Febrile Neutropenia

Febrile neutropenia is the most common oncologic emergency encountered in the hospital setting. Patients undergoing chemotherapy can experience severe and prolonged myelosuppression (leukopenia, anemia, and thrombocytopenia), which puts them at risk of life-threatening infections, particularly with gram-negative organisms (e.g., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Febrile neutropenia is a medical emergency because patients can deteriorate quickly (due to profound immunosuppression and risk of bacterial infections) without prompt medical treatment.

In this section, we review the definition of febrile neutropenia and provide algorithms outlining initial diagnostic workup and treatment, inpatient management, and empiric treatment for children with febrile neutropenia. However, please refer to institutional practices if they exist.

Febrile neutropenia is commonly defined as both:

1. oral or axillary temperature >100.4ᵒF (38ᵒC) on two separate occasions over 1 hour or a single temperature >101°F (38.3°C)*

and

2. absolute neutrophil count <500/mm³ (or anticipated to fall to <500/mm³ within 24-48 hours)

*Note: it is not necessary (nor recommended) to obtain a rectal temperature in a child receiving chemotherapy due to the risk of introducing fecal bacteria into the bloodstream through microtears, and the consequent risk of bacteremia in an immunocompromised host.

Treatment

Antibiotics: Current evidence suggests that earlier and prompt administration of antibiotics is associated with improved outcomes. Validated risk-stratification guidelines do not exist in pediatrics (unlike the Multinational Association for Supportive Care in Cancer [MASCC] risk-index score in adults). Therefore, the current standard of care is inpatient management of all febrile neutropenic pediatric patients.

Granulocyte colony-stimulating factor (G-CSF): G-CSF is often administered prophylactically after chemotherapy regimens in solid tumors and some lymphomas that are associated with moderate-to-high risk of febrile neutropenia to minimize the length of time that a patient is neutropenic and at risk for infection. However, G-CSF prophylaxis usually is not used in patients with leukemias to avoid stimulating the malignant clone, unless the patient also has documented bacteremia or life-threatening infection or G-CSF is part of a specific therapeutic approach (e.g., FLAG therapy in acute myeloid leukemia [AML]).