Elsevier

Cytokine

Volume 62, Issue 1, April 2013, Pages 34-37
Cytokine

Short Communication
The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia

https://doi.org/10.1016/j.cyto.2013.02.030Get rights and content

Abstract

Background

Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients.

Methods

A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups.

Results

Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently.

Conclusions

PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia.

Highlights

► We investigated infectious complications in febrile neutropenia oncology patients. ► PCT, IL-2R were used as the markers of bacteremia/sepsis (BS) determination. ► PCT, IL-2R might be used as an additional diagnostic tool for the detection of BS.

Introduction

Chemotherapy-related febrile neutropenia (FN) is a frequent complication in children with cancer. Neutropenia is a major risk factor for infection in these patients. Among children with FN, the main symptom of infection upon initial presentation may be fever only. Therefore, a standard approach for these patients includes immediate hospitalization, empirical treatment with intravenous broad-spectrum antibiotics until they become afebrile and neutrophil count has recovered [1]. However, in only 20–30% of children with FN a bacterial infection is determined, which results in overtreatment of these patients with consequent increasing risk of bacterial resistance development [2]. Therefore, biomarkers having the potential to predict infectious process in FN cancer patients are of great interest.

To date, there have been many studies performed in FN patients, which assessed various inflammation-related biomarkers in terms of prediction of severe infection [1], [3], however, due to a heterogeneity between the studies, limited data describing the predictive value of different biomarkers is available [4].

CD14 is a cell surface glycoprotein, which is constitutively expressed in a majority of innate immune response cells and exists either in an anchored membrane form, or in a soluble form (sCD14-ST, presepsin). It was shown that sCD14-ST levels increase during sepsis and systemic inflammatory response syndrome [5].

Human leucocyte antigen-G (HLA-G) is non-classical HLA class Ib molecule, which is upregulated in various tumors and exerts immunoregulatory effects. An immune suppressive action of soluble HLA-G (sHLA-G) on immune system cells has been documented [6]. The predictive value of sHLA-G, as well as sCD14-ST for the presence of bacteremia/sepsis is questionable, because these markers have not been evaluated in neutropenic oncology patients before.

Procalcitonin (PCT) is a 116 amino acid peptide that is normally produced by thyroid C cells in response to hypercalcemia. Bacterial infection triggers PCT production in parenchymal cells throughout the body and as a consequence, PCT levels increase very quickly after the onset of infection. Therefore, PCT was suggested as a marker of infection [1], [7].

Interleukin-2 (IL-2) is one of the mediators of immunity and inflammation and it was shown that soluble IL-2 receptors (sIL-2R) have inhibitory effect on immune response [8].

The aim of this study was to assess the predictive value of the above-mentioned biomarkers in the identification of bacteremia/sepsis at the beginning of a febrile episode in childhood cancer patients.

Section snippets

Patient characteristics

This study was performed at the Department of Oncohematology at Vilnius University Children Hospital. Plasma samples were collected during each febrile neutropenic episode at presentation. Informed consent, after verbal and written information provision, was obtained from all patients. Permission for this study was provided by the Regional Committee of Bioethics.

Neutropenia was defined as an absolute neutrophil count (ANC) less than 0.5 × 109/l at the onset of fever. Fever was defined as a single

Demographic data

A total of 62 FN episodes in 37 patients including acute lymphoblastic leukemia (n = 28), acute myeloblastic leukemia (n = 2), non-Hodgkin’s lymphoma (n = 1) and non-hematologic malignancies (osteosarcoma (n = 3), medulloblastoma, nephrosarcoma, neuroblastoma) were enrolled in this study. 12 patients were enrolled more than once. Duration of febrile episodes in FUO group was 1–11 days (median 2 days) and in BS group was 1–18 days (median 2 days). There were 13 females and 24 males with a median age of 6 

Discussion

In this study we explored the value of biomarkers as a diagnostic tool of bacteremia/sepsis at the beginning of FN in pediatric oncology patients. We showed that PCT and sIL-2R might be used as an additional diagnostic tool for the evaluation of bacteremia/sepsis at the beginning of FN.

Hatzistilianou and colleagues [9] showed that PCT might be useful for the early prediction of bacterial infections. Other studies revealed that PCT alone or in combination with other markers was helpful for the

Conflict of interest

This study was partially funded by the Lithuanian Foundation of Sciences and Studies Research Grant.

Acknowledgment

The authors thank to Natalija Drapeko for excellent laboratory assistance.

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