What is the treatment approach for leukopenia to stimulate white blood cell production and prevent infections?

Treatment Approach for Leukopenia

Granulocyte colony-stimulating factor (G-CSF) is the primary treatment for severe leukopenia to stimulate white blood cell production and prevent infections, but should not be used routinely in patients with mild leukopenia or without neutropenia. 1

Risk Assessment and Indications for G-CSF Therapy

The approach to treating leukopenia depends on its severity, underlying cause, and associated risk factors:

Indications for G-CSF (Primary Prophylaxis):

• Chemotherapy regimens with ≥20% risk of febrile neutropenia 1
• Chemotherapy regimens with 10-20% risk of febrile neutropenia with additional risk factors 1
• Expected prolonged (≥10 days) and profound (≤0.1 x 10^9/L) neutropenia 1
• Age >65 years with uncontrolled primary disease 1
• Previous history of febrile neutropenia 1
• Extensive prior chemotherapy or radiation therapy 1

Contraindications for G-CSF:

• Patients without neutropenia suffering from community or hospital-acquired pneumonitis 1
• During chest radiotherapy (increased rate of complications and death) 1
• Immediately before or simultaneously with chemotherapy (risk of severe thrombocytopenia) 1
• Patients with moderate to severe SARS-CoV-2 infection (risk of exacerbating inflammatory pulmonary injury) 1

Treatment Protocol

For Chemotherapy-Induced Leukopenia:

1. Filgrastim (G-CSF):

   • Dosage: 5 μg/kg/day subcutaneously 1, 2
   • Timing: Start 24-72 hours after last day of chemotherapy 1
   • Duration: Continue until sufficient/stable ANC recovery 1
   • Note: Achieving a target ANC >10 x 10^9/L is not necessary 1

2. Pegfilgrastim (Long-acting G-CSF):

   • Dosage: Single dose of 6 mg subcutaneously 1, 2
   • Equally effective as daily filgrastim 1

For Severe Neutropenia with Fever (Febrile Neutropenia):

1. Immediate empirical broad-spectrum antibiotics 1
2. Consider adding G-CSF if high-risk features present 1:
   • Expected prolonged (≥10 days) neutropenia
   • Age >65 years
   • Uncontrolled primary disease
   • Pneumonia, hypotension, or sepsis syndrome
   • Invasive fungal infection
   • Hospitalized at time of fever development

For Leukopenia in Specific Conditions:

• Acute Myeloid Leukemia (AML): G-CSF can reduce time to neutrophil recovery and duration of fever following induction or consolidation chemotherapy 2
• Bone Marrow Transplantation: 10 μg/kg/day as intravenous infusion 2
• Congenital Neutropenia: Starting dose 6 μg/kg subcutaneously twice daily 2
• Cyclic or Idiopathic Neutropenia: Starting dose 5 μg/kg subcutaneously daily 2

Supportive Care Measures

1. Infection Prevention:

   • Personal hygiene and vigorous hand washing 1
   • Dental care 1
   • Reasonable environmental precautions against bacteria and fungi 1

2. Transfusion Support (if needed):

   • Platelet transfusions for counts <10 x 10^9/L 1
   • Consider higher threshold in presence of mucosal bleeding, infection, severe mucositis, or fever 1

3. Antifungal Prophylaxis (for prolonged neutropenia):

   • Consider drugs with antimold activity (itraconazole, posaconazole, or amphotericin) 1

Monitoring and Follow-up

• Regular complete blood count monitoring
• Assess for signs of infection
• Monitor for potential side effects of G-CSF:
  • Bone pain (common)
  • Splenic rupture (rare but serious) 2
  • Acute respiratory distress syndrome 2
  • Allergic reactions 2
  • Glomerulonephritis 2

Important Caveats

• G-CSF is not recommended for routine use in all neutropenic patients, as rates of febrile neutropenia and mortality are relatively low for most standard chemotherapies 1
• Avoid G-CSF in patients with myeloid neoplasms with overlap with myelodysplastic syndromes due to potential risk of disease progression 1
• Direct administration of less than 0.3 mL (180 mcg) of filgrastim is not recommended due to potential for dosing errors 2
• The development of filgrastim and pegfilgrastim has revolutionized oncology practice by enabling more aggressive chemotherapy regimens and treatment of a broader range of patients 3