How to manage a patient with severe neutropenia?

Management of Severe Neutropenia

Patients with severe neutropenia (ANC <500 cells/mm³) should receive prompt intervention including antimicrobial therapy for febrile episodes, consideration of colony-stimulating factors, and management of the underlying cause to reduce morbidity and mortality. 1

Initial Assessment and Risk Stratification

• Determine if the neutropenia is high-risk or low-risk based on severity, duration, and clinical stability 1
• High-risk patients include those with:
  • Profound neutropenia (ANC <100 cells/mm³) expected to last >7 days 1
  • Significant medical comorbidities (uncontrolled cancer, COPD, poor functional status) 1
  • Clinical instability (hypotension, altered mental status, uncontrolled pain) 1
  • Underlying conditions like acute leukemia or those undergoing HSCT 1
• Low-risk patients include those with:
  • Brief expected neutropenia (<7 days) 1
  • Few or no comorbidities 1
  • Clinical stability 1

Management of Febrile Neutropenia

Initial Antimicrobial Therapy

• For febrile neutropenia (temperature ≥38.3°C or ≥38.0°C for ≥1 hour), initiate broad-spectrum antibiotics immediately 1
• High-risk patients should be hospitalized for IV antibiotics 1
• Low-risk patients may be candidates for oral antibiotics 1

Assessment at 48 Hours

• If afebrile and ANC ≥0.5 × 10⁹/L:
  • Low-risk: Consider changing to oral antibiotics 1
  • High-risk: If on dual therapy, aminoglycoside may be discontinued 1
• If still febrile at 48 hours:
  • Clinically stable: Continue initial antibacterial therapy 1
  • Clinically unstable: Broaden antibiotic coverage and seek expert infectious disease consultation 1

Duration of Antimicrobial Therapy

• If ANC ≥0.5 × 10⁹/L, patient is asymptomatic, afebrile for 48 hours, and blood cultures negative: discontinue antibiotics 1
• If ANC <0.5 × 10⁹/L but patient has been afebrile for 5-7 days without complications: discontinue antibiotics 1
• Exception: High-risk cases with acute leukemia or post-high-dose chemotherapy may continue antibiotics for up to 10 days or until ANC ≥0.5 × 10⁹/L 1

Antifungal Considerations

• If fever persists >4-6 days, consider initiating antifungal therapy 1
• Perform chest CT scan to evaluate for fungal infection 1
• Options for presumed aspergillosis include voriconazole or liposomal amphotericin B 1
• For suspected candidiasis, consider liposomal amphotericin B or an echinocandin if patient has had prior azole exposure 1

Use of Colony-Stimulating Factors (CSFs)

• Filgrastim (G-CSF) is indicated to decrease the incidence of infection in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy 2
• Recommended starting dose is 5 mcg/kg/day administered as a single daily subcutaneous injection 2
• Continue daily administration until ANC has reached 10,000/mm³ following the expected chemotherapy-induced nadir 2
• For severe chronic neutropenia (congenital, cyclic, or idiopathic), G-CSF is indicated to reduce the incidence and duration of neutropenia-related sequelae 2

Infection Prevention Measures

• Maintain good skin integrity with daily inspection of potential infection portals 1
• Practice good oral and dental hygiene 1
• Avoid rectal thermometers, enemas, suppositories, and rectal examinations 1
• Avoid plants, dried or fresh flowers in the rooms of hospitalized neutropenic patients 1
• Healthcare workers with transmissible infections should not provide direct patient care 1

Dietary Considerations

• Well-cooked foods are typically recommended 1
• Avoid prepared luncheon meats 1
• Well-cleaned, uncooked raw fruits and vegetables are acceptable 1

Special Considerations

• For patients with neutropenia but no fever, routine use of CSFs is not recommended 1
• For patients with persistent fever despite neutrophil recovery, consider infectious disease consultation and antifungal therapy 1
• For high-risk neutropenic patients (ANC <100 cells/mm³, ≥7 days following cytotoxic chemotherapy), prophylactic antimicrobial therapy and prompt initiation of treatment for febrile illness is standard of care 1

Monitoring

• Perform daily assessment of fever trends, bone marrow and renal function until the patient is afebrile and ANC ≥0.5 × 10⁹/L 1
• Monitor complete blood counts and platelet counts frequently 2
• For patients on ruxolitinib with neutropenia, monitor CBCs every 2-4 weeks until doses are stabilized 1