Abstract
10521 Background: The dose and schedule of chemotherapy (CT), that play a crucial role in the outcome of pts with chemosensitive tumors, were made feasible with the primary use of colony stimulating factors. Few data are available on the in vivo biological effects of the “long-lasting” cytokine pegfilgrastim. We have focused on the cytokinetic effects on the CD34+/38+ peripheral blood (PB) progenitor cell subset and on its influence on neutrophils functional parameters. Methods: We studied PB samples from 14 breast cancer pts (median age 47 yrs; 35–61 yrs), treated with Docetaxel (80 mg/sqm, d 1) + Epirubicin (75 mg/sqm, d 1) + pegfilgrastim (6 mg s.c. on d +1). The % of CD34+/38+ circulating progenitor cells (CPCs) (sorted with immunomagnetic procedure) undergoing G0/G1, S and G2/M phases of the cell cycle or showing apoptotic features were evaluated using flow cytometry. Annexin V was quantitated at a single cell level and correlated with cell cycle phases. On PB buffy coat smears, alkaline phosphatase activity by cytochemistry, actin polymerization using FITC-labelled phalloidin and apoptosis by TUNEL technique, were evaluated on neutrophils. Results: Seven days following CT + pegfilgrastim the CD34+/38+ absolute numbers were: 46 (27–74) and 41 (25–66) on day 14+ from CT.On day 7+ the % of CD34+/38+ CPCs in S-phase was 13.0 ± 9 while 3.7% ± 6 of this cell subset showed apoptotic features. One week later, these values were 8.4% ± 7 and 7.7% ± 5, respectively. We also observed: stability of the absolute neutrophil count for all the duration of treatment; a significant increase of the leucocyte alkaline phosphatase; abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeleton organization, and a significant reduction of neutrophil apoptosis. Conclusions: 1) pegfilgrastim exerts stimulatory effects on cell cycle status of PB CD34+/38+ CPCs, protecting them from apoptosis; this is evident 7 days after its administration and tends to decrease one week later 2) pegfilgrastim improves the neutrophil function by inhibiting their accelerated apoptosis and prolonging survival. These data could be useful when dose-dense CT is planned with pegfilgrastim support. No significant financial relationships to disclose.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
