Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
Cytotherapy. 2009;11(8):992-1001. doi: 10.3109/14653240903121245.
Previous studies in xenograft models have shown that human peripheral blood progenitor cells (PBPC) mobilized with the CXCR4 antagonist plerixafor (AMD3100) have a higher bone marrow (BM) reconstitution potential than granulocyte-colony-stimulating factor (G-CSF)-mobilized PBPC.
PBPC obtained during G-CSF-supported mobilization before and after a supplementary administration of AMD3100 from patients with multiple myeloma and non-Hodgkin's lymphoma (n=15; phase II study) were investigated for co-expression of primitive and lineage-associated markers, their proliferative activity in vitro and repopulation potential after clinical transplantation.
A significant increase in primitive CD34+ CD38(-) cells was observed in intraindividual comparisons of all patients after administration of G-CSF+AMD3100 (peripheral blood: median 8-fold, range 2,4-fold - 39-fold) compared with G-CSF alone. Using a long-term culture-initiating cell assay, this increase was confirmed. After transplantation of G-CSF+AMD3100-mobilized PBPC, the time to leukocyte reconstitution > 1 x 10(3)/microL and platelet reconstitution > 2 x 10(4)/microL was 14 (10-19 days) and 13 days (10-15 days), respectively. A complete and stable hematologic reconstitution (platelets > 1.5 x 10(5)/microL) was observed in 91% of all patients within 35 days.
An additional application of AMD3100 to a standard G-CSF mobilization regimen leads to a significant increase in primitive PBPC with high repopulation capacity.
先前的异种移植模型研究表明，与粒细胞集落刺激因子（G-CSF）动员的外周血祖细胞（PBPC）相比，使用趋化因子受体 4 拮抗剂plerixafor（AMD3100）动员的人外周血祖细胞（PBPC）具有更高的骨髓（BM）重建潜力。
研究了多发性骨髓瘤和非霍奇金淋巴瘤患者在 G-CSF 支持动员前后，以及补充 AMD3100 后（n=15；II 期研究）获得的 PBPC，检测其原始和谱系相关标记物的共表达、体外增殖活性以及临床移植后的再群体潜力。
与单独使用 G-CSF 相比，所有患者的个体内比较均观察到 G-CSF+AMD3100 给药后原始 CD34+ CD38(-)细胞明显增加（外周血：中位数 8 倍，范围 2 至 39 倍）。使用长期培养起始细胞测定法，证实了这种增加。在移植 G-CSF+AMD3100 动员的 PBPC 后，白细胞重建>1 x 10(3)/µL 和血小板重建>2 x 10(4)/µL 的时间分别为 14 天（10-19 天）和 13 天（10-15 天）。所有患者中有 91%在 35 天内观察到完全和稳定的血液重建（血小板>1.5 x 10(5)/µL）。
在标准 G-CSF 动员方案中额外应用 AMD3100 可显著增加具有高重建能力的原始 PBPC。
