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

  1. Allen W Zhang
  2. Sejal Morjaria
  3. Anna Kaltsas
  4. Tobias M Hohl
  5. Rekha Parameswaran
  6. Dhruvkumar Patel
  7. Wei Zhou
  8. Jacqueline Predmore
  9. Rocio Perez-Johnston
  10. Justin Jee
  11. Anthony F Daniyan
  12. Miguel-Angel Perales
  13. Ying Taur

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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.

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  1. Version published to 10.1093/cid/ciab534
  2. ScreenIT

    SciScore for 10.1101/2020.08.13.20174565: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The Memorial Sloan Kettering Cancer Center (MSKCC) institutional review board approved the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study is not without its limitations. The study ultimately included a modest number of patients receiving G-CSF (N=16). In this observational cohort, unaccounted confounding factors are plausible. This analysis attempted to assess G-CSF over a wide range of cancers; tumor-specific effects were difficult to ascertain. We also limit our primary analysis to the subset of patients who were hospitalized, to be able to assess our clinical endpoints of interest (respiratory failure or death). As a result, the potential for G-CSF to worsen outcomes, suggested here, may not be generalizable to outpatients. While our analysis adjusts for the neutrophil count prior to G-CSF administration, we have not incorporated data on concurrent therapies such as chemotherapies or surgery prior to the diagnosis of COVID-19 in these patients. Interestingly, in lieu of the COVID-19 pandemic, the National Comprehensive Cancer Network and the American Society of Clinical Oncology have released updated guidelines on this very issue, lowering the threshold for the use of G-CSF to now include those chemotherapy regimens that carry a 10 to 20 percent risk of fever in the setting of neutropenia24. Although there is a potential role for G-CSF and its prophylactic use following the administration of chemotherapy when neutropenia is anticipated (primary prophylaxis) and during retreatment after a previous cycle of chemotherapy had caused fever during neutropenia (secondary prophylaxis),25 G-CSF has not def...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.08.13.20174565v1 on medRxiv