Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Effecting use of filgrastim through ex-vivo analysis of hematopoietic progenitor cells: message in the medium

GM Higa PharmD, ML Auber MD

Mary Babb Randolph Cancer Center West Virginia University, Morgantown, WV USA,

AIM: To investigate the schedule-dependent effects of filgrastim on peripheral blood progenitor cells (PBPCs) in patients treated with myelosuppressive chemotherapy. METHODS: Patients with histologically confirmed malignancies who gave written informed consent were eligible if they developed an episode of neutropenia during the immediate prior treatment cycle and their treating oncologist decided to use supportive filgrastim with the next course of therapy. All patients received standard chemotherapy regimens given every 21-28 days. At study entry, patients were prospectively randomized to begin filgrastim, 5 microgram/kg/day subcutaneously either 24 hours after chemotherapy or when the ANC was <1000/microliter and continued until the postnadir ANC was at least 10,000/microliter. Patients were crossed over to the other filgrastim schedule with the next cycle. Complete blood counts were performed on a portion of blood samples collected twice weekly. The remaining volume of blood was used for ex-vivo analysis of PBPCs using semi-solid clonogenic assays and flow cytometry. Biological and clinical findings were simultaneously analyzed. RESULTS: 31 patients completed 89 cycles of treatment. Biologically, regardless of filgrastim schedule: 1) PBPCs were consistently assayed only after the neutrophil nadir and 2) quantitatively similar amounts of PBPCs were observed. Clinically, relative to the timing of filgrastim: 1) the total number of doses required to reach the ANC endpoint was significantly different and 2) only the day, not the rate, of neutrophil recovery is altered. Finally, a notable decrease in PBPCs was observed when filgrastim preceded chemotherapy by 72 hours although this did not impact neutrophil recovery. CONCLUSION: Quantitative analysis of hemopoietic progenitor cells suggest the following: 1) appearance of PBPCs is an indicator of increased granulopoietic activity and/or recovery which can be intensified by filgrastim, 2) filgrastim-enhanced marrow stimulation increases the cycling and sensitivity of progenitor cells to the lethal effects of cytotoxic agents, and 3) an ANC <1000/microliter has biological and clinical significance.

KEY WORDS: Filgrastim, PBPCs.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on chemotherapy.