THE USE OF PERIPHERAL-BLOOD HEMATOPOIETIC PROGENITORS MOBILIZED WITH STANDARD-DOSE CHEMOTHERAPY PLUS GRANULOCYTE-COLONY-STIMULATING FACTOR TO SUPPORT MULTICYCLIC DOSE-INTENSIVE CHEMOTHERAPY FOR ADVANCED BREAST-CANCER

This study was aimed at determining: (a) the degree of mobilization of peripheral blood hematopoietic progenitors (PBSC) induced by a single course of standard-dose chemotherapy (CT) followed by G-CSF and the feasibility and safety of the administration of multiple courses of intensified CT with repeated PBSC reinfusions; (b) the relationship between the number of mononuclear cells (MC) in S-phase of the cell cycle (as evaluated by DNA flow cytometry, FCM), the CRT-GM and the CD34(+) cells in the leukapheresis product. Six patients with metastatic breast cancer received a course of standard FEC (5-FU 600 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide, CTX, 600 mg/m(2), day 1) followed by G-CSF (5 mu g/kg twice a day, from day 3 until leukapheresis), which served as both initial treatment for their disease as well as the PBSC mobilization technique. Collected PBSC were fractionated and reinfused, without G-CSF, following each of further 5 subsequent intensified FEC (HD-FEC: 5-FU 750 mg/m(2), epirubicin 100 mg/m(2), CTX 1,000 mg/m(2)) courses planned at 21-day intervals. The individual hematopoietic reconstitution curves showed superimposable profiles for all patients, and the leukaphereses were performed between days 7 and 10 after the first CT course. A median of 18.8x10(9) (10.4-35.6) MC, 9.3 (2.6-23.3) CD34(+) cells x 10(6)/kg body weight and 9.8 (1.6-27.3) CFU-GM x 10(4)/kg body weight were collected from each patient (with 1 or 2 phereses). All patients received the planned 5 courses of HD-FEC followed by PBSC reinfusion, without experiencing haematological cumulative toxicity >WHO grade 3 for WBC and >grade 2 for PLT. No >grade 3 non-hematological toxicity was recorded. There were no treatment-related delays in CT administration so that the delivered average relative dose-intensity (ARDI) was 1.65. A good correlation was seen between the percentage of MC in S-phase and the number of CFU-GM (R(2)=0.566, p<0.0065) or the number of CD34(+) cells (R(2)=0.625, p<0.0031) in the leukapheresis product. A single course of standard FEC+G-CSF is effective in mobilizing sufficient amounts of PBSC to support 5 additional courses of HD-FEC, which could represent an alternative to single, myelo-suppressive CT programs. DNA analysis by FCM should be further investigated as a rapid method for PBSC quantification, since proliferating MC and CFU-GM were closely related.