OBJECTIVES:

• Determine the incidence of early mortality in patients with multiple myeloma treated with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation.
• Determine the incidence of early allogeneic graft failure (before day 100 after allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host disease (GVHD) in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the overall and disease-free survival of patients treated with this regimen.
• Correlate changes in the T-cell population with clinical outcome, such as survival, in patients treated with this regimen.
• Correlate changes in the T-cell population with the incidence of GVHD, use of immunosuppressive agents, and effects of fludarabine in patients treated with this regimen.
• Determine the degree of chimerism after allogeneic PBSC transplantation and the time course over which it is established in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation, patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis, beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total 19-46 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma meeting 1 of the following criteria:

  • Bone marrow plasmacytosis with at least 10% plasma cells
  • Sheets of plasma cells
  • Biopsy-proven plasmacytoma

• Meets at least 1 of the following criteria:

  • Presence of myeloma (M)-protein in the serum
  • Presence of M-protein in the urine

  • Radiographic evidence of osteolytic lesions

    • Generalized osteoporosis allowed if at least 20% plasma cells in bone marrow

• No non-secretory myeloma

  • Prior M-protein in serum or urine allowed provided patient is now in complete remission
• Must be receiving conventional-dose chemotherapy as initial therapy or as salvage therapy
• Must have HLA-A, -B, and -DR genotypically identical sibling donor

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• AST no greater than 3 times upper limit of normal
• Bilirubin less than 2.0 mg/dL

Renal:

• Not specified

Cardiovascular:

• LVEF greater than 40% at rest if symptomatic cardiac disease is present

Pulmonary:

• DLCO greater than 50% of predicted (corrected for hemoglobin) if symptomatic pulmonary disease is present

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior autologous or allogeneic peripheral blood stem cell or bone marrow transplantation

Chemotherapy:

• See Disease Characteristics
• More than 28 days since prior chemotherapy (including primary chemotherapy for hematopoietic stem cell collection)
• No other concurrent cytotoxic chemotherapy between autologous and allogeneic transplantation

Endocrine therapy:

• Prior dexamethasone or other corticosteroids allowed
• Concurrent corticosteroids between autologous and allogeneic transplantation allowed

Radiotherapy:

• Concurrent radiotherapy between autologous and allogeneic transplantation allowed

Surgery:

• Not specified