What is the recommended Filgrastim (Granulocyte-Colony Stimulating Factor, G-CSF) regimen for patients with Myelodysplastic Syndromes (MDS) experiencing neutropenia?

Filgrastim Regimen in MDS

For MDS patients with neutropenia, filgrastim should be administered at low doses (0.5-2 mcg/kg/day subcutaneously) on an intermittent basis for those with severe neutropenia (ANC <0.5 × 10⁹/L) and recurrent infections, rather than as continuous long-term therapy. 1

Clinical Context and Evidence Base

The use of filgrastim in MDS differs fundamentally from its use in chemotherapy-induced neutropenia. Prolonged or continuous treatment with G-CSF cannot be recommended in patients with MDS due to concerns about disease progression. 1 A randomized trial comparing G-CSF versus best supportive care demonstrated that while G-CSF increased neutrophil counts, overall survival was actually shorter in G-CSF recipients with refractory anemia and excess blasts, though the overall rate of transformation to AML was similar between groups. 1

Recommended Dosing Strategy

Initial Dosing

• Start with 0.5 mcg/kg/day subcutaneously for patients with severe neutropenia (ANC <0.5 × 10⁹/L) and recurrent infections 2
• If no response after 2 weeks, escalate to 1-2 mcg/kg/day 2
• Patients with congenital neutropenia may require higher doses (3-10 mcg/kg/day), but this is distinct from MDS 1

Response Criteria

• Target: ANC >1.5 × 10⁹/L with doubling of baseline ANC on at least 2 occasions 2
• Adjust doses to maintain neutrophil levels in the normal or low-normal range, not supranormal levels 1
• Response rates of approximately 80% can be expected across MDS subtypes (RA, RARS, RAEB) 2

Treatment Schedule and Duration

Intermittent administration is preferred over continuous therapy. 1 The evidence supports:

• Daily, alternate-day, or thrice-per-week subcutaneous administration (1-3 mcg/kg/day) for patients with idiopathic and cyclic neutropenia patterns 1
• Treatment duration in responders has been continued for 2-14 months (median 6 months) with persistent response in most cases 3
• Discontinue if no response is achieved or if disease progression occurs 1

Patient Selection Criteria

Appropriate Candidates

• MDS patients with severe neutropenia (ANC <0.5 × 10⁹/L) and recurrent infections 1
• Patients with RA or RARS subtypes (response rate ~81-90%) 2
• RAEB patients can also respond but require closer monitoring 2

High-Risk Features Requiring Caution

• Refractory anemia with excess blasts: These patients showed shorter overall survival with continuous G-CSF in randomized trials 1
• Age >65 years increases risk of complications 1
• Pre-existing cytogenetic abnormalities persist during G-CSF therapy, suggesting differentiation of the abnormal clone rather than elimination 4

Clinical Outcomes and Monitoring

Expected Benefits

• Neutrophil count increases in 80-90% of patients 4, 2
• Improved neutrophil function (chemotaxis and phagocytosis) 4
• Decreased infection rates in responders: only 1 responder experienced grade II infections compared to 5 non-responders (2 fatal) 3
• Some patients (16-46%) may experience improved erythropoiesis with decreased transfusion requirements 4

Monitoring Requirements

• Monitor ANC weekly during dose titration 2
• Assess for disease progression to AML at regular intervals 1
• Cytogenetic monitoring: abnormal clones typically persist, indicating induced differentiation rather than clonal suppression 4

Important Caveats and Pitfalls

What NOT to Do

• Do not use continuous, long-term prophylactic G-CSF in MDS patients, particularly those with excess blasts 1
• Do not use pegfilgrastim in MDS—there is no evidence supporting its use in this population, and its long-acting nature prevents dose adjustment 1
• Do not administer G-CSF concurrently with chemotherapy if treating MDS with intensive therapy 1

Adverse Effects

• Bone pain, arthralgias, and myalgias (usually diminish within first few weeks) 1
• Thrombocytopenia may occur or worsen 5
• Local erythema at subcutaneous injection sites 5
• Risk of accelerated progression to AML in severely affected patients requiring higher doses 1

Alternative Considerations

When G-CSF alone is insufficient:

• Combination with erythropoietin is being evaluated in ongoing trials for patients with both neutropenia and anemia 1
• GM-CSF (sargramostim) at very low doses (0.25-0.5 mcg/kg/day) has shown 64% response rates but is a category 2B recommendation 3, 1
• For patients progressing to AML, hematopoietic stem cell transplantation becomes the definitive alternative 1