RATIONALE: Giving melphalan and bortezomib before and after a stem cell transplant stops the growth of abnormal cells by stopping them from dividing or killing them. Giving colony-stimulating factors and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy and monoclonal antibody therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase II trial is studying how well giving melphalan together with bortezomib followed by stem cell transplant works in treating patients with primary systemic amyloidosis.

OBJECTIVES:

• To determine if hematologic responses to high-dose melphalan and autologous stem cell transplantation increase with addition of bortezomib in the conditioning regimen in patients with primary systemic amyloidosis.

OUTLINE:

• Autologous stem cell mobilization and collection: Patients receive filgrastim to mobilize stem cells, which are then collected.
• Conditioning regimen: Patients receive bortezomib intravenously on days -6, -3, 1, and 4 and oral high-dose melphalan on days -2 and -1.
• Stem cell transplantation: Patients undergo autologous stem cell transplantation on day 0.

After completion of study therapy, patients are followed every 6 months for 1 year and annually thereafter.

Inclusion criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed primary systemic amyloidosis based on the following criteria:

  • Amyloid light-chain disease
  • Deposition of amyloid material by congo red stain showing characteristic green birefringence
  • Monoclonal light chain protein (Bence Jones protein) in the serum or urine, immunohistochemical studies, or serum free light chain assay
  • Evidence of tissue involvement other than carpal tunnel syndrome (i.e., positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells); tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations

PATIENT CHARACTERISTICS:

• Southwest Oncology Group performance status 0-1
• Fertile patients must use effective contraception
• Left ventricular ejection fraction ≥ 45% by Echocardiogram within the past 60 days
• diffusion capacity of lung for carbon monoxide ≥ 50%

PRIOR CONCURRENT THERAPY:

• Prior chemotherapy with alkylating agent allowed provided there is no morphological or cytogenetic evidence of myelodysplastic syndromes
• Prior total cumulative dose of oral melphalan < 300 mg
• At least 4 weeks since prior cytotoxic therapy and fully recovered

Exclusion criteria:

• No senile, secondary, localized, dialysis-related, or familial amyloidosis

• No overt multiple myeloma (> 30% of bone marrow plasmacytosis, extensive [> 2] lytic lesions, or hypercalcemia)

• Not pregnant or nursing

• No myocardial infarction within the past 6 months, congestive heart failure, or arrhythmia refractory to therapy

• No prior malignancy except for any of the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • In situ cervical cancer
  • Adequately treated stage I or II cancer currently in complete remission
  • Any cancer from which the patient has been disease-free ≥ 5 years

• No advanced (grade 3-4) pre-existing neuropathy

• No HIV positivity

1 year