Summary:Fifty women with breast cancer metastatic to bone or bone marrow involvement on light microscopy at the time of initial evaluation were treated with high-dose chemotherapy (HDC) and peripheral blood progenitor cell (PBPC) transplantation with CD34؉ cell selection using the Isolex 300i system. All patients received induction chemotherapy. PBPC were mobilized with chemotherapy and granulocyte colony-stimulating factor. The median CD34+ progenitor purity was 94.7% (range 72-98.7%) and recovery 38.4% (range 21-60%). Fortyeight hours after HDC with cyclophosphamide, cisplatin and carmustine, PBPC were reinfused. Median time to neutrophil count Ͼ0.5 ؋ 10 9 /l was 9 (range 9-12) days and to platelet transfusion independence 11 (4-30) days. These data demonstrate that selected CD34 ؉ PBPCs allow rapid hematologic reconstitution after HDC. During follow-up, 23% of patients developed herpes zoster. Two patients developed cytomegalovirus infections. Three patients developed fungal infections. The development of these infections was not associated with steroid use but appeared more frequently in patients with diabetes mellitus. Seventy-four per cent of patients received steroids for pulmonary toxicity. Treatmentrelated mortality was 4%. Progression-free survival and overall survival at 35 months was 22.4% and 40.5%, with a median of 11.4 months and 15.4 months, respectively. Bone Marrow Transplantation (2001) 28, 1023-1029. Keywords: CD34; immunomagnetic separation; peripheral blood progenitor cell transplantation; metastatic breast cancer High-dose chemotherapy (HDC) and autologous hematopoietic cell transplant has been shown in both phase I and phase II studies and from registry data to achieve longer disease-free and overall survivals in women with metastatic

Summary:Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin ( Keywords: autologous; transplantation; breast cancer; doxorubicin; cardiotoxicity A previous study of the combination of doxorubicin, 5-fluorouracil and methotrexate as an induction regimen prior to HDC and PBPCT showed significant activity with a CR rate of 23% and a PR rate of 46% for an overall response of 72% in women with metastatic breast cancer. 1 While the regimen showed very good activity it also had a significant toxicity profile with mucositis being a major drawback. As a consequence we were eager to define an alternative induction regimen for use in our next generation trials of HDC with hematopoietic cell support. Paclitaxel (Taxol; BristolMeyers Squibb, Princeton, NJ, USA) was the initial taxane evaluated in the treatment of metastatic breast cancer. It was found to be an active agent both in patients who were chemotherapy naive and in those who were anthracyclineresistant. 2,3 The significant activity of paclitaxel plus the established role of doxorubicin in breast cancer, led to the logical choice of the combination of these two agents as an induction regimen. [4][5][6][7] Gianni and coworkers 8 first reported the combination of doxorubicin and a 3-h infusion of paclitaxel in 1995. They established that a significant number of women (94%) with previously untreated metastatic breast cancer responded to this combination. Unfortunately, a higher number of patients in this and subsequent studies developed cardiac arrhythmia and congestive heart failure at doxorubicin doses lower than previously reported for doxorubicin alone. 9,10 Combinations of paclitaxel with other agents have indicated that the sequence and infusion rates of the respective agents have a significant effect on the maximum tolerated dose (MTD). When paclitaxel, doxorubicin and cyclophosphamide were given in a sequential fashion rather than concurrently no increase in cardiac toxicity was observed. 11 Studies employing longer infusions of both paclitaxel and doxorubicin found a sequence-dependent difference in the dose-limiting toxicity. 12 With a short infusion of doxorubicin and a 3-h infusion of paclitaxel the MTD did not appear to be affected by the drug sequence. 8 Pharmacokinetic companion studies of this combination demonstrated

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