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中性粒细胞减少症和非格司亭(G-CSF)对感染 2019 冠状病毒病(COVID-19)的癌症患者的影响。

The Effect of Neutropenia and Filgrastim (G-CSF) on Cancer Patients With Coronavirus Disease 2019 (COVID-19) Infection.

机构信息

MD/PhD Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Infectious Disease, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

出版信息

Clin Infect Dis. 2022 Mar 1;74(4):567-574. doi: 10.1093/cid/ciab534.

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.

摘要

背景

中性粒细胞减少症在癌症患者中很常见。重组人粒细胞集落刺激因子(G-CSF,非格司亭)是一种细胞因子,可启动成熟粒细胞的增殖和分化,广泛用于肿瘤患者以对抗中性粒细胞减少症,降低感染易感性。然而,中性粒细胞减少症和 G-CSF 在患有 2019 年冠状病毒病(COVID-19)的癌症患者中的临床影响尚不清楚。

方法

我们组建了一个由 379 名患有 COVID-19 的积极治疗的癌症患者组成的观察性队列,以研究同时发生的中性粒细胞减少症和 G-CSF 给药与 COVID-19 相关呼吸衰竭和死亡之间的关系。这些因素在扩展的 Cox 模型中被编码为时间依赖性预测因子,同时控制年龄和基础癌症诊断。为了确定粒细胞对 G-CSF 的反应程度是否影响结局,我们还将基于生长因子给药后 24 小时绝对中性粒细胞计数(ANC)升高的 G-CSF 反应程度纳入类似的 Cox 模型。

结果

在 COVID-19 感染活跃的情况下,门诊接受 G-CSF 治疗会导致住院次数增加(风险比 [HR]:3.54,95%置信区间 [CI]:1.25-10.0,P 值:.017)。此外,在住院患者中,G-CSF 给药与需要更高水平的氧补充和死亡相关(HR:3.56,95% CI:1.19-10.2,P 值:.024)。这种作用主要见于 G-CSF 给药后 ANC 升高的患者(HR:7.78,95% CI:2.05-27.9,P 值:.004)。

结论

对于患有 COVID-19 的中性粒细胞减少症癌症患者,应考虑 G-CSF 给药的潜在风险与获益,因为 G-CSF 给药可能导致临床和呼吸状况恶化。

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