Should filgrastim (Granulocyte-Colony Stimulating Factor) be given to a patient with Myelodysplastic Syndrome (MDS) and low Absolute Neutrophil Count (ANC)?

Filgrastim Use in MDS Patients with Low ANC

Filgrastim should be given to MDS patients with severe neutropenia (ANC <0.5 × 10⁹/L) and recurrent infections, but only at low doses (0.5-2 mcg/kg/day) on an intermittent schedule—never as continuous long-term therapy, as prolonged use may shorten overall survival, particularly in patients with excess blasts. 1

Dosing Strategy

Start with 0.5-1 mcg/kg/day subcutaneously rather than the standard 5 mcg/kg/day used in chemotherapy-induced neutropenia. 1 This low-dose approach is critical in MDS because:

• Lower doses (0.5-2 mcg/kg/day) are effective in raising neutrophil counts in approximately 64-73% of MDS patients with neutropenia 2, 3
• Higher doses increase risk of blast proliferation and disease progression without additional benefit 1, 4
• Dose escalation to 1-2 mcg/kg/day can be attempted if no response occurs after 2-4 weeks 2, 4

Administration Schedule

Use intermittent dosing (daily, alternate-day, or 2-3 times per week) rather than continuous therapy. 1 The intermittent approach:

• Maintains protective neutrophil levels while minimizing exposure 5
• Reduces risk of disease progression compared to continuous administration 1
• Can be continued for 2-14 months (median 6 months) in responders 2

Patient Selection Criteria

Appropriate candidates include:

• Severe neutropenia (ANC <0.5 × 10⁹/L) with recurrent infections 1, 6
• Refractory anemia (RA) or RA with ringed sideroblasts (RARS) have the highest response rates (approximately 90%) compared to RAEB (47%) 2
• Baseline ANC >0.5 × 10⁹/L predicts better response (80% vs 55% for ANC <0.5) 2

Critical Contraindications and Warnings

Do NOT use filgrastim in the following MDS scenarios:

• Refractory anemia with excess blasts (RAEB) requires extreme caution, as randomized trials showed shorter overall survival with continuous G-CSF 1, 7
• Concurrent with chemotherapy if treating MDS with intensive therapy 1
• Pegfilgrastim should never be used in MDS—no evidence supports its use, and its long-acting nature prevents dose adjustment 1, 6
• Continuous long-term prophylactic therapy is contraindicated due to progression risk 1

Monitoring and Response Assessment

Target ANC of 1.0-5.0 × 10⁹/L rather than normal levels. 5 Monitor for:

• Blast count increases—occurred in 5/29 patients in one series, all with RAEB or RAEBT 4
• Thrombocytopenia—can occur even without blast progression 4, 7
• Cytogenetic abnormalities—MDS and AML transformation risk is inherent to congenital neutropenia and may be increased with prolonged G-CSF 7
• Response typically occurs within 2-4 weeks of initiation 2, 3

Expected Clinical Benefits

Filgrastim in MDS provides:

• Reduced infection risk when ANC maintained >1.5 × 10⁹/L 3
• Neutrophil count increases of 3.6- to 16.3-fold in responders 3
• Improved bone marrow myeloid maturation in 78% of patients 3
• Possible reduction in transfusion requirements in some patients 3

Treatment Algorithm

1. Confirm severe neutropenia (ANC <0.5 × 10⁹/L) with recurrent infections 1
2. Verify FAB subtype—RA/RARS preferred; use extreme caution in RAEB 2, 1
3. Start filgrastim 0.5-1 mcg/kg/day subcutaneously on intermittent schedule 1, 2
4. Assess response at 2-4 weeks—target ANC 1.0-5.0 × 10⁹/L 5, 2
5. If no response, escalate to 1-2 mcg/kg/day 2, 4
6. If response achieved, continue for 2-14 months with ongoing monitoring 2
7. Discontinue immediately if: blast count rises, disease progression occurs, or no response after dose escalation 1, 2

Common Pitfalls to Avoid

• Using standard chemotherapy doses (5 mcg/kg/day)—this is too high for MDS and increases toxicity risk 1
• Continuing therapy without response—discontinue if no improvement after appropriate dose escalation 1
• Treating patients without severe neutropenia or infections—prophylactic use is not indicated 1
• Failing to monitor blast counts—can increase in 17% of RAEB patients 4
• Using in patients with high blast counts without careful risk-benefit assessment 1, 7