Human Granulocyte Colony-stimulating Factor May Improve Outcome Attributable to Neonatal Sepsis Complicated by Neutropenia

Abstract

ABSTRACT. Objectives. To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I/II-type trial.Study Design. An intravenous infusion of rhG-CSF (10 g/kg/d ؋ 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia ( 24 hours).Results. Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean ؎ SEM) was 585 ؎ 138 and 438 ؎ 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or platelet counts was noted. Thirteen patients in the rhG-CSF-treated group (92%; 13 out of 14) and five in the conventionally treated group (55%; 5 out of 11) survived to 28 days after the onset of the signs of sepsis. No adverse effects were noted in the rhG-CSF-treated group.Conclusions. rhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonates. This finding suggests that rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow suppression or neutrophil consumption. Future randomized trials are needed to validate the beneficial effects of rhG-CSF and to determine whether any significant side effects of therapy exist. Pediatrics 1997;100(1). URL: http: //www.pediatrics.org/cgi/content/full/100/1/e6; neonatal sepsis, recombinant human granulocyte colony stimulating factor, bacteremia, cytokines, very low birth weight, neutropenia.

Neonatal Alloimmune Neutropenia

“…However, evidence on effectiveness is lacking. Treatment with G-CSF is highly effective in increasing neutrophil numbers within days in a majority of cases and can be considered especially for neonates suffering from severe infections [60,61,62]. One should keep in mind that resistance to G-CSF in NAIN associated with anti-HNA-2 antibodies, possibly due to a G-CSF-induced increase of HNA-2 expression on the neutrophils, has been described [63,64,65].…”

A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor

“…G-CSF is also being used clinically to facilitate hematopoietic recovery after bone marrow transplantation, to mobilize peripheral blood progenitor cells in healthy donors, and to treat severe congenital neutropenia. [32][33][34][35] Available data suggest that there is little doubt that G-CSF is a safe agent for use in the human population.…”

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

“…In 14 neutropenic infants with sepsis (seven with early-onset sepsis and seven with NEC), G-CSF therapy was associated with a relatively higher WBC count and improved survival. 52 Over 250 infants have been enrolled in controlled clinical trials treating early-and late-onset sepsis, including NEC, with G-CSF, summarized by Kocherlakota and La Gamma. 52 Although C-CSF was safe and WBC increased, no improvement in survival was seen.…”

“…52 Over 250 infants have been enrolled in controlled clinical trials treating early-and late-onset sepsis, including NEC, with G-CSF, summarized by Kocherlakota and La Gamma. 52 Although C-CSF was safe and WBC increased, no improvement in survival was seen. In a recent meta-analysis of randomized and nonrandomized controlled studies of G-CSF therapy in neonatal sepsis, G-CSF was associated with improved survival, especially when accompanied by neutropenia.…”