Can leucocytosis be expected after pegfilgrastim (pegylated filgrastim) administration?

Leukocytosis Following Pegfilgrastim Administration

Yes, leukocytosis can be expected after pegfilgrastim administration, as it is a known potential effect documented in clinical guidelines and the FDA drug label. 1

Mechanism and Expected Effects

• Pegfilgrastim (pegylated filgrastim) is a long-acting form of granulocyte colony-stimulating factor (G-CSF) developed to reduce the inconvenience of daily G-CSF injections 2
• The primary purpose of pegfilgrastim is to stimulate neutrophil production after myelosuppressive chemotherapy, which inherently leads to increased white blood cell counts 2
• According to the FDA drug label, leukocytosis (WBC counts > 100 x 10^9/L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving pegfilgrastim in clinical studies 1

Clinical Evidence of Leukocytosis

• The Update Committee for the American Society of Clinical Oncology guidelines specifically expressed concern about potential leukocytosis following pegfilgrastim administration 2
• Case reports have documented significant leukocytosis after pegfilgrastim administration:
  • A pediatric case reported WBC counts reaching 149 x 10^3/μL with ANC of 110 x 10^3/μL after pegfilgrastim administration 3
  • A young breast cancer patient experienced progressive leukocytosis with increasing ANC values (from 2,700 to 15,000/mm^3) on day 1 of each chemotherapy cycle following pegfilgrastim administration 4

Timing of Leukocytosis

• The timing of pegfilgrastim administration can affect the occurrence and severity of leukocytosis:
  • Administration at 24 hours after chemotherapy resulted in higher rates of early leukocytosis (75% in anthracycline cycles) compared to administration at 72 or 96 hours 5
  • Patients receiving pegfilgrastim 24 hours after chemotherapy experienced the highest median WBC counts (61.2-67.8 x 10^3/μL) 5
  • Administration at 96 hours after chemotherapy was associated with higher rates of late leukocytosis (day 13) 5

Risk Factors and Management

• Overdosage of pegfilgrastim may result in more severe leukocytosis and bone pain 1
• Higher doses appear to increase risk of leukocytosis, as seen in a pediatric case where 200 μg/kg (exceeding the typical 100-110 μg/kg dose) led to significant hyperleukocytosis 3
• In cases of severe leukocytosis:
  • Dose reduction may be effective in managing symptoms while maintaining efficacy 4
  • Monitoring WBC counts is important, especially in patients who appear to be high responders to pegfilgrastim 4

Clinical Implications

• Despite concerns about leukocytosis, pegfilgrastim has been shown to be effective in reducing the risk of febrile neutropenia compared to filgrastim (11% vs 19%) 2
• The standard adult dose of pegfilgrastim is 6 mg administered once 1-3 days after chemotherapy 2
• For most patients, the benefits of preventing febrile neutropenia outweigh the risks of transient leukocytosis 6

Monitoring Recommendations

• Monitor WBC counts after pegfilgrastim administration, particularly in patients who appear to be high responders 4
• Be vigilant for signs of complications from extreme leukocytosis, though no complications attributable to leukocytosis were reported in clinical studies 1
• Consider dose reduction in patients who experience significant leukocytosis or severe symptoms 4

Leukocytosis following pegfilgrastim administration is an expected pharmacological effect that typically resolves without intervention. However, monitoring is recommended, particularly in patients receiving higher doses or those who have previously demonstrated high sensitivity to the medication.