Biological effects of pegfilgrastim on circulating neutrophils in breast cancer patients undergoing dose-dense chemotherapy.
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.
Department of Internal Medicine, University of Pavia and Fondazione IRCCS Policlinico S Matteo, Pavia, Italy. r.invernizzi@smatteo.pv.it
Rosangela
R
Invernizzi
Donatella
D
Grasso
Erica
E
Travaglino
Chiara
C
Benatti
Elena
E
Collovà
Mariangela
M
Manzoni
Luca
L
Livraghi
Marco
M
Danova
Alberto
A
Riccardi
D000199:Actins / Q000378:metabolism; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007958:Leukocyte Count; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000199:Actins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000469:Alkaline Phosphatase; D000069585:Filgrastim