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 hematop oietic reconstitution can be used successfully as hematopoietic suppor t for super-dose chemotherapy. A major problem for collection of perip heral blood progenitor cells has been determination of optimal time to start leukapheresis and of the adequate amount of progenitor cells. T his study has demonstrated that an induction chemotherapy with augment ed dosage of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) in con junction with granulocyte-macrophage colony-stimulating factor (CM-CSF ) successfully mobilized peripheral blood progenitor cells in 15 patie nts with metastatic breast cancer. By monitoring the granulocyte-macro phage colony-forming units (CFU-GM), erythrocyte burst-forming units ( BFU-E), and CD34+ cells in peripheral blood daily after leukocyte nadi r, we have identified an optimal 'window' in which concentrations of b lood progenitor cells reached a maximum range. Although the time inter val between chemotherapy and the lime for maximum stimulation could va ry from between 13 days to 19 days, maximum mobilization started consi stently 2 days after the white blood cells (WBC) recovered to > 2.0 x 10(9)/l after nadir, and remained elevated for 4 to 5 days. A signific ant reduction of progenitor cells in peripheral blood and in the corre sponding leukapheresis products was observed, however, from cycle 1 ve rsus subsequent cycles (p < 0.0001), but there was no significant diff erence between cycles 2 and 3. When used as the sole source of hematop oietic support for super-dose chemotherapy with cyclophosphamide, mito xantrone, and carboplatin, these progenitor cells induce rapid and sus tained reconstitution in all patients. The median time from reinfusion to recovery of absolute neutrophil count (ANC) to > 0.5 x 10(9)/l was 13 days (range 9-18 days) and to an unmaintained platelet count of > 50 x 10(9)/l, 12 days (range 10-35 days). Autologous transplantation w ith stimulated blood progenitor cells can be an efficient alternative to bone marrow transplantation. With optimal liming for collections, a s few as two leukapheresis procedures are required to obtain an adequa te progenitor cell dose.