title: Pegfilgrastim successfully mobilizes megakaryocyte progenitors into the peripheral blood in subjects with solid tumours.
abstract: Cytokine-mobilized PBPC transplants result in rapid neutrophil and platelet engraftment following high-dose chemotherapy. A total of 61 patients with solid tumours, sensitive to carboplatin and paclitaxol, were recruited as part of a phase I/II study and randomized to receive a single dose of 6, 12 or 18 mg pegfilgrastim on day 1 of a 14-day prechemotherapy cycle or daily filgrastim (10 microg/kg) for up to 7 days. The kinetics of megakaryocyte progenitor mobilization were studied using immunohistochemical assays and flow cytometry in a subset of 31 patients. There was no significant difference among treatment groups with respect to the timing of total progenitor colony-forming units (CFUs) and megakaryocyte progenitor (CFU-MK) mobilization, with the highest median peak falling on day 4/5 in all groups. In the pegfilgrastim 18 mg group, the mean peak total CFUs and CFU-MK were statistically significantly higher than in the filgrastim group (2.031x10(4) vs 8.06x10(3) per millilitre, P=0.024 and 1.12x10(4) vs 4.56x10(3) per millilitre, P=0.024, respectively). The kinetic profiles generated using immunohistochemical assays for CFU-MK and FACS analysis for CD41a were closely correlated suggesting that CD41a can be used as a surrogate marker for megakaryocytic mobilization.
authors.affiliation: Department of Haematology, St George's Hospital Medical School, University of London, London, UK. fwillis@sgul.ac.uk
authors.forename: F
authors.initials: F
authors.lastname: Willis
authors.forename: D
authors.initials: D
authors.lastname: Theti
authors.forename: S
authors.initials: S
authors.lastname: Dean
authors.forename: P
authors.initials: P
authors.lastname: Bacon
authors.forename: N
authors.initials: N
authors.lastname: Baker
authors.forename: R
authors.initials: R
authors.lastname: Pettengell
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D000069585:Filgrastim; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D017239:Paclitaxel / Q000627:therapeutic use; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013234:Stem Cells / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim