Biological effects of pegfilgrastim on circulating neutrophils in breast cancer patients undergoing dose-dense chemotherapy

Rosangela Invernizzi, Donatella Grasso, Erica Travaglino, Chiara Benatti, Elena Collovà, Mariangela Manzoni, Luca Livraghi, Marco Danova, Alberto Riccardi

Research output: Contribution to journalArticle

Abstract

Pegfilgrastim is a covalent conjugate of filgrastim and polyethylene glycol that has proved to be effective in supporting myelopoiesis during chemotherapy. Since very limited information is available on the biological effects of pegfilgrastim on neutrophils exposed to chemotherapy, we analyzed the following parameters in neutrophils of patients undergoing dose-dense chemotherapy for breast cancer: apoptosis, by a TUNEL technique; actin polymerization, using FITC-labeled phalloidin, and alkaline phosphatase activity by cytochemistry. Peripheral blood buffy coat smears were obtained before starting treatment and immediately before each chemotherapy course. After pegfilgrastim stimulation we observed the following: (1) stability of the absolute neutrophil count for the whole duration of treatment and no infectious events; (2) a reduction in the neutrophil constitutive apoptosis rate in comparison with that observed in control patients treated with standard chemotherapy courses with no growth factor support; (3) persistent abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeletal organization, and (4) a significant increase in the activity of leukocyte alkaline phosphatase, a sensitive marker of the later stages of neutrophil maturation. In conclusion, these results suggest that pegfilgrastim improves the neutrophil functions in patients exposed to chemotherapy by inhibition of constitutive apoptosis, thereby prolonging the survival of these cells.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalOncology
Volume75
Issue number3-4
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Actin cytoskeleton
  • Breast cancer
  • Dose-dense chemotherapy
  • Neutrophil apoptosis
  • Pegfilgrastim

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Invernizzi, R., Grasso, D., Travaglino, E., Benatti, C., Collovà, E., Manzoni, M., Livraghi, L., Danova, M., & Riccardi, A. (2008). Biological effects of pegfilgrastim on circulating neutrophils in breast cancer patients undergoing dose-dense chemotherapy. Oncology, 75(3-4), 237-244. https://doi.org/10.1159/000164588