Grades of Neutropenia in Chemotherapy
Neutropenia in chemotherapy is graded based on the absolute neutrophil count (ANC), with Grade 4 neutropenia being the most severe and associated with highest risk of complications.
Neutropenia Grading System
- Grade 1 Neutropenia: ANC 1500-2000/mm³ (mild neutropenia) 1
- Grade 2 Neutropenia: ANC 1000-1500/mm³ (moderate neutropenia) 1
- Grade 3 Neutropenia: ANC 500-1000/mm³ (severe neutropenia) 1
- Grade 4 Neutropenia: ANC <500/mm³ (life-threatening neutropenia) 1, 2
Clinical Significance of Neutropenia Grades
Febrile Neutropenia
- Febrile neutropenia is defined as an axillary temperature >38.5°C for >1 hour with an ANC <500/mm³ 1
- Represents a medical emergency requiring prompt intervention 1
- Mortality rates in febrile neutropenia range from 0-7% in standard chemotherapy regimens 1
Risk Assessment
- High-risk regimens: Those with expected neutropenia rate >50%, such as 3-drug combinations including lenalidomide plus alkylating agents 3
- Low-risk regimens: Combinations of novel agents with dexamethasone alone 3
- Grade 4 neutropenia incidence >65% predicts higher risk for febrile neutropenia and other adverse outcomes 2
Management Based on Neutropenia Grade
Grade 3 Neutropenia (ANC 500-1000/mm³)
- Monitor closely for fever and signs of infection 1
- Consider dose modifications for subsequent chemotherapy cycles 1
- For persistent Grade 3 neutropenia (>2 weeks), consider dose reduction or growth factor support 1
Grade 4 Neutropenia (ANC <500/mm³)
- Hold chemotherapy until ANC recovery to ≥1000-1500/mm³ 1
- Resume at reduced dose if neutropenia persists beyond expected recovery time 1
- Consider granulocyte colony-stimulating factors (G-CSF) for management 3
- Hospitalization and broad-spectrum antibiotics if febrile 1
G-CSF Prophylaxis Recommendations
Primary Prophylaxis (Before Neutropenia Occurs)
- Recommended for high-risk chemotherapy regimens (>20% risk of febrile neutropenia) 3, 4
- Consider for intermediate-risk regimens (10-20% risk) with additional risk factors 3
- Standard dose: 5 μg/kg/day of G-CSF subcutaneously 24-72 hours after chemotherapy until ANC recovery 1
- Pegfilgrastim (6 mg single dose) is equally effective as daily G-CSF 1, 5
Secondary Prophylaxis (After Neutropenia Episode)
- Indicated when patients experience Grade 3/4 neutropenia with prior cycles 3
- If ANC recovers to >1000/mm³, therapy can resume without dose modifications 3
- If severe neutropenia persists, delay treatment until ANC >1000/mm³ and implement dose reductions 3
Special Considerations
- G-CSF is contraindicated during chest radiotherapy due to increased complications and mortality 1
- Pretreatment absolute monocyte count <370/mm³ and/or absolute neutrophil count <3500/mm³ may predict higher risk for febrile neutropenia 6
- Neutropenia incidence varies by malignancy type: approximately 10% in breast cancer patients versus 40% in lymphoma patients receiving moderate/high-risk chemotherapy 4