Classification of Febrile Neutropenia
Febrile neutropenia is classified based on two key parameters: absolute neutrophil count (ANC) severity and patient risk stratification, with the fundamental definition being ANC <0.5 × 10⁹/L (or <500 cells/µL) combined with fever >38.5°C for >1 hour. 1, 2
Neutropenia Severity Classification
The severity of neutropenia itself is stratified into three categories that determine infection risk and management intensity:
- Mild neutropenia: ANC 1.0-1.5 × 10⁹/L - requires monitoring but minimal intervention 2, 3
- Moderate neutropenia: ANC 0.5-1.0 × 10⁹/L - requires closer monitoring 3
- Severe neutropenia: ANC <0.5 × 10⁹/L - requires immediate intervention and consideration of prophylactic antimicrobial therapy 2, 3, 4
When fever (>38.5°C for >1 hour) occurs with ANC <0.5 × 10⁹/L, this constitutes febrile neutropenia and represents a medical emergency requiring immediate evaluation. 2, 3
Risk Stratification of Febrile Neutropenia
Beyond the ANC threshold, febrile neutropenia patients are further classified by risk level:
- High-risk patients: Those with ANC <100 cells/µL (profound neutropenia) anticipated to last >7 days 3, 5
- Low-risk patients: Can be identified using the Multinational Association for Supportive Care (MASCC) score, where scores ≥21 indicate low risk and scores <21 indicate high risk 3
Critical Classification Factors
Depth of Neutropenia
- Risk of infection increases significantly when ANC falls below 500 cells/µL 3
- Highest risk occurs when neutrophils are <100/µL (profound neutropenia) 3
- Important caveat: Patients presenting with ANC >500 cells/µL after recent chemotherapy who are expected to have continued decline are actually at high risk for bloodstream infection, invasive fungal disease, and ICU admission - clinicians should not be falsely reassured by the initial higher count 5
Duration of Neutropenia
- Patients with anticipated prolonged neutropenia (>7 days) are at higher risk for infectious complications 3
- Duration of neutropenia >7 days prior to the febrile episode is an independent risk factor for bloodstream infection 5
Common Pitfalls to Avoid
- Do not delay evaluation of fever in neutropenic patients - even mild fever in severe neutropenia requires immediate attention 3
- Do not overlook minor skin lesions in neutropenic patients as these can represent serious infections 3
- Do not be reassured by initial ANC >500 cells/µL if the patient recently received chemotherapy and continued decline is expected, as this group has higher rates of invasive fungal disease and bloodstream infection 5