What to do when absolute neutrophil count is low?

Management of Low Absolute Neutrophil Count

When the absolute neutrophil count (ANC) is low, management should be based on the severity of neutropenia, with prophylactic antimicrobial therapy for severe neutropenia (ANC <0.5 × 10^9/L) and consideration of granulocyte colony-stimulating factor (G-CSF) in specific clinical scenarios. 1

Classification of Neutropenia

• Neutropenia is defined as an ANC <1.5 × 10^9/L 2
• Severity classification:
  • Mild: ANC 1.0-1.5 × 10^9/L 2
  • Moderate: ANC 0.5-1.0 × 10^9/L 2
  • Severe: ANC <0.5 × 10^9/L 1

Initial Management Based on Severity

For Severe Neutropenia (ANC <0.5 × 10^9/L):

• Implement broad-spectrum prophylactic antimicrobial therapy: 1
  • Fluoroquinolone with streptococcal coverage OR
  • Fluoroquinolone without streptococcal coverage plus penicillin
  • Add antiviral therapy (acyclovir or congeners)
  • Add antifungal therapy (fluconazole)
• Continue antimicrobial prophylaxis until: 1
  • ANC recovers to ≥0.5 × 10^9/L OR
  • Patient develops neutropenic fever requiring change in antimicrobial strategy

For Moderate Neutropenia (ANC 0.5-1.0 × 10^9/L):

• Monitor closely for signs of infection 2
• No routine antimicrobial prophylaxis unless additional risk factors present 2, 3

For Mild Neutropenia (ANC 1.0-1.5 × 10^9/L):

• Generally no specific intervention needed 2
• Identify and address underlying cause 3

Management of Febrile Neutropenia

• For patients who develop fever (>38.5°C for >1 hour) with ANC <0.5 × 10^9/L: 1
  • Discontinue prophylactic fluoroquinolone if being used 1
  • Initiate empiric therapy directed at gram-negative bacteria (particularly Pseudomonas aeruginosa) 1
  • Follow Infectious Diseases Society of America guidelines for management 1

Use of Granulocyte Colony-Stimulating Factor (G-CSF)

Indications for G-CSF:

1. Chemotherapy-induced neutropenia: 1, 4

   • Primary prophylaxis when risk of febrile neutropenia >20%
   • Reactive treatment when low/intermediate-risk regimens result in grade 3/4 neutropenia

2. After bone marrow transplantation: 1, 4

   • 10 mcg/kg/day intravenously
   • Start at least 24 hours after chemotherapy and bone marrow infusion

3. Severe chronic neutropenia: 4, 2

   • Congenital neutropenia: 6 mcg/kg twice daily subcutaneously
   • Idiopathic/cyclic neutropenia: 5 mcg/kg once daily subcutaneously

G-CSF Administration Guidelines:

• Standard dose: 5 mcg/kg/day subcutaneously 1, 4
• Continue until ANC recovery (sufficient/stable) 1
• Do not aim for ANC >10 × 10^9/L 1, 4
• Contraindicated during chest radiotherapy 1
• Do not administer within 24 hours before chemotherapy 4

Monitoring

• For patients on antimicrobial prophylaxis:

  • Monitor for breakthrough infections 1
  • Adjust therapy if neutropenic fever develops 1

• For patients receiving G-CSF:

  • Monitor CBC twice weekly during therapy 4
  • Discontinue G-CSF if ANC exceeds 10 × 10^9/L 4

• For patients with chronic neutropenia on G-CSF:

  • Monitor CBC with differential and platelet counts weekly for first 4 weeks 4
  • Then monthly during first year if clinically stable 4

Special Considerations

• For neutropenia in transplant recipients:

  • Consider reducing immunosuppressive medications when appropriate 5
  • Address nutritional deficiencies if present 5
  • Treat underlying viral infections if identified 5

• For chemotherapy patients:

  • If neutropenia persists despite G-CSF, consider chemotherapy dose reduction 6
  • Resume therapy at full dose if ANC recovers to >1.0 × 10^9/L 6

Pitfalls and Caveats

• Do not use G-CSF in patients without neutropenia, particularly those with community or hospital-acquired pneumonia 1
• Risk of severe thrombocytopenia when G-CSF is given immediately before or with chemotherapy 1
• Long-term G-CSF use may be associated with small increased risk of myelodysplastic syndrome or acute myeloid leukemia 1
• Avoid gut decontamination with antibiotics unless specifically indicated (e.g., abdominal wound) as altering gut flora may worsen outcomes 1