Abstract
Background: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown.
Methods: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model.
Results: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004).
Conclusions: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status.
Keywords: COVID-19; cancer; granulocyte colony stimulating factor; neutropenia.
【저자키워드】 COVID-19, Cancer, neutropenia, granulocyte colony stimulating factor, 【초록키워드】 coronavirus disease, Respiratory failure, Hospitalization, susceptibility, Infection, cytokine, outcomes, Cohort, COVID-19 infection, Patient, Cancer patients, death, clinical impact, age, predictor, neutropenia, administration, recombinant, cancer patient, proliferation, granulocyte, Inpatients, Factor, 95% confidence interval, hazard ratio, worsening, potential risk, G-CSF, growth factor, absolute neutrophil count, oxygen supplementation, cancer diagnosis, benefit, Cox model, affected, exhibited, treated, determine, reducing, initiate, 24 hour, ANC, oncology patient, with COVID-19, 【제목키워드】 G-CSF, filgrastim, Effect,