PHASE-II STUDY OF HIGH-DOSE BUSULFAN, MELPHALAN AND THIOTEPA WITH AUTOLOGOUS PERIPHERAL-BLOOD STEM-CELL SUPPORT IN PATIENTS WITH MALIGNANT DISEASE

The purpose of this study was to determine the toxicities and potentia l effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Me/T T) followed by autologous peripheral blood stem cell (PBSC) infusion i n patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m(2)) and TT (500 mg/m(2)) followed by PBSC i nfusion in 104 patients with breast cancer (n = 48), malignant lymphom a (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and othe r malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Gr ade 3-4 regimen-related toxicities occurred in 14% of patients, causin g regimen-related mortality in six (6%) patients with an overall trans plant-related mortality of 9%. Transplant-related deaths occurred in 6 /62 patients (10%) treated in an academic medical center and in 3/42 ( 7%) treated in a community cancer center. Complete remissions (CR) wer e achieved in 1/17 (6%) patients with refractory stage IV breast cance r, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) wit h more-advanced lymphoma and 4/4 with less-advanced lymphoma. These pa tients are alive and disease-free a median of 712, 279, 461 and 404 da ys after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 day s after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regi men followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in pati ents with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have signific ant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.