Schibler K R, Osborne K A, Leung L Y, Le T V, Baker S I, Thompson D D
Department of Pediatrics, Division of Neonatology, and the Clinical Research Center, University of Utah School of Medicine, Salt Lake City, Utah 34132, USA.
Pediatrics. 1998 Jul;102(1 Pt 1):6-13. doi: 10.1542/peds.102.1.6.
To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis.
We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded.
Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality.
Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.
确定重组人粒细胞集落刺激因子（G-CSF）给药是否：1）加速中性粒细胞的生成；2）增加骨髓储存的和前体中性粒细胞；3）对患有中性粒细胞减少症且有早发型败血症临床体征的新生儿是安全的。
我们将出生后前3天患有中性粒细胞减少症且有早发型败血症临床体征的20名婴儿随机分为两组，一组接受G-CSF（10微克/千克/天）治疗3天，另一组接受安慰剂治疗3天。入选标准包括根据门罗标准定义的中性粒细胞减少症、未成熟与总中性粒细胞比值升高[（I/T）≥0.25]以及需要通气支持。对所有研究婴儿进行培养并开始使用抗生素。评估循环中的绝对中性粒细胞计数（ANC）、I/T比值、骨髓中性粒细胞储存池（NSP）和中性粒细胞增殖池（NPP）以及血浆G-CSF浓度。此外，记录使用新生儿急性生理学评分（SNAP）确定的疾病严重程度、发病率和死亡率。
到第1天时，G-CSF组和安慰剂组的循环ANC均增加。同样，G-CSF组和安慰剂组的中性粒细胞I/T比值均下降。在研究期间，两组之间的ANC或I/T比值没有显著差异。同样，在研究开始时或第2天，G-CSF组和安慰剂组的骨髓NSP和NPP没有差异。在包括疾病严重程度、发病率和死亡率在内的次要结局指标中未观察到差异。
与安慰剂相比，给患有中性粒细胞减少症且有早发型败血症临床体征的婴儿注射重组G-CSF并未增加循环ANC、骨髓NSP和NPP。在疾病严重程度、发病率或死亡率方面，G-CSF组和安慰剂组之间未观察到差异。未注意到G-CSF给药的不良反应。
