The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone
The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone
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DOI：
10.1182/blood-2005-02-0468
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发表时间：
2005-09-01
期刊：
影响因子：
20.3
通讯作者：
Calandra, G
中科院分区：
文献类型：
--
作者：
Flomenberg, N;Devine, SM;Calandra, G
造血祖细胞（HPC）通过趋化因子基质细胞衍生因子-1 α（SDF-1 α）与其受体CXC趋化因子受体4（CXCR 4）结合的营养作用运输至骨髓并保留在骨髓中。AMD 3100可逆性抑制SDF-1 α/CXCR 4结合，AMD 3100给药可动员CD 34（+）细胞进入循环。因此，我们检验了以下假设：在动员造血祖细胞（HPC）方面，AMD 3100+粒细胞集落刺激因子（G-CSF）（以下简称A + G）的组合上级单独的G-CSF（以下简称G），并且A + G动员的细胞将与G动员的细胞一样植入。主要目的是确定A + G给药与单独G给药相比，患者每单位血容量的单采是否动员了更多的祖细胞。次要目的是确定A + G动员的患者与单独G动员相比，是否需要更少的单采程序以达到至少5 × 10（6）CD 34（+）细胞/kg的移植目标水平，并确定A + G动员的患者是否具有至少90%的自体移植成功率（通过第21天的中性粒细胞植入评估）。每例患者作为他或她自己的控制在一个顺序的动员设计。达到了所有研究目的，无显著毒性。结果表明，对于自体HPC动员，A + G的组合通常是安全、有效的，并且优于单独的G上级。
Hematopoietic progenitor cells (HPCs) traffic to and are retained in the marrow through the trophic effects of the chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha) binding to its receptor, CXC chemokine receptor 4 (CXCR4). AMD3100 reversibly inhibits SDF-1 alpha/CXCR4 binding, and AMD3100 administration mobilizes CD34(+) cells into the circulation. We therefore tested the hypotheses that the combination of AMD3100 plus granulocyte colony-stimulating factor (G-CSF) (hereafter A + G) would be superior to G-CSF alone (hereafter G) in mobilizing hematopoietic progenitor cells (HPCs) and that A + G-mobilized cells would engraft as well as G-mobilized cells. The primary objective was to determine whether patients mobilized more progenitor cells per unit of blood volume of apheresis after A + G administration versus G alone. Secondary objectives were to determine whether patients mobilized with A + G compared with G alone required fewer apheresis procedures to reach the target level at least 5 X 10(6) CD34(+) cells/kg for transplantation and to determine whether patients mobilized with A + G had at least a 90% success rate of autologous transplantation as assessed by neutrophil engraftment by day 21. Each patient served as his or her own control in a sequential mobilization design. All study objectives were met without significant toxicity. The results demonstrate that the combination of A + G is generally safe, effective, and superior to G alone for autologous HPC mobilization.