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Efficacy of the Granulocyte Colony-Stimulating Factor in Sepsis-Associated Immunosuppression: An Open-Label
K Keerthi Reddy1, Sunil Kumar Rao1, Anil Kumar Saroj1
1Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND.
Insights
Filgrastim (G-CSF) did not reduce mortality in children with sepsis-induced multi-organ failure syndrome (MOFS). This treatment was found to be safe but showed poor efficacy in reducing mortality or hospital-acquired infections.
Area of Science:
- Pediatric critical care medicine
- Hematology
- Immunology
Background:
- Sepsis-induced multi-organ failure syndrome (MOFS) in children is associated with high mortality.
- Granulocyte-colony stimulating factor (G-CSF), or filgrastim, is explored for its potential to mitigate organ dysfunction and mortality in critical illnesses.
Purpose of the Study:
- To evaluate the efficacy of filgrastim (G-CSF) in decreasing mortality among pediatric patients diagnosed with multi-organ failure syndrome (MOFS) persisting for at least three consecutive days.
- To assess the safety and impact of filgrastim on inflammatory biomarkers, hospital-acquired infections (HAI), and organ failure scores in this patient population.
Main Methods:
- A randomized controlled trial involving children aged 1 month to 18 years with MOFS (≥2 organ failures for 3 days) was conducted.
- Participants were randomized to receive either standard care plus filgrastim (4 mcg/kg/day subcutaneously for 7 days) or standard care alone.
- Blood samples were analyzed for inflammatory markers (TNF-α, ADAMTS13, FasL) to characterize sepsis-induced MOFS phenotypes.
Main Results:
- No significant difference in 28-day mortality was observed between the filgrastim group (27/39) and the control group (26/39) (p=0.81).
- Rates of hospital-acquired infection (HAI) and changes in pediatric sequential organ failure assessment (pSOFA) scores did not significantly differ between the groups.
- Filgrastim administration was safe, with no observed life-threatening adverse events or anaphylaxis.
Conclusions:
- Filgrastim (G-CSF) is safe for use in immunocompetent children experiencing sepsis-induced MOFS.
- A regimen of 2 doses of filgrastim over three days demonstrated poor efficacy in reducing mortality and did not significantly alter HAI frequency, TNF-α levels, or pSOFA scores.
Objective:
To determine the efficacy of filgrastim (G-CSF) in reducing the mortality in children with multi-organ failure syndrome (MOFS) persisting for three consecutive days. Methods: Children aged 1 month to 18 years with two or more organ failures persisting for three days according to Goldstein's criterion were included and randomized to receive either standard of care and filgrastim (G-CSF) at a dose of 4 mcg/kg/day subcutaneously for seven days or standard of care at a 1:1 ratio. The stored blood samples were estimated for TNF-α, A Disintegrin and Metalloproteinase Motifs 13 (ADAMTS13), and soluble Fas ligand (FasL) at the end of the study to confirm the biomarker-based inflammatory phenotypes of sepsis-induced MOFS. Outcomes were 28-day mortality and differences in tumor necrosis factor-alpha (TNF-α) levels, hospital-acquired infection (HAI), and pediatric sequential organ failure assessment score (pSOFA) at seven days of randomization.
Results:
Of 78 children, 25 (32%), 50 (64.1%), and 3 (3.8%) were discharged, died, and left against medical advice (LAMA), respectively. The two groups were similar except for a higher TLC (14100 [11400-16270]) vs. (17560 [13900-22100]; p=0.02) and male preponderance (18/39 vs. 27/39; p=0.03) in the control group. The intervention group received 2 (2-3) median (IQR) doses of filgrastim (G-CSF) for a 3 (2-3) median (IQR) duration of days. No significant difference was observed between the groups regarding 28-day mortality (26/39 vs. 27/39; 95% CI, p (0.71-1.31, p=0.81), HAI (31/62 vs. 21/53; p=0.27). The pSOFA scores and TNF-α levels at seven days were 8 (6-12) vs. 9 (8-11) (p=0.12) and 81.6 (6.9-237.2) vs. 99.6 (16.2-404.2) (p=0.29), respectively. Subgroup analysis revealed a similar occurrence of mortality in immunoparalysis-associated multi-organ failure (IPMOF) (16/26 vs. 14/21); 95% CI, p (0.60-1.42, p=0.71) at 28 days, and 2 median dose of filgrastim (G-CSF) for 3 median day did not significantly change the TNF-α levels within the intervention group at day seven (56 [32-118] vs. 19 [6.9-118], p=0.77) as compared to day 0. We did not observe any life-threatening/significant sudden deterioration/anaphylaxis after use of filgrastim (G-CSF).
Conclusions:
Filgrastim (G-CSF) use in immunocompetent children with sepsis-induced MOFS is safe, and a 2-dose of filgrastim (G-CSF) for three days has poor efficacy in the reduction of mortality and did not show significant change in frequency of HAI, TNF-α levels, and pSOFA scores.
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