Meister B, Maurer H, Simma B, Kern H, Ulmer H, Hittmair A, Fink F M
Department of Pediatrics, University of Innsbruck, Austria.
Stem Cells. 1997;15(5):359-63. doi: 10.1002/stem.150359.
In vitro and animal studies suggest that high concentrations of recombinant human erythropoietin (rHuEPO) might divert multipotent progenitors into erythroid maturation at the expense of granulocyte production. We determined whether changes of number and lineage commitment of peripheral blood progenitor cells occur in premature infants during therapy with rHuEPO. Thirty preterm infants were randomly assigned either to receive 300 IU of eopoetin alpha s.c. per kilogram body weight three times a week for four weeks or to a control group. At study entry and after two weeks of treatment the numbers of circulating BFU-E, granulocyte-macrophage colony-forming units (CFU-GM) and granulocyte-erythrocyte-macrophage-megakaryocyte CFU (CFU-GEMM) were analyzed by semisolid culture technique, CD34+ cells and early myeloid CD34+CD45RA- progenitors by flow cytometry. As compared with the control group, rHuEPO treatment did not exert any significant modulatory effect on numbers of CFU-GM, nor was there a significant change in numbers of BFU-E, CFU-GEMM, total-CFU, percentage of CD34+ or CD34+CD45RA- cells. Mean neutrophil count was not significantly reduced at any period during the study. Compared with the control group, the infants receiving rHuEPO had higher hematocrit values (p = 0.003) and absolute reticulocyte counts (p < 0.001). The median cumulative volume of blood transfused per kilogram per day was 0.86 ml (first quartile 0.5 ml; third quartile 1.1 ml) in the control group and 0 ml (first quartile 0 ml; third quartile 0.47 ml) in the rHuEPO group (p = 0.038). We conclude using a relatively high dose of rHuEPO in premature infants, no significant in vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected.
体外和动物研究动物研究表明，高浓度的重组人促红细胞生成素（rHuEPO）可能会使多能祖细胞转向红系成熟，而以粒细胞生成受损为代价。我们确定了在早产儿接受rHuEPO治疗期间，外周血祖细胞数量和谱系定向是否发生变化。30名早产儿被随机分为两组，一组每周皮下注射300国际单位每千克体重的α-促红细胞生成素，共四周，另一组为对照组。在研究开始时和治疗两周后，通过半固体培养技术分析循环中的爆式红系集落形成单位（BFU-E）、粒细胞-巨噬细胞集落形成单位（CFU-GM）和粒细胞-红细胞-巨噬细胞-巨核细胞集落形成单位（CFU-GEMM）数量，通过流式细胞术分析CD34+细胞和早期髓系CD34+CD45RA-祖细胞数量。与对照组相比，rHuEPO治疗对CFU-GM数量没有显著调节作用，BFU-E、CFU-GEMM、总集落形成单位（total-CFU）数量、CD34+或CD34+CD45RA-细胞百分比也没有显著变化。在研究期间的任何时间段，平均中性粒细胞计数均未显著降低。与对照组相比，接受rHuEPO治疗的婴儿有更高的血细胞比容值（p = 0.003）和绝对网织红细胞计数（p < 0.001）。对照组每千克每天输血的累积中位数体积为0.86毫升（第一四分位数0.5毫升；第三四分位数1.1毫升），rHuEPO组为0毫升（第一四分位数0毫升；第三四分位数0.47毫升）（p = 0.038）。我们得出结论，在早产儿中使用相对高剂量的rHuEPO，未检测到对循环外周血祖细胞或中性粒细胞计数有显著的体内效应。
