Biomarkers were assessed during neutropenic fever in hematopoietic stem cell transplantation (HSCT). The objective was to assess serum values of C-reactive protein (CRP), procalcitonin (PCT) and IL-6 to identify infection in HSCT and risk factors for death.
Materials and methods
Prospective study with 296 patients submitted to autologous or allogeneic HSCT. PCT, CRP and IL-6 dosed at the following moments: afebrile neutropenia, fever, 24 hours upon fever, 72 hours upon fever and long-lasting fever. Patients were classified into groups (I, afebrile; II, fever of unknown origin; and III, clinically or microbiologically proven fever). ROC curves, sensitivity, specificity, and multivariate analysis were used to evaluate factors associated with death.
One hundred and ninety patients had fever. Mean and median values of IL-6 at fever onset in group I with regard to group II (P = 0.013) presented significantly higher values. Levels of CRP in group I differed significantly from those found in group III (P < 0.05). Groups differed in levels of IL-6 and CRP at fever onset. Group II presented IL-6 and CRP concentrations significantly lower than group III. Cutoff values of PCT: fever onset, 24 hours upon fever, 72 hours of fever, and long-standing fever were: 0.32; 0.47; 0.46 and 0.35 µg/l. At fever onset, sensitivity was 52.3 and specificity 52.6 for infection diagnosis. Best cutoff values of CRP for fever onset, 24 hours upon fever, 72 hours upon fever and long-standing fever were: 79, 120, 108 and 72 mg/l. At fever onset, sensitivity was 55.4 and specificity was 55.1. Best cutoff values of IL-6 for fever onset, 24 hours upon fever, 72 hours upon fever and long-standing fever were: 34, 32, 16 and 9 pg/ml. At fever onset, sensitivity and specificity were: 59.8 and 59.7. In the autologous' group, IL-6 presents significant values at initial moments. Independent risk factors identified in the multivariate analysis were: related donor, unrelated donor, Gram-negative infection, DHL ≥390 (UI/l), urea ≥25 (mg/dl) and CRP ≥120 (mg/l).
IL-6 and CRP are associated with the early diagnosis of clinically or microbiologically confirmed infection in post-HSCT febrile neutropenia. The association of the three biomarkers did not present any advantage, nor did it improve diagnostic accuracy. IL-6 was the only biomarker significantly associated at an early stage with infection when assessed only in patients submitted to autologous HSCT. The independent variables associated with death were: allogeneic transplantation, Gram-negative infection, DHL ≥390 UI/l at fever onset and urea ≥25 mg/dl at fever onset and CRP ≥120 mg/l.