Optimal timing for collections of blood progenitor cells following induction chemotherapy and granulocyte-macrophage colony-stimulating factor for autologous transplantation in advanced breast cancer

Circulating progenitor cells collected during periods of rapid hematopoietic reconstitution can be used successfully as hematopoietic support for super-dose chemotherapy. A major problem for collection of peripheral blood progenitor cells has been determination of optimal time to start leukapheresis and of the adequate amount of progenitor cells. This study has demonstrated that an induction chemotherapy with augmented dosage of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) in conjunction with granulocyte-macrophage colony-stimulating factor (CM-CSF) successfully mobilized peripheral blood progenitor cells in 15 patients with metastatic breast cancer. By monitoring the granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte burst-forming units (BFU-E), and CD34+ cells in peripheral blood daily after leukocyte nadir, we have identified an optimal 'window' in which concentrations of blood progenitor cells reached a maximum range. Although the time interval between chemotherapy and the time for maximum stimulation could vary from between 13 days to 19 days, maximum mobilization started consistently 2 days after the white blood cells (WBC) recovered to > 2.0 × 10⁹/l after nadir, and remained elevated for 4 to 5 days. A significant reduction of progenitor cells in peripheral blood and in the corresponding leukapheresis products was observed, however, from cycle 1 versus subsequent cycles (p < 0.0001), but there was no significant difference between cycles 2 and 3. When used as the sole source of hematopoietic support for super-dose chemotherapy with cyclophosphamide, mitoxantrone, and carboplatin, these progenitor cells induce rapid and sustained reconstitution in all patients. The median time from reinfusion to recovery of absolute neutrophil count (ANC) to > 0.5 × 10⁹/l was 13 days (range 9-18 days) and to an unmaintained platelet count of > 50 × 10⁹/l, 12 days (range 10-35 days). Autologous transplantation with stimulated blood progenitor cells can be an efficient alternative to bone marrow transplantation. With optimal timing for collections, as few as two leukapheresis procedures are required to obtain an adequate progenitor cell dose.