Stem cell mobilization with G-CSF alone in breast cancer patients: higher progenitor cell yield by delivering divided doses (2 × 5 μg/kg) compared to a single dose (1 × 10 μg/kg)

Abstract

We investigated the schedule dependency of G-CSF (10 μg/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, ⩾10+ Ln n = 36; locally advanced/ inflammatory n = 8, stage IV (NED) n = 5) underwent PBPC collection after steady-state mobilization either with 1 × 10 μg/kg (n = 27) or with 2 × 5 μg/kg (n = 22) G-CSF daily for 4 consecutive days until completion of apheresis. Apheresis was started on day 5. Priming with 2 × 5 μg/kg resulted in a higher median number of CD34⁺ cells (5.8 vs 1.9 × 10⁶/kg, P = 0.003), MNC (6.6 vs 2.6 × 10⁸/kg, P < 0.001) and cfu-gm (6.5 vs 1.3 × 10⁴/kg, P = 0.001) in the first apheresis than with 1 × 10 μg/kg. Also the overall number of collected BFU-E was higher in the 2 × 5 μg group (9.2 vs 3.1 × 10⁴/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 × 10⁶/kg reinfused CD34⁺ cells ensured rapid platelet engraftment (12 vs 17 days; P = 0.12). Therefore, the target of collecting >2.5 × 10⁶ CD34⁺ cells was achieved in 21/27 (80%) patients of the 1 × 10 μg group and in 21/22 (95%) patients of the 2 × 5 μg/kg group with a median of two aphereses (range, 1–4). None in the 10 μg/kg group, but 6/22 (28%) patients in the 2 × 5 μg/kg group required only one apheresis procedure, resulting in fewer apheresis procedures in the 2 × 5 μg/kg group (mean, 1.8 vs 2.3, P = 0.01). These results demonstrate that priming with 10 μg/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 μg/kg twice daily (2 × 5 μg) leads to a higher harvest of CD34⁺ cells and required fewer apheresis procedures than when given 10 μg/kg once daily (1 × 10 μg).