MOBILIZATION KINETICS OF PRIMITIVE HEMATOPOIETIC-CELLS FOLLOWING G-CSF WITH OR WITHOUT CHEMOTHERAPY FOR ADVANCED BREAST-CANCER

Background: The objective of this study was to determine the optimal c onditions for blood progenitor cell harvest for transplantation, with main emphasis on the mobilisation kinetics of primitive, marrow repopu lating cells. Patients and methods: Sixteen patients with advanced bre ast cancer were treated with 4 cycles of dose escalating FAC chemother apy (5-fluorouracil, adriamycin, cyclophosphamide) each followed by 10 mu g/kg/d G-CSF for 13 days. We assessed the number of colony-forming cells (CFC), and estimated the long-term culture initiating cells (LT C-IC) and CD34+ cells during the recovery phase of cycle 1 and 4 of ch emotherapy, and during additional periods of G-CSF administration eith er preceding or following the full course of chemotherapy. Results: Th e highest peak numbers of CFC per mi of blood (median 10489, range 860 -39282) were mobilised after the first cycle of chemotherapy. The lowe st peak numbers of CFC were obtained during the recovery phase from cy cle 4 (median 4739, range 40-26789). in contrast, the numbers of CD34 cells per mi of blood were significantly higher in cycle it (median 6 50, range 30-2600 x 10(2)) compared to those of cycle 1 (median 240, r ange 20-770 x 10(2)). The peak numbers of CFC mobilised by G-CSF befor e commencement and after the cessation of chemotherapy were equivalent , with a median of 5470 (range 1056-25669) and 5948 (range 2710-38975) per mi of blood, respectively. However, while mononuclear cells (MNC) collected at the days of maximal CFC mobilisation following G-CSF adm inistration before or after cycle 1 were similar to normal bone marrow MNCs in their ability to generate haemopoiesis when seeded onto perfo rmed irradiated stroma, those collected after cycle 4 or during G-CSF administration after the cessation of chemotherapy were markedly compr omised in this respect. Conclusions: Our results indicate that repeate d cycles of FAC chemotherapy followed by G-CSF result in a far lower n umber of LTC-IC than of CFC mobilised into the circulation. Furthermor e although the combination of chemotherapy and G-CSF mobilised the hig hest numbers of CFC, G-CSF alone pre-chemotherapy was more effective a t mobilising LTC-IC. These data indicate that neither the numbers of C FC mobilised nor the numbers of CD34+ cells are necessarily a reliable indicator for the putative marrow repopulating capability of the bloo d cells mobilised with chemotherapy plus G-CSF.