Melphalan, Bortezomib, and Stem Cell Transplant 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