Medizinische Klinik und Poliklinik I, University Hospital, Dresden, Germany.
Biol Blood Marrow Transplant. 2013 Oct;19(10):1517-21. doi: 10.1016/j.bbmt.2013.07.018. Epub 2013 Jul 23.
Analyses of healthy donors of granulocyte colony-stimulating factor (G-CSF) mobilized hematopoietic stem and progenitor cells (HSPCs) and of patients undergoing autologous stem cell transplantation have suggested that individuals harboring the CXCL12-A allele mobilize a higher number of CD34 + HSPCs after G-CSF administration. We typed 463 healthy unrelated donors (376 men and 87 women) who had received daily subcutaneous injections at a mean dose of 7.36 ± 1.71 μg/kg G-CSF for 5 days for CXCL12 801 G/A using a real-time PCR assay. Interestingly, the median concentration of mobilized CD34 + cells on day 5 was almost identical in donors with the A-allele (79/μL; range, 11 to 249/μL) and the G/G-group (82/μL; range, 15 to 268/μL). In addition, the allelic distribution was not different in donors (n = 11) who mobilized less than 20/μL CD34 + cells. No difference in the overall yield of CD34 + cells in the apheresis product and in the number of CD34 + cells/kg recipient could be detected between both groups. In a multivariate regression model for the endpoint CD34 + cells/μL at day 5, only male sex (regression coefficient, 11.5; 95% confidence interval, 1.7 to 21.2, P = .021) and body mass index as continuous variables (regression coefficient, 3.5; 95% confidence interval, 2.5 to 4.5, P = .0001) but not age, smoking status, or CXCL12 allelic status represented independent variables. Our data derived from a large well-controlled cohort contradict previous analyses suggesting an association between CXCL12 allelic status and the yield of CD34 + HSPC after G-CSF mobilization. Concentration of CD34 + cells in the peripheral blood, the most objective parameter, could not be predicted by CXCL12 genotype.
对粒细胞集落刺激因子(G-CSF)动员造血干细胞和祖细胞(HSPC)的健康供体和接受自体干细胞移植的患者进行的分析表明,携带 CXCL12-A 等位基因的个体在用 G-CSF 治疗后动员更多的 CD34+HSPC。我们使用实时 PCR 分析对 463 名健康的无关供体(376 名男性和 87 名女性)进行了 CXCL12 801 G/A 分型,这些供体在 5 天内每天接受皮下注射平均剂量为 7.36±1.71μg/kg G-CSF。有趣的是,第 5 天动员的 CD34+细胞的中位数浓度在 A 等位基因(79/μL;范围,11 至 249/μL)和 G/G 组(82/μL;范围,15 至 268/μL)中几乎相同。此外,在动员 CD34+细胞<20/μL 的供体(n=11)中,等位基因分布无差异。在两个组之间,无法检测到在单采产品中的 CD34+细胞的总体产量和 CD34+细胞/kg 受者数量之间存在差异。在针对第 5 天 CD34+细胞/μL 终点的多变量回归模型中,只有男性(回归系数,11.5;95%置信区间,1.7 至 21.2,P=0.021)和体重指数作为连续变量(回归系数,3.5;95%置信区间,2.5 至 4.5,P=0.0001),而不是年龄、吸烟状况或 CXCL12 等位基因状态作为独立变量。我们的数据来自一个大型的、经过严格控制的队列,与之前的分析结果相矛盾,该分析结果表明 CXCL12 等位基因状态与 G-CSF 动员后 CD34+HSPC 的产量之间存在关联。外周血中 CD34+细胞的浓度,作为最客观的参数,不能通过 CXCL12 基因型预测。