RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. An autologous stem cell transplant may be able to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide followed by an autologous stem cell transplant works in treating patients with multiple myeloma.

OBJECTIVES:

Primary

• To compare relapse-free survival and overall survival of patients with multiple myeloma treated with IV busulfan vs historical control patients treated with oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation.

Secondary

• To compare pulmonary toxicity rates of IV busulfan vs oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation.

OUTLINE: Patients receive high-dose busulfan IV every 6 hours on days -8 to -4 and high-dose cyclophosphamide IV over 4 hours on days -3 and -2. Patients undergo autologous hematopoietic stem cell transplantation on day 0.

After completion of study treatment, patients are followed up periodically.

INCLUSION CRITERIA:

• Patients with a diagnosis of plasma cell myeloma
• Patients with cardiac ejection fraction >= 45% or clearance by Cleveland Clinic Faculty (CCF) cardiologist
• Patients with diffusion capacity of carbon monoxide (DLCO) >= 45% predicted or clearance by CCF pulmonologist
• Patient with previously harvested peripheral blood progenitor cells with a minimum of 2 x 10^6 CD 34+ cells/kg harvested

EXCLUSION CRITERIA:

• Patients receiving total body irradiation
• Non-myeloablative/reduced-intensity conditioning
• Pregnant and breast feeding patients
• Human immunodeficiency virus (HIV) positive
• Patients with serum creatinine > 2.0
• Prior Hematopoietic Stem Cell (HSC) transplant