The Effect of Neutropenia and Filgrastim (G-CSF) in Cancer Patients With COVID-19 Infection

中性粒细胞减少症和非格司亭(G-CSF)对合并 COVID-19 感染的癌症患者的影响

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Abstract

BACKGROUND: Neutropenia is commonly encountered in cancer patients, and recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) is widely given to oncology patients to counteract neutropenia and prevent infection. G-CSF is both a growth factor and cytokine that initiates proliferation and differentiation of mature granulocytes. However, the clinical impact of neutropenia and G-CSF use in cancer patients, who are also afflicted with coronavirus disease 2019 (COVID-19), remains unknown. METHODS: An observational cohort of 304 hospitalized patients with COVID-19 at Memorial Sloan Kettering Cancer Center was assembled to investigate links between concurrent neutropenia (N=55) and G-CSF administration (N=16) on COVID-19-associated respiratory failure and death. These factors were assessed as time-dependent predictors using an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, a similar model was constructed with patients that received G-CSF, categorized into high- and low-response, based on the level of absolute neutrophil count (ANC) rise 24 hours after growth factor administration. RESULTS: Neutropenia (ANC < 1 K/mcL) during COVID-19 course was not independently associated with severe respiratory failure or death (HR: 0.71, 95% Cl: 0.34-1.50, P value: 0.367) in hospitalized COVID-19 patients. When controlling for neutropenia, G-CSF administration was associated with increased need for high oxygen supplementation and death (HR: 2.97, 95% CI: 1.06-8.28, P value: 0.038). 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: 5.18, 95% CI: 1.61-16.64, P value: 0.006). CONCLUSION: Possible risks versus benefits of G-CSF administration should be weighed in neutropenic cancer patients with COVID-19 infection, as G-CSF may lead to worsening clinical and respiratory status in this setting.

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