HIGH-DOSE ETOPOSIDE-BASED MYELOABLATIVE THERAPY FOLLOWED BY AUTOLOGOUS BLOOD PROGENITOR-CELL RESCUE IN THE TREATMENT OF MULTIPLE-MYELOMA

BACKGROUND. A number of studies have demonstrated that high dose chemo therapy, with or without radiotherapy, with autologous marrow and/or p eripheral blood progenitor cell support can result in improved overall and complete response rates in patients with multiple myeloma, and a minority of patients become long term survivors. Based on their favora ble experience with high dose etoposide-based regimens in patients wit h Hodgkin's disease and non-Hodgkin's lymphoma, the authors explored t he use of these regimens prior to autologous progenitor cell rescue in patients with multiple myeloma. METHODS. Thirty-four patients (median age, 49 years; range, 38-65) with multiple myeloma who were responsiv e to standard chemotherapy were enrolled in this study. Blood progenit or cells were collected after treatment with cyclophosphamide at a dos e of 4 g/m(2) followed by granulocyte-colony stimulating factor (G-CSF ) at a dose of approximately 10 mu g/kg/day subcutaneously, and the co llection continued daily until the target number of mononuclear cells had been obtained. The preparative regimen consisted of fractionated t otal body irradiation (FTBI) of 1200 centigray in 10 fractions on Day -8 to Day -5, etoposide 60 mg/kg intravenously (i.v.) on Day -4, and c yclophosphamide 100 mg/kg i.v. on Day -2. Day 0 was the day of progeni tor cell infusion. Patients who were older than 50 years or had receiv ed prior radiation therapy that precluded FTBI received carmustine 15 mg/kg i.v. or lomustine 15 mg/kg orally on Day -6 rather than FTBI. G- CSF (5 mu g/kg/day) was begun the day after progenitor cell infusion a nd continued until engraftment. RESULTS. Recovery of granulocytes to 5 00/mu L occurred at a median of 9 days (range, 7-13), and platelet rec overy to 20,000/mu/L occurred without transfusion at 9 days (range, 6- 88) after progenitor cell infusion. Thirty-two patients were evaluable for response. Eleven patients (34%) achieved a complete remission, 17 (53%) achieved a partial remission, and 4 (13%) had stable disease fo llowing high dose therapy and progenitor cell rescue. The actuarial ev ent free survival at 4 years for the entire group was 26%, and overall survival was 36%. The median time to progression of disease was 13 mo nths (range, 2-42). Two patients died of regimen-related toxicity, one of venoocclusive disease of the liver and the other of multiorgan fai lure. In a multivariate analysis, only the extent of prior therapy was a significant prognostic factor for event free survival, and no signi ficant factors were identified for overall survival. CONCLUSIONS. High dose etoposide-based myeloablative regimens followed by autologous bl ood progenitor cell rescue are relatively well tolerated and effective for the treatment of multiple myeloma, and a minority of patients bec ome long term disease free survivors. (C) 1996 American Cancer Society .