OBJECTIVES:

• Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.
• Determine the response rate and progression-free and overall survival of patients treated with this regimen.
• Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in patients who are not in complete remission (CR) 6 months after the second course of high-dose chemotherapy.
• Determine whether administration of thalidomide can increase the CR rate in patients who are not in CR 6 months after the second course of high-dose chemotherapy and determine its effect on progression-free and overall survival of these patients.
• Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the pharmacokinetics with the toxic effects of these drugs and outcome in these patients.
• Determine the effect of thalidomide on microvascular density of bone marrow and correlate these possible effects with outcome in these patients.
• Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization in baseline and post treatment bone marrow and blood specimens and correlate the presence/persistence of these features with treatment outcome in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.

Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is administered IV or SC daily beginning on day 1 and continuing until blood counts recover. Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day 0 and G-CSF is administered IV or SC daily until blood counts recover.

Patients with responding or stable disease after chemotherapy receive maintenance therapy with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy. Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive pamidronate IV every 4 weeks until disease progression. Patients who are not in complete remission (CR) 6 months after completing the second course of chemotherapy receive oral thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within approximately 2.5 years.

DISEASE CHARACTERISTICS:

• Histologically proven stage I-III multiple myeloma

  • Less than 18 months since diagnosis

  • Smoldering myeloma allowed if there is evidence of progressive disease requiring therapy

    • At least 25% increase in M protein levels or Bence Jones excretion
    • Hemoglobin no greater than 10.5 g/dL
    • Hypercalcemia
    • Frequent infections
    • Rise in serum creatinine above normal on 2 separate occasions
  • Nonquantifiable monoclonal proteins allowed if other criteria for multiple myeloma or smoldering myeloma are met

• Response/status after induction therapy:

  • Responding or stable disease AND no greater than 40% myelomatous involvement of bone marrow
• No Waldenstrom's macroglobulinemia

PATIENT CHARACTERISTICS:

Age:

• 65 and under

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT less than 2.5 times upper limit of normal
• Hepatitis B antigen or hepatitis C RNA negative

Renal:

• See Disease Characteristics
• Creatinine no greater than 1.4 mg/dL
• Creatinine clearance greater than 65 mL/min

Cardiovascular:

• Cardiac ejection fraction at least 50% by MUGA or echocardiogram

Pulmonary:

• FEV_1 greater than 60%
• DLCO greater than 50% of predicted lower limit

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other medical or psychosocial problems that would increase patient risk
• No other malignancy within past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No known hypersensitivity to filgrastim (G-CSF) or E. coli-derived proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified