Search for novel biomarkers of febrile neutropenia in hematological patients: an overview

A single-center prospective study was conducted at a tertiary care hospital in Kuopio Finland over the past two decades, searching for novel biomarker candidates to predict complicated course of febrile neutropenia (FN) in hematological patients. In Dec 2006‒Dec 2015, 85 patients with acute myeloid leukemia and 179 autologous hematopoietic stem cell transplant recipients were included. More than 20 biomarkers were evaluated in subsequent patient cohorts and compared to C-reactive protein (CRP) and procalcitonin (PCT). The samples were taken on d0-d2 from the beginning of FN. Here, we provide an overview of the results of these studies. Most biomarkers evaluated did not provide additional prognostic benefit compared to CRP or PCT. The most promising biomarkers warranting further studies include soluble cluster of differentiation 14, interleukin-1-receptor antagonist, interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and caspase-cleaved cytokeratin-18. Several biomarkers evaluated in this series of studies are hampered by impaired production by neutrophils/leukocytes (matrix metalloproteinase-8, cell-free plasma DNA and soluble urokinase plasminogen activator receptor) or platelets (vascular endothelial growth factor). For now, these novel biomarkers cannot substitute the conventional markers nor provide additional benefit in routine use. Optimally, the most promising novel markers should be evaluated in prospective multicenter studies with higher patient numbers and several endpoints to more reliably evaluate their performance. At present, close patient monitoring is imperative in hematological patients with FN. The additional information provided by novel FN biomarkers may be useful, but they should be evaluated combined with daily evaluation of sepsis scoring systems.