Mobilisation kinetics of primitive haemopoietic cells following G-CSF with or without chemotherapy for advanced breast cancer

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Abstract
The objective of this study was to determine the optimal conditions for blood progenitor cell harvest for transplantation, with main emphasis on the mobilisation kinetics of primitive, marrow repopulating cells. Sixteen patients with advanced breast cancer were treated with 4 cycles of dose escalating FAC chemotherapy (5-fluorouracil, adriamycin, cyclophospharnide) each followed by 10 μg/kg/d G-CSF for 13 days. We assessed the number of colony-forming cells (CFC), and estimated the long-term culture initiating cells (LTC-IC) and CD34+ cells during the recovery phase of cycle 1 and 4 of chemotherapy, and during additional periods of G-CSF administration either preceding or following the full course of chemotherapy. The highest peak numbers of CFC per ml of blood (median 10489, range 860–39282) were mobilised after the first cycle of chemotherapy. The lowest peak numbers of CFC were obtained during the recovery phase from cycle 4 (median 4739, range 40–26789). In contrast, the numbers of CD34+ cells per ml of blood were sigrdicantly higher in cycle 4 (median 650, range 30–2600 × 102) compared to those of cycle 1 (median 240, range 20–770 × 102). The peak numbers of CFC mobilised by G-CSF before commencement and after the cessation of chemotherapy were equivalent, with a median of 5470 (range 1056–25669) and 5948 (range 2710–38975) per ml of blood, respectively. However, while mononuclear cells (MNC) collected at the days of maximal CFC mobilisation following G-CSF administration before or after cycle 1 were similar to normal bone marrow MNCs in their ability to generate haemopoiesis when seeded onto performed irradiated stroma, those collected after cycle 4 or during G-CSF administration after the cessation of chemotherapy were markedly compromised in this respect. Our results indicate that repeated cycles of FAC chemotherapy followed by G-CSF result in a far lower number of LTC-IC than of CFC mobilised into the circulation. Furthermore although the combination of chemotherapy and G-CSF mobilised the highest numbers of CFC, G-CSF alone pre-chemotherapy was more effective at mobilising LTC-IC. These data indicate that neither the numbers of CFC mobilised nor the numbers of CD34+ cells are necessarily a reliable indicator for the putative marrow repopulating capability of the blood cells mobilised with chemotherapy plus G-CSF.

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