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.
Highlights
In this cohort study of consecutive patients with cancer treated with standard first-line chemotherapy with complete follow-up, we found increased risk of all-cause and infectious mortality and intensive care unit (ICU) admissions in patients who experienced Febrile neutropenia (FN) during first-line treatment
Presenting with these risk factors most likely reflects a combination of the severity of the FN event and the prognosis associated with the underlying cancer
We found that positive blood cultures were associated with increased 30-day mortality but not later periods, an association found in noncancer patients.[24]
Summary
Febrile neutropenia (FN) is a critical complication of chemotherapy developing in 7.9%-11.7% of patients.[1,2] FN is associated with increased morbidity[3,4,5] and an in-hospital mortality rate around 10%4,6 and is a major dose-limiting event occurring during chemotherapy in patients with cancer.[1,4,7] Risk factors for short-term complications of FN (death, organ failure, or admission to the intensive care unit [ICU]) include age, cancer type, comorbidities, delayed antibiotics, and laboratory or vital sign abnormalities.[5,8,9,10] Different combinations of these risk factors have been used to develop the Talcott, MASCC, and CISNE risk scores[8,9,10] that have contributed widely to improve the management of FN. There are limited data on longer term outcomes after FN and their associated risk factors. Risk factors in relation to FN that are associated with increased morbidity and mortality are important to identify, both on short and long terms, to improve and strengthen the evidence base for clinical monitoring and prophylactic interventions
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