Harada M, Teshima T, Fujisaki T, Mizuno S, Miyamoto T, Takamatsu Y, Kubota A, Ohno Y, Kuroiwa M, Takenaka K, Eto T, Akashi K, Gondo H, Okamura T, Inaba S, Niho Y
Second Department of Internal Medicine, Okayama University Medical School, Japan.
Cancer Chemother Pharmacol. 1996;38 Suppl:S115-9. doi: 10.1007/s002800051051.
Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplantation, sufficient PBSC or PBPC must be infused. To confirm the utility of granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced PBSC mobilization, we investigated the effect of G-CSF on PBSC mobilization in leukemia and lymphoma patients. The study design was such that PBSC mobilization with and without G-CSF was assessed in the same patients. The results indicate that PBSC mobilization can be enhanced significantly when G-CSF is given during the recovery phase postchemotherapy. Interestingly, progenitor cells of different lineages could be mobilized by G-CSF. We subsequently investigated the effect of increasing G-CSF dose on PBSC mobilization during steady-state hematopoiesis in healthy adult donors. The results indicate that not only committed but also primitive progenitor cells are mobilized into the circulation in a dose-and time-dependent manner when G-CSF at 5, 10, or 15 micrograms/kg was given on each of 5 days and leukapheresis was performed on day 6. From our data we estimate that sufficient PBSC for engraftment after allogeneic PBSC transplantation can be collected on day 5 of administration of G-CSF at 10 micrograms/kg and by 10-1 leukapheresis on days 5 and 6. Furthermore, we found that some G-CSF-mobilized PBSC retained their self-renewal capability. These observations suggest that hematopoietic stem cells for allogeneic PBSC transplantation can be mobilized by short-term administration of relatively high-dose G-CSF.
外周血干细胞和祖细胞(PBSC和PBPC)在稳态造血过程中循环水平极低,但在骨髓抑制性化疗后的血液学恢复期间会出现短暂但显著的增加。为确保自体PBSC移植后快速且持续的血液学植入,必须输注足够的PBSC或PBPC。为证实粒细胞集落刺激因子(G-CSF)在化疗诱导的PBSC动员中的效用,我们研究了G-CSF对白血病和淋巴瘤患者PBSC动员的影响。研究设计为在同一患者中评估有或无G-CSF时的PBSC动员情况。结果表明,化疗后恢复阶段给予G-CSF时,PBSC动员可显著增强。有趣的是,不同谱系的祖细胞均可被G-CSF动员。随后,我们研究了在健康成年供体的稳态造血过程中增加G-CSF剂量对PBSC动员的影响。结果表明,当连续5天每天给予5、10或15微克/千克的G-CSF并在第6天进行白细胞分离术时,不仅定向祖细胞,而且原始祖细胞也会以剂量和时间依赖性方式被动员到循环中。根据我们的数据估计,在给予10微克/千克G-CSF的第5天以及第5天和第6天进行10-1次白细胞分离术时,可收集到足够用于异基因PBSC移植后植入的PBSC。此外,我们发现一些G-CSF动员的PBSC保留了其自我更新能力。这些观察结果表明,短期给予相对高剂量的G-CSF可动员用于异基因PBSC移植的造血干细胞。