G-CSF ADMINISTRATION TO NEONATES WITH EARLY-ONSET SEPSIS AND NEUTROPENIA: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL. ▴ 1730

Abstract

Our laboratory has previously reported diminished granulocyte colony-stimulating factor (G-CSF) production in vitro and in vivo by human neonates and normal responsiveness of neonatal hematopoietic progenitors to recombinant G-CSF. We sought to determine whether G-CSF administration would enhance neutrophil production and recovery from illness in neonates with early-onset bacterial sepsis and neutropenia. Infants 0.5, requiring ventilatory support, and being treated for suspected sepsis, were randomized in double-blinded fashion to receive G-CSF (10 mcg/kg) or placebo IV daily for three days. CBC's, cytokine levels, and clinical status were monitored. Gestational age, weight, and gender were similar in both groups. Neutrophil counts increased fourfold in G-CSF-treated (p<0.05 vs baseline) and twofold in placebo-treated infants (N.S.) by 24 hours. Endogenous G-CSF concentration in plasma was 3889±2253 (X±s.d.) at entry, however, four preterm infants exhibited low levels of G-CSF despite significant neutropenia. Severity of illness was greater in G-CSF-treated infants at entry, 30±13 vs 24±12 (X±s.d.) as determined by Score for Acute Neonatal Physiology-Perinatal Extension (SNAP-PE), however, the rate of recovery was not significantly different between groups. Mortality was lower in G-CSF-treated infants than predicted by initial SNAP-PE (20% actual vs 26% predicted), but higher than predicted in placebo-treated infants(30% vs 13%). All five VLBW infants (≤ 28 weeks GA) receiving G-CSF survived vs two of four placebo-treated VLBW infants. Morbidity associated with prematurity was higher in the G-CSF- than in the placebo-treated cohort. In summary G-CSF shortened the duration of neutropenia, but it did not alter the rate of recovery from acute infection. A multicenter trial is in progress to determine the efficacy of G-CSF in treatment of neonates with sepsis and neutropenia.