Definition of Febrile Neutropenia
Febrile neutropenia is defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours, combined with an absolute neutrophil count (ANC) <0.5 × 10⁹/L or expected to fall below 0.5 × 10⁹/L. 1
Temperature Criteria
The fever component requires meeting one of two thresholds:
Some guidelines also recognize a single temperature ≥38.3°C as meeting criteria, though the ESMO definition using 38.5°C is most widely cited. 2
Neutrophil Count Criteria
The neutropenia component is defined as:
- ANC <0.5 × 10⁹/L (or <500 cells/μL) at presentation, OR 1
- ANC expected to fall below 0.5 × 10⁹/L within the next 48 hours based on chemotherapy timing and trajectory 1
This anticipated decline is critical—prophylaxis and treatment should be initiated even if the ANC has not yet reached <500 cells/μL if it is trending toward this threshold. 3
Clinical Context and Significance
Febrile neutropenia represents a medical emergency requiring immediate evaluation and empiric antibiotic therapy within 2 hours of presentation. 4
Key mortality and morbidity considerations include:
- Overall mortality is 5% in solid tumors (1% in low-risk patients) and up to 11% in hematological malignancies 1
- Mortality reaches 18% with Gram-negative bacteremia and 5% with Gram-positive bacteremia 1
- Patients with profound neutropenia (ANC <100 cells/μL) face the highest infection risk, with 10-20% developing bloodstream infections 4
- Duration of neutropenia >7 days significantly increases infection risk and mortality 4, 3
Common Pitfalls to Avoid
- Do not wait for ANC to fall below 500 cells/μL before acting—if chemotherapy timing suggests imminent decline to this level, treat as febrile neutropenia 3
- Fever remains the primary early indicator of infection in neutropenic patients, as other signs and symptoms are often absent or muted due to the lack of inflammatory response 4
- Even minor skin lesions can represent serious infections in this population and warrant thorough evaluation 5, 4
- Earlier antibiotic administration is associated with fewer complications—delays in treatment increase morbidity and mortality 4