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通过单剂量给予CXCR4拮抗剂AMD3100,增强从用粒细胞集落刺激因子刺激的正常人类志愿者中动员和收集CD34+造血细胞。

Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist.

作者信息

Liles W Conrad, Rodger Elin, Broxmeyer Hal E, Dehner Christine, Badel Karin, Calandra Gary, Christensen Jeff, Wood Brent, Price Thomas H, Dale David C

机构信息

Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

出版信息

Transfusion. 2005 Mar;45(3):295-300. doi: 10.1111/j.1537-2995.2005.04222.x.

Abstract

BACKGROUND

AMD3100, a selective antagonist of CXCR4, rapidly mobilizes CD34+ hematopoietic progenitor cells (HPCs) from marrow to peripheral blood with minimal side effects.

STUDY DESIGN AND METHODS

To further investigate potential clinical utility of AMD3100 for CD34+ cell mobilization and collection, a Phase I study in normal volunteers was performed examining single-dose administration of AMD3100 alone and in combination with a standard 5-day granulocyte-colony-stimulating factor (G-CSF) regimen.

RESULTS

AMD3100 (160 microg/kg x 1 on Day 5) significantly increased both G-CSF-stimulated (10 microg/kg/day) mobilization of CD34+ cells (3.8-fold) and leukapheresis yield of CD34+ cells. Moreover, collection of CD34+ cells was comparable between individuals mobilized by a single-dose regimen of AMD3100 (240 microg/kg) and individuals mobilized with a 5-day regimen of G-CSF. AMD3100-mobilized leukapheresis products contained significantly greater numbers of T and B cells compared to G-CSF-stimulated leukapheresis products.

CONCLUSION

These findings indicate that AMD3100 can be used alone or as an adjunct to G-CSF to mobilize cells for HPC transplantation.

摘要

背景

AMD3100是一种CXCR4的选择性拮抗剂,能以最小的副作用将CD34+造血祖细胞(HPC)从骨髓快速动员至外周血。

研究设计与方法

为进一步研究AMD3100在CD34+细胞动员和采集方面的潜在临床应用,在正常志愿者中进行了一项I期研究,考察单独单次给予AMD3100以及与标准的5天粒细胞集落刺激因子(G-CSF)方案联合使用的情况。

结果

AMD3100(第5天给予160微克/千克×1次)显著提高了G-CSF刺激(10微克/千克/天)的CD34+细胞动员量(3.8倍)以及CD34+细胞的白细胞分离产量。此外,单剂量AMD3100方案(240微克/千克)动员的个体与5天G-CSF方案动员的个体之间,CD34+细胞的采集量相当。与G-CSF刺激的白细胞分离产物相比,AMD3100动员的白细胞分离产物中T细胞和B细胞数量显著更多。

结论

这些发现表明,AMD3100可单独使用或作为G-CSF的辅助药物用于动员细胞以进行HPC移植。

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