OBJECTIVES: I. Determine engraftment of HLA identical peripheral blood stem cell allografts given after conditioning with total body irradiation and postgrafting immunosuppression with cyclosporine/mycophenolate mofetil in patients with multiple myeloma initially cytoreduced with high dose melphalan.

II. Determine disease free survival of these patients at day 100 post allografting. III. Determine the efficacy of this regimen in terms of long term progression free survival of these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1-2 hours on day 1, paclitaxel IV over 4 hours on day 2, and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 3 and continuing until the end of leukapheresis. Autologous peripheral blood stem cells (PBSC) are collected over 3-4 days and selected for CD34+ cells. Patients receive melphalan IV on day -2 (which is at least 31 days after paclitaxel), then autologous CD34+ PBSC are reinfused on day 0.

G-CSF SQ or IV is administered beginning on day 0 and continuing until blood counts recover. About 40-120 days after autografting, patients receive cyclosporine IV twice a day on days -1 and 0, then orally on days 1-56 and oral mycophenolate mofetil twice a day on days 0-27. Patients undergo total body irradiation on day 0, followed by infusion of unmodified donor PBSC. At days 28 and 56, patients are evaluated for lymphoid and myeloid chimerism.

Patients with stable mixed chimerism on day 56 without graft versus host disease receive nonmobilized donor lymphocyte infusion (DLI) over 30 minutes on day 65. Patients may receive up to 4 DLI's. Patients are followed weekly until day 90 after the last T-cell infusion, then at 4 and 6 months, then every 6 months for 1.5 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued within 4 years.