Mortality and admission to intensive care units after febrile neutropenia in patients with cancer

Abstract

Febrile neutropenia (FN) is a critical complication of chemotherapy associated with increased in-hospital mortality. However, associations with increased mortality and intensive care unit (ICU) admissions during longer follow-up are not established. Patients treated with standard first-line chemotherapy for solid cancers at Rigshospitalet, Denmark in 2010-2016 were included. Incidence rate ratios (IRR) of all-cause, infectious and cardiovascular mortality, and ICU admissions after FN were analyzed by Poisson regression. Risk factors at the time of FN were analyzed in the subpopulation of patients with FN; all-cause mortality was further stratified by the time periods 0-30, 31-365, and 366+ days after FN. We included 9018 patients with gastric (14.4%) and breast (13.1%) cancer being the most common, 51.2% had locally advanced or disseminated disease and the patients had a median Charlson Comorbidity Index score of 0 (interquartile range, 0-0). During follow-up, 845 (9.4%) experienced FN and 4483 (49.7%) died during 18 775 person-years of follow-up. After adjustment, FN was associated with increased risk of all-cause mortality, infectious mortality, and ICU admissions with IRRs of 1.39 (95% CI, 1.24-1.56), 1.94 (95% CI, 1.43-2.62), and 2.28 (95% CI, 1.60-3.24). Among those with FN, having a positive blood culture and low lymphocytes were associated with excess risk of death and ICU admissions (predominantly the first 30 days after FN), while elevated C-reactive protein and low hemoglobin predicted mortality the first year after FN. The risk of death varied according to the time since FN; adjusted IRR per additional risk factor present for the time periods 0-30, 31-365, and 366+ days after FN were 2.00 (95% CI, 1.45-2.75), 1.36 (95% CI, 1.17-1.57), and 1.17 (95% CI, 0.98-1.41). FN was associated with increased mortality and risk of ICU admissions. An objectively identifiable subgroup of patients among those with FN carried this excess risk.

Keywords: cancer; febrile neutropenia; infection; mortality; prognosis.

FIGURE 1

Flow diagram for inclusion of patients with cancer initiating standard first‐line chemotherapy in 2010‐2016

FIGURE 2

Kaplan‐Meier plot of all‐cause mortality after febrile neutropenia according to the number of risk factors present at the time of febrile neutropenia. Number of risk factors was calculated based on how many of the following the patient had present at the time of febrile neutropenia: positive blood culture, CRP ≥79 mg/L, hemoglobin ≤10.6 g/dL, and lymphocytes ≤600/µL. CRP, C‐reactive protein