Stem cell mobilization with G-CSF alone in breast cancer patients:: higher progenitor cell yield by delivering divided doses (2x5 μg/kg) compared to a single dose (1x10 μg/kg)

We investigated the schedule dependency of G-CSF (10 mu g/kg) alone in mobilizing peripheral blood progenitor cells (PBPC) in breast cancer patients, After a median of three cycles (range, 2-6) of anthracycline-based chemotherapy, 49 patients with breast cancer (stage II/III, greater than or equal to 10+ Ln n = 36; locally advanced/inflammatory n = 8, stage IV (NED) n = 5) underwent PBPC collection after steady-state mobilization either with 1 x 10 mu g/kg (n = 27) or with 2 x 5 mu g/kg (n = 22) G-CSF daily for 4 consecutive days until completion of apheresis. Apheresis was started on day 5. Priming with 2 x 5 mu g/kg resulted in a higher median number of CD34(+) cells (5.8 vs 1.9 x 10(6)/kg, P = 0.003), MNC (6.6 vs 2.6 x 10(8)/kg, P < 0.001) and CFU-GM (6.5 vs 1.3 x 10(4)/kg, P = 0.001) in the first apheresis than with 1 x 10 mu g/kg. Also the overall number of collected BFU-E was higher in the 2 x 5 mu g group (9.2 vs 3.1 x 10(4)/kg; P = 0.01). After high-dose chemotherapy with cyclophosphamide/thiotepa/mitoxantrone (n = 46) hematopoietic engraftment with leukocyte count >1.0/nl was reached in both groups after a median of 10 days (range, 8-15) and with platelets count >50/nl after 12 (range, 9-40) and 13 days (range, 12-41), respectively. A threshold of >2.5 x 10(6)/kg reinfused CD34(+) cells ensured rapid platelet engraftment (12 vs 17 days; P = 0.12). Therefore, the target of collecting >2.5 x 10(6) CD34(+) cells was achieved in 21/27 (80%) patients of the 1 x 10 mu g group and in 21/22 (95%) patients of the 2 x 5 mu g/kg group with a median of two aphereses (range, 1-4). None in the 10 mu g/kg group, but 6/22 (28%) patients in the 2 x 5 mu g/kg group required only one apheresis procedure, resulting in fewer apheresis procedures in the 2 x 5 mu g/kg group (mean, 1.8 vs 2.3, P = 0.01). These results demonstrate that priming with 10 mu g/kg G-CSF alone is well tolerated and effective in mobilizing sufficient numbers of CD34(+) cells in breast cancer patients and provide prompt engraftment after CTM high-dose chemotherapy. G-CSF given 5 mu g/kg twice daily (2 x 5 mu g) leads to a higher harvest of CD34(+) cells and required fewer apheresis procedures than when given 10 mu g/kg once daily (1 x 10 mu g).