Bone Marrow Transplantation, (1998) 22 , 845–851  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http:/ / www.stockton-press.co.uk/ bmt Mobilization of peripheral blood progenitor cells after induction chemotherapy (THP-doxorubicin-vinorelbine-cyclophosphamide- fluorouracil) and granulocyte colony-stimulating factor in breast cancer S Charrier, J Chassagne, H Cure ´, JO Bay, Y Communal, G Portefaix, JP Ferrie `re, G Be ´tail, R Plagne and P Chollet Centre Jean Perrin and INSERM U484, Clermont-Ferrand, France Summary: In order to evaluate the mobilization of peripheral blood progenitor cells (PBPC) after an effective induc- tion regimen in breast cancer, we performed a study on 15 breast cancer patients. Between January 1995 and June 1996, these patients received TNCF (THP-doxoru- bicin, vinorelbine, cyclophosphamide, fluorouracil for four days, every 21 days) with G-CSF support (5 g/kg for 10 days after chemotherapy) to reduce aplasia. This regimen is known to result in a complete pathological response in 30% of patients. Between two cycles of TNCF treatment, hematological recovery was observed. Progenitor cells (CFU-GM and CD34  cells) and mono- nuclear cells in DNA synthesis (MCDS) counts were performed daily, between the 12th and 17th post- chemotherapy days (81 samples). The results showed a similarity for hematological recovery and PBPC mobil- ization kinetics depending on the number of treatment cycles. The three methods used for PBPC evaluation were well correlated (P  0.01) with an optimal mean PBPC recruitment by the last day of G-CSF adminis- tration: respectively, 11 520 (1729–26 539) CFU-GM/ml of blood, 249 (14–1160) CD34  cells/l of blood and 211 (21–554) MCDS/l of blood. These results suggested that a daily injection of G-CSF after one or two TNCF cycles will produce an effective PBPC mobilization in comparison with currently used regimens. Keywords: breast cancer; TNCF induction chemo- therapy; hematological recovery; PBPC mobilization Over the past two decades, systemic chemotherapy has been used as primary treatment in locally advanced or inflammatory breast cancer making breast-conserving sur- gery possible. 1,2 Furthermore, complete clinical or patho- logical response after induction treatment results in a better individual prognosis in terms of disease-free and overall survival. 3–5 Correspondence: Dr S Charrier, Laboratoire d’Immunologie, Centre Jean Perrin, 58 rue Montalembert, BP 392, 63011 Clermont-Ferrand Cedex 1, France Received 31 March 1998; accepted 3 July 1998 Since 1990, in order to increase the response rate, and based on our previous AVCF (doxorubicin, vincristine, cyclophosphamide, fluorouracil), 6 we developed a new cytotoxic regimen, 7 using a combination of THP-doxo- rubicin, vinorelbine, cyclophosphamide and fluorouracil (TNCF). Considering its lower cardiac toxicity, the ana- logue THP-doxorubicin replaced the mother compound 8 and vinorelbine replaced vincristine because of its high response rate in metastatic breast cancer 9 (40% response as first-line treatment). This schedule was applied at the maximally tolerated dose with colony-stimulating factor (CSF) support to reduce the anticipated neutropenia. For the first 50 patients treated in the primary setting this regi- men induced a severe, but not life-threatening, hematolog- ical toxicity as expected, but also resulted in a high com- plete clinical (51%) and pathological response (30% vs 10% with most standard protocols 10,11 ). This protocol was also used in young metastatic patients for its efficacy. We postulate that this efficient TNCF regimen could reach optimal efficacy with an increasing dose. However, in this case, isolated CSF administration would not be suf- ficient for hematological recovery and further support by autologous peripheral blood progenitor cells (PBPC) would be necessary. 12–14 Chemotherapy, with or without the addition of CSF, has been used successfully to mobilize progenitor cells into the peripheral blood of cancer patients. 15–17 The most fre- quently used drugs to recruit PBPC were cyclophospham- ide plus or minus etoposide and cisplatin. 18,19 Etoposide is not a classical drug for breast cancer. Therefore, it appeared interesting to mobilize with TNCF treatment, whose effi- cacy and specificity in breast cancer has been demonstrated, although a study of its mobilization capacity has not been done. Here, we performed a study of the kinetics of mobil- ization of PBPC and the regeneration of more mature cells in peripheral blood after TNCF. We also studied whether PBPC mobilization was sufficient to allow subsequent autografts. For this purpose, in 15 patients treated by TNCF regi- men, PBPC mobilization was studied for six days, begin- ning when leukocytes were higher than 1.0  10 9 /l of blood. Analysis included leukocyte, red blood cell and plat- elet counts. PBPC were evaluated by the colony-forming units granulocyte–macrophage assay (CFU-GM), CD34 +