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Neutrophil function is impaired in paediatric patients with malignancy and may be a useful clinical marker

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Abstract

Purpose

Patients treated with cytotoxic chemotherapy are at risk of neutropenia, neutropenic fever and neutropenic sepsis. We hypothesised that pre-existing neutrophil function dysfunction may increase susceptibility to neutropenic fever in paediatric patients receiving cytotoxic chemotherapy.

Methods

Prospective cohort study recruited patients at Alder Hey Children’s NHS Foundation Trust, United Kingdom. We measured neutrophil phagocytic function using a validated flow cytometric whole blood phagocytosis assay in paediatric patients (n = 16) with oncological disease before and after chemotherapy in a prospective cohort study. We recruited healthy children as a control comparator (n = 10).

Results

We found significantly decreased phagocytic function in oncology patients compared to healthy participants. In five patients who developed neutropenic fever, we observed increased pre-dose neutrophil respiratory burst.

Conclusion

With further validation, measurement of neutrophil function could potentially be used to personalise appropriate prophylactic antimicrobial administration for patients receiving cytotoxic chemotherapy.

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Data availability

The dataset supporting the conclusions of this article is included within the article (and its additional files).

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Funding

This work was supported by the Amy Laura Fund and Alder Hey Charity (Reference 8538) awared to BP. Flow cytometry acquisition was performed on a BD LSR II cytometer funded by a (104936/Z/14/Z). B.M. thanks the NIHR Global Health Research Unit on Lung Health and TB in Africa at LSTM—“IMPALA” for helping to make this work possible by part funding Dr. Morton’s academic salary during the conduct of this study. In relation to IMPALA (grant number 16/136/35) specifically: IMPALA was commissioned by the National Institute of Health Research using Official Development Assistance (ODA) funding. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

Author information

Authors and Affiliations

  1. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK

    J. Reiné, D. M. Ferreira & B. Morton

  2. Department of Paediatric Oncology, Alder Hey Children’s Hospital, Liverpool, UK

    K. Cooper, A. Sewell, J. Lyall, C. Thorbinson, E. Hincks & B. Pizer

  3. Lung Health Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi

    B. Morton

  4. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK

    B. Morton

Authors
  1. J. Reiné
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  2. K. Cooper
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  3. A. Sewell
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  4. J. Lyall
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  5. C. Thorbinson
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  6. E. Hincks
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  7. D. M. Ferreira
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  8. B. Pizer
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  9. B. Morton
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Contributions

JR, DF, BM and BP contributed to conceiving, designing, performing and analysing experiments and writing of the paper. JR, KC, AS, EH, DF, BM and BP contributed to conducting and analysing experiments. JR, KC, AS, EH, DF, BM and BP contributed to sample collection and/or design of the study. JR, BM and PF contributed to conceiving and analysing the study and experiments. All authors have read and approved the manuscript.

Corresponding author

Correspondence to B. Morton.

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Conflict of interest

The authors declare no competing interests.

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London Bridge Research Ethics Committee (17/LO/1625).

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All authors have reviewed the manuscript and consent to publication.

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Barry Pizer and Ben Morton Joint senior authors.

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Reiné, J., Cooper, K., Sewell, A. et al. Neutrophil function is impaired in paediatric patients with malignancy and may be a useful clinical marker. Clin Transl Oncol 22, 2121–2125 (2020). https://doi.org/10.1007/s12094-020-02362-2

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  • DOI: https://doi.org/10.1007/s12094-020-02362-2

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