Intensive Serial Biomarker Profiling for the Prediction of Neutropenic Fever in Patients with Hematologic Malignancies Undergoing Chemotherapy: A Pilot Study

Neutropenic fever (NF) is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial measurements of nine biomarkers [C-reactive protein (CRP), protein C, interleukin (IL)-6, IL-8, IL-10, IL-1β, tumor necrosis factor-α, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793).