OBJECTIVES:

• Compare disease control and extended survival in patients with multiple myeloma when treated with either filgrastim (G-CSF) or sargramostim (GM-CSF) plus high-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation followed by interferon alfa.
• Determine whether these priming treatments induce sufficient mobilization of circulating PBSC to allow their collection by leukapheresis for subsequent use in autologous transplantation in these patients.
• Determine whether these treatments induce complete response in conjunction with rapid hematopoietic recovery and modest transplant-associated morbidity and mortality in this patient population.
• Determine whether interferon alfa, given as maintenance immunostimulatory therapy for patients achieving significant cytoreduction post transplantation, can prevent or delay malignant relapse in these patients.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

• Arm I: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day 1, mitoxantrone IV over 1 hour daily on days 1-2, and dexamethasone IV every 12 hours beginning on day 1 for a total of 4 doses. Patients also receive sargramostim (GM-CSF) IV over 2 hours or subcutaneously (SC) daily beginning 48 hours after the last dose of mitoxantrone and continuing until completion of leukapheresis. Peripheral blood stem cells (PBSC) are collected daily on days 11-13 after neutrophil recovery.
• Arm II: In the priming phase, patients receive the same treatment as in arm I except these patients receive filgrastim (G-CSF) IV over 15 minutes or SC in place of GM-CSF. In the transplant phase, patients who have not received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -6 and -5 and total body irradiation twice daily on days -3 through -1. Autologous PBSC are reinfused on day 0. Patients also receive GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes daily beginning on day 0 and continuing until day 28 or until blood counts recover.

Patients who have received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -6 through -3, carmustine IV over 1 hour on day -6, and etoposide IV over 4 hours every 12 hours for a total of 6 doses on days -6 through -4. Autologous PBSC are reinfused on day 0. Patients also receive GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes daily beginning on day 0 and continuing until day 28 or until blood counts recover.

All patients then receive interferon alfa SC 3 times weekly starting on day 28 and continuing until relapse or disease progression.

Patients may also undergo radiotherapy 5 days a week for 2 weeks for residual bony lesions measuring greater than 2 cm.

Patients are followed at days 28 and 100, and at 6, 9, 12, 18, 24, 30, and 36 months.

PROJECTED ACCRUAL: A total of 25-35 patients will be accrued for this study within 2-3 years.