Neutrophil function is impaired in paediatric patients with malignancy and may be a useful clinical marker
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RESEARCH ARTICLE
Neutrophil function is impaired in paediatric patients with malignancy and may be a useful clinical marker J. Reiné1 · K. Cooper2 · A. Sewell2 · J. Lyall2 · C. Thorbinson2 · E. Hincks2 · D. M. Ferreira1 · B. Pizer2 · B. Morton1,3,4 Received: 29 February 2020 / Accepted: 28 April 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
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. Keywords Neutrophils · Biomarker · Paediatric cancer · Phagocytosis · Flow cytometry · Cytotoxic chemotherapy
Introduction Neutrophils defend against multiple pathogens relevant to patients with cancer including bacteria and fungi. Cytotoxic chemotherapy frequently causes neutropenia with resultant increased risk of infection. The incidence of neutropenic fever is influenced by underlying condition and Barry Pizer and Ben Morton Joint senior authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12094-020-02362-2) contains supplementary material, which is available to authorized users. * B. Morton [email protected] 1
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
2
Department of Paediatric Oncology, Alder Hey Children’s Hospital, Liverpool, UK
3
Lung Health Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
4
Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
both the nature and intensity of chemotherapy [1]. Bacteraemia is identified in 10–20% of neutropenic fever cases when blood cultures are taken [2]. There are currently no validated tools to predict which patients will develop neutropenic fever (neutrophil count is not adequately predictive unless ≤ 0.2 × 109/L) or bacteraemia. Current treatment algorithms advocate prophylactic antibiotic use for high-risk children to reduce the incidence of fever and hospitalisation after chemotherapy [3]. However, with
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