Early Discontinuation versus Continuation of Antimicrobial Therapy in Low Risk Pediatric Cancer Patients with Febrile Neutropenia, Before Recovery of Counts: A Randomized Controlled Trial (DALFEN Study).

Objective: To determine if early discontinuation of antimicrobials in pediatric patients with low risk febrile neutropenia is as effective as continuing therapy before recovery of counts, in an outpatient setting.
Methods: In an open label, non-inferiority, randomized controlled phase 3 trial at a tertiary cancer center, patients aged 3-18 y, with low risk febrile neutropenia were started on empirical intra-venous antibiotics in an outpatient setting. Randomization was done when the patients became afebrile for at least 24 h; standard arm consisted of oral antibiotics, while antibiotics were stopped in the experimental arm. Enrolled patients were followed for re-appearance of fever and rate of re-admission, until ANC ≥ 500. A pilot feasibility randomized study with similar design preceded this trial.
Results: From Jan 2017-Dec 2018, 75 patients were randomized: 38 to stoppage arm while 37 patients received oral antibiotics. Baseline characteristics were equally matched. Success rates were 94.6% in the continuation arm vs. 94.7% in the stoppage arm; absolute risk difference was 0.1% (95% CI: -10.0% to +10.3%), thus suggesting that the experimental arm is non-inferior to the standard arm. There was no re-admission on failure in any arm.
Conclusions: Antimicrobial therapy in low risk afebrile neutropenic patients can be stopped early. This approach can lead to significant cost and resource benefits.