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Related Experiment Videos

Pegfilgrastim-induced hyperleukocytosis.

Ronald L Snyder1, Delevan J Stringham

  • 1Pharmacy Department, Children's Hospital of Orange County, Orange, CA 92868, USA. rsnyder@choc.org

The Annals of Pharmacotherapy
|August 2, 2007
PubMed
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Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacistsยท2007
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A high dose of pegfilgrastim (200 microg/kg) caused severe neutropenia overshoot in a pediatric patient, a rare side effect not previously reported in children. This case highlights the need for careful dosing of pegfilgrastim in pediatric oncology.

Area of Science:

  • Pediatric Oncology
  • Pharmacology
  • Hematology

Background:

  • Pegfilgrastim is a long-acting granulocyte colony-stimulating factor used to mitigate chemotherapy-induced neutropenia.
  • Its unique clearance mechanism involves saturable neutrophil receptor-mediated clearance, allowing for self-regulation of neutrophil counts.
  • Hyperleukocytosis is uncommon with pegfilgrastim, particularly in pediatric populations.

Observation:

  • A 3-year-old boy undergoing medulloblastoma therapy experienced severe neutropenia (WBC 0.1 x 10(3)/microL) after chemotherapy.
  • He received pegfilgrastim at a dose of 200 microg/kg.
  • Six days later, he presented with marked hyperleukocytosis (WBC 149 x 10(3)/microL) and neutrophilia (ANC 110 x 10(3)/microL), termed 'neutrophil overshoot'.

Findings:

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  • The elevated white blood cell count was attributed to pegfilgrastim, as other potential causes were excluded.
  • The Naranjo probability scale indicated pegfilgrastim as the probable cause of the adverse event.
  • The high pegfilgrastim dose of 200 microg/kg likely exceeded the receptor-mediated clearance capacity, impairing self-regulation.

    • Implications:

    • This case is the first reported instance of pegfilgrastim-induced hyperleukocytosis in a pediatric patient.
    • The findings suggest that the standard pediatric dose of pegfilgrastim may need further investigation to ensure safety and efficacy.
    • Further clinical trials are warranted to establish appropriate dosing of pegylated G-CSF in children to prevent adverse events like neutrophil overshoot.