Febrile Neutropenia and Long-term Risk of Infection Among Patients Treated With Chemotherapy for Malignant Diseases

Background: Febrile neutropenia (FN) is a common complication to chemotherapy, associated with increased short-term morbidity and mortality. However, the long-term outcomes after FN are poorly elucidated. We examined the long-term risk of infection and mortality rates in cancer patients with and without FN.

Methods: Patients aged >16 years treated with firstline chemotherapy were followed from 180 days after initiating chemotherapy until first infection, a new treatment with chemotherapy, death, or end of follow-up. Risk factors for infections were analyzed by competing risks regression, with death or another treatment with chemotherapy as competing events. Adjusted incidence rate ratios (aIRRs) of infection and death were analyzed using Poisson regression. In analyses of mortality, infection was included as a time-updated variable.

Results: We included 7190 patients with a median follow-up (interquartile range) of 0.58 (0.20-1.71) year. A total of 1370 patients had an infection during follow-up. The aIRRs of infection were 1.86 (95% confidence interval [CI], 1.56-2.22) and 2.19 (95% CI, 1.54-3.11) for patients with 1 or >1 episode of FN compared with those without FN. Mortality rate ratios were 7.52 (95% CI, 6.67-8.48) <1 month after, 4.24 (95% CI, 3.80-4.75) 1-3 months after, 2.33 (95% CI, 1.63-3.35) 3-6 months after, and 1.09 (95% CI, 0.93-1.29) >6 months after an infection, compared with the time before infection.

Conclusions: FN during chemotherapy is associated with a long-term increased risk of infection. Mortality rates are substantially increased for 6 months following an infection.