the real value of PBPC transplants with regard to survival and cure. In the clinical setting, PBPC transplantations are likely to replace autologous marrow transplants in the near future. Manipulation of PBPC in vitro, i.e. expansion or gene transfer, may prove to be the most exciting perspective in the treatment of both malignant and non-malignant haematological conditions.

摘要

随着有效且安全的髓系生长因子的出现,外周血祖细胞(PBPC)在多种恶性肿瘤大剂量化疗后用于自体移植的应用显著增加,这些生长因子极大地提高了采集产量。对于PBPC是应在化疗与生长因子联合使用后采集,还是仅在生长因子使用后采集,仍存在争议。使用新型生长因子的强效组合,如白细胞介素 - 3与粒细胞 - 巨噬细胞集落刺激因子(GM - CSF),或粒细胞集落刺激因子(G - CSF)与干细胞因子,可能无需进行化疗。为成功移植和持续植入提供足够数量的PBPC这一问题,促使人们开发了多种使用生长因子鸡尾酒的干细胞体外扩增系统。单次采血可能含有足够数量的CD34 +细胞,可大规模扩增用于临床移植,从而省去了昂贵且劳动强度大的单采程序。PBPC移植可能降低恶性细胞污染的风险;然而,灵敏的检测技术表明,PBPC采集物中肿瘤细胞污染可能比以前怀疑的更为普遍,目前正在研究用于临床移植的CD34 +细胞的阳性和阴性选择。与自体骨髓移植相比,PBPC移植通常导致更快的植入,中性粒细胞和血小板恢复更快。在大多数研究中,PBPC移植还导致脓毒症发作减少、重症监护入院减少、红细胞和血小板输血减少、抗菌药物和肠外营养使用减少以及医院成本降低。依靠重复给予生长因子动员的PBPC进行化疗剂量优化和强化,在多种肿瘤的治疗中提供了有趣的前景。然而,需要进行严格对照的随机前瞻性试验来证明PBPC移植在生存和治愈方面的真正价值。在临床环境中,PBPC移植在不久的将来可能会取代自体骨髓移植。在体外对PBPC进行操作,即扩增或基因转移,可能被证明是治疗恶性和非恶性血液学疾病最令人兴奋的前景。

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