由环磷酰胺和粒细胞集落刺激因子（G-CSF）动员的CD34+细胞在功能上不同于由G-CSF动员的CD34+细胞。

CD34+ cells mobilized by cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF.

作者信息

Cesana C, Carlo-Stella C, Regazzi E, Garau D, Sammarelli G, Caramatti C, Tabilio A, Mangoni L, Rizzoli V

机构信息

Department of Hematology, University of Parma, Italy.

出版信息

Bone Marrow Transplant. 1998 Mar;21(6):561-8. doi: 10.1038/sj.bmt.1701133.

DOI:10.1038/sj.bmt.1701133

PMID:9543059

Abstract

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used as an alternative to bone marrow for autografting procedures. Currently, cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) or G-CSF alone are the most commonly used PBPC mobilization schedules. In an attempt to investigate whether the use of these two mobilization regimens could result in the collection of functionally different CD34+ cells, we analyzed nucleated cells (NC), CD34+ cells, committed progenitor cells and long-term culture initiating-cells (LTC-IC) in 52 leukaphereses from 26 patients with lymphoid malignancies, mobilized either by CY+G-CSF (n=16) or G-CSF alone (n=10). Thirty-four aphereses from the CY+G-CSF group and 18 aphereses from the G-CSF group were investigated. According to the study design, leukaphereses were carried out until an average number of 7 x 10(6) CD34+ cells/kg body weight were collected. The mean (+/-s.e.m.) numbers of CD34+ cells mobilized per apheresis by CY+G-CSF and G-CSF were not significantly different (2.76+/-0.6 x 10(8) vs 2.53+/-0.4 x 10(8), P < or = 0.7). This resulted from a mean number of NC that was significantly lower in the CY+G-CSF products than in the G-CSF products (12.4+/-1.7 x 10(9) vs 32+/-5.4 x 10(9), P < or = 0.0001) and a mean incidence of CD34+ cells that was significantly higher in the CY+G-CSF products than in the G-CSF products (2.9+/-0.6% vs 0.9+/-0.2%, P < or = 0.0018). The mean (+/-s.e.m.) number of CFU-GM collected per apheresis was significantly higher in the CY+G-CSF group than in the G-CSF group (37+/-7 x 10(6) vs 14+/-2 x 10(6), P < or = 0.03). Interestingly, CY+G-CSF-mobilized CD34+ cells had a significantly higher plating efficiency than G-CSF-mobilized CD34+ cells (25.5+/-2.9% vs 10.8+/-1.9%, P < or = 0.0006). In addition, the mean number of LTC-IC was significantly higher in the CY+G-CSF products than in the G-CSF products (6.3+/-1 x 10[6] vs 3.3+/-0.3 x 10[6], P < or = 0.05). In conclusion, our data provide evidence that CY+G-CSF and G-CSF induce the mobilization of CD34+ cells with different clonogenic potential. As mobilized PBPC containing large numbers of progenitors lead to safer transplantation, this issue may have implications for planning mobilization strategies.

摘要

动员外周血祖细胞（PBPC）越来越多地被用作骨髓的替代品用于自体移植程序。目前，环磷酰胺（CY）联合粒细胞集落刺激因子（G-CSF）或单独使用G-CSF是最常用的PBPC动员方案。为了研究这两种动员方案是否会导致收集到功能不同的CD34+细胞，我们分析了26例淋巴系统恶性肿瘤患者的52次白细胞单采产物中的有核细胞（NC）、CD34+细胞、定向祖细胞和长期培养起始细胞（LTC-IC），这些患者分别通过CY+G-CSF（n=16）或单独使用G-CSF（n=10）进行动员。研究了CY+G-CSF组的34次单采产物和G-CSF组的18次单采产物。根据研究设计，进行白细胞单采直至平均收集到7×10⁶个CD34+细胞/kg体重。CY+G-CSF和G-CSF每次单采动员的CD34+细胞的平均（±标准误）数量无显著差异（2.76±0.6×10⁸对2.53±0.4×10⁸，P≤0.7）。这是由于CY+G-CSF产物中的NC平均数量显著低于G-CSF产物（12.4±1.7×10⁹对32±5.4×10⁹，P≤0.0001），且CY+G-CSF产物中CD34+细胞的平均发生率显著高于G-CSF产物（2.9±0.6%对0.9±0.2%，P≤0.0018）。CY+G-CSF组每次单采收集的CFU-GM平均（±标准误）数量显著高于G-CSF组（37±7×10⁶对14±2×10⁶，P≤0.03）。有趣的是，CY+G-CSF动员的CD34+细胞的接种效率显著高于G-CSF动员的CD34+细胞（25.5±2.9%对10.8±1.9%，P≤0.0006）。此外，CY+G-CSF产物中的LTC-IC平均数量显著高于G-CSF产物（6.3±1×10⁶对3.3±0.3×10⁶，P≤0.05）。总之，我们的数据表明CY+G-CSF和G-CSF诱导动员具有不同克隆潜能的CD34+细胞。由于含有大量祖细胞的动员PBPC可导致更安全的移植，这个问题可能对制定动员策略有影响。