Jamali, Hussain (2004) 'In vitro' analysis of the 'in vivo' administration of filgrastim compared to pegfilgrastim on the mobilisation of human peripheral blood progenitor cells. (MSc(R) thesis), Kingston University, .

Abstract

Pegfilgrastim (Neulasta) is a modified version of the established. recombinant human granulocyte colony stimulating factor (G-CSF), intended for use in mobilisation of human stem/progenitor cells into the peripheral blood and for prophylaxis and treatment of chemotherapy induced neutropenia, though this thesis is concerned with the former use. Purpose: This present MSc thesis aims to compare the effect of daily in vivo administration of filgrastim (5[mu]g/kg/day) to dose-escalation of pegfilgrastim (6 mg/m-sup]2, 12 mg/m[sup]2 and 18 mg/m[sup]2) on the mobilisation ofhaemopoietic stem/progenitor cells. Patients and methods: A total of 20 patients suffering from various solid tumour malignancies (ovarian, fallopian tube, lung, and others) were enrolled for treatment with the combination of earboplatin (AUC 6) and paclitaxel (175 mg/m[sup]2) on day 1 of cycle 1. Patients were randomised to receive one of the following doses/agents on day 1 of cycle O and day 2 of cycle 1: (1) 6 mg/m[sup]2 ofpegfilgrastim, (2) 12 mg/m[sup]2 ofpegfilgrastim,(3) 18 mg/m[sup]2 of pegfilgrastim, and (4) 10 [mu]g/kg/day of daily filgrastim (see section 2). Analysis of CD34[sup]+ cells in vivo involved mononuclear cell (MNC) counting with a haemocytometer, fluorescent activated cell analysis, and short-term clonogenic assays Results: The results of this study showed that of the three doses of pegfilgrastim investigated, the 18 mg/m[sup]2 dose was the most effective in terms of CD34[sup]+ cell mobilisation, both pre and post chemotherapy. The other two doses, 6 mg/m[sup]2 and 12 mg/m[sup]2, resulted in comparable levels of CD34[sup]+ cells in both cycles, though at least 2- fold lower than the 18 mg/m[sup]2 dose. A comparison of the 18 mg/m[sup]2 dose and 10 [mu]g/kg/day of daily filgrastim, both in cycles O and 1, showed that there was no significant difference between them owing to the small patient numbers available. Conclusion: A single injection of pegfilgrastim (18 mg/m[sup]2 was shown to be at least equally effective as daily injections of filgrastim in the mobilisation of CD34[sup]+ cells. Such a result makes pegfilgrastim the preferred choice since it carries all the advantages of filgrastim, plus the advantage of once per cycle injection, making it more patient compliant.

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