Research Article Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics Marika Lappalainen, 1,2 Jenna Jokkala, 3 Auni Juutilainen, 2 Sari Hämäläinen, 4 Irma Koivula, 4 Esa Jantunen, 2,4,5 Kati Hanhineva, 3 and Kari Pulkki 6,7,8 1 Department of Internal Medicine, Central Hospital of Central Finland, Jyväskylä, Finland 2 Institute of Clinical Medicine/Internal Medicine, University of Eastern Finland, Kuopio, Finland 3 Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland 4 Department of Medicine, Kuopio University Hospital, Kuopio, Finland 5 Siun Sote-Hospital District of North Carelia, Joensuu, Finland 6 Eastern Finland Laboratory Centre, Kuopio, Finland 7 Laboratory Division, Turku University Hospital, Turku, Finland 8 Clinical Chemistry, Faculty of Medicine, University of Turku, Turku, Finland Correspondence should be addressed to Kari Pulkki; kari.pulkki@utu.fi Received 3 November 2017; Revised 4 February 2018; Accepted 22 February 2018; Published 12 April 2018 Academic Editor: Hyundoo Hwang Copyright © 2018 Marika Lappalainen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies. Methods. Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38 ° and on the next morning. Results. Altogether, 90 differential molecular features were shown to explain the differences between patients with complicated (bacteremia, severe sepsis, or fatal outcome) and noncomplicated courses of febrile neutropenia. The most differential compounds were an androgen hormone, citrulline, and phosphatidylethanolamine PE(18:0/20:4). The clinical relevance of the findings was evaluated by comparing them with conventional biomarkers like C-reactive protein and procalcitonin. Conclusion. These results hold promise to find out novel biomarkers for febrile neutropenia, including citrulline. Furthermore, androgen metabolism merits further studies. 1. Introduction Febrile neutropenia is a common complication in hemato- logical patients receiving intensive chemotherapy. Although a minority of these patients develop septic shock [1, 2], sepsis is still a major cause of morbidity and mortality during the neutropenic phase [3, 4]. In these patients, life-threatening complications can develop in hours depending on the patho- gen. Not only C-reactive protein (CRP) and procalcitonin (PCT) but also several other biomarkers have been explored to identify patients at risk for complicated course of febrile neutropenia [5]. CRP and PCT both have some limitations such as nonspecificity and delayed response. PCT is superior to CRP for predictive purposes and is slightly more pathogen- dependent, especially in gram-negative bacteremia [3, 6]. However, there still is a need for more rapid and accurate markers, which also could be used for de-escalation strategies of broad-spectrum antibiotics. Nontargeted metabolite profiling or metabolomics is a hypothesis-free study approach that focuses on finding differ- ences in metabolite profiles between study subjects contribut- ing to the discovery of novel small-sized molecular biomarkers for disease progression or prevention [7, 8]. In previous studies, metabolomics has been used to differentiate sepsis Hindawi Disease Markers Volume 2018, Article ID 6964529, 16 pages https://doi.org/10.1155/2018/6964529