• Immune T-cell depletion as measured by CD 4 count following induction chemotherapy (pre-transplant) [ Designated as safety issue: No ]
  
• Efficacy of conventional chemotherapy in patients with multiple myeloma measured by M-protein in serum, plasma cell percentage in bone marrow, 24 hour urine for urinary protein excretion, and skeletal survey at pre-transplant and 28 days post-transplant [ Designated as safety issue: No ]
  
• Treatment related morbidity and mortality as measured by the number and severity of serious adverse events and death at 100 days, 1 and 2 years post-transplant [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Determine whether cellular and humoral immunity against the unique idiotype expressed by the patient's myeloma can be induced in allogeneic peripheral blood stem cell (PBSC) donors and the recipients with multiple myeloma.
• Determine if antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic PBSC transplantation recipient in the setting of a nonmyeloablative conditioning regimen.
• Determine the effect of fludarabine, etoposide, doxorubicin, and vincristine followed by cyclophosphamide and prednisone on host T-cell depletion and myeloid depletion prior to allogeneic PBSC transplantation in these patients.
• Determine the efficacy of this chemotherapy regimen in these patients.
• Determine the treatment-related morbidity and mortality in patients treated with this regimen.
• Determine if the revaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of these patients.

OUTLINE:

Patients

• Plasmapheresis and Initial Bone Marrow: Patients undergo plasmapheresis and a bone marrow aspirate to obtain starting material for the isolation of idiotype protein (Id) needed to create the vaccine.
• Induction Chemotherapy: During the 1 to 3 months needed to generate the vaccine, patients receive fludarabine IV over 30 minutes and etoposide, doxorubicin, and vincristine IV continuously on days 1-3. Patients also receive cyclophosphamide IV over 30 minutes on day 4, oral prednisone daily on days 1-4, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Treatment repeats every 3 weeks for a maximum of 5 courses in patients with greater than 50 CD4 cells/mm^3 and in the absence of unacceptable toxicity. Patients experiencing disease progression proceed to the transplantation preparative regimen regardless of CD4 counts. Patients with less than 50 CD4 cells/mm^3 after induction chemotherapy whose donor stem cells are not yet available for transplantation may receive bortezomib IV on days 1, 4, 8, and 11. Treatment with bortezomib repeats every 3 weeks for up to 3 courses or until donor stem cells are available for transplantation.
• Transplantation Preparative Chemotherapy: At least 22 days from completion of induction chemotherapy, patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3.
• Graft-vs-Host Disease Prophylaxis: Beginning on day -1, some patients receive cyclosporine IV over 1 hour or orally every 12 hours until day 180 and methotrexate IV over 15 minutes on days 1, 3, 6, and 11.
• Transplantation: Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0.
• Vaccination: Patients are vaccinated with Id conjugated to keyhole limpet hemocyanin (KLH) SC followed by sargramostim (GM-CSF) SC in the same location at 3, 4, and 6 months post-PBSC transplantation.

Patients are followed at 6, 9, 12, 18, and 24 months.

Donors

• PBSC collection: Ten weeks before PBSC collection, donors receive Id-KLH SC on weeks 0, 2, and 6. After Id injection, donors receive GM-CSF SC in the same location. Five to seven days before PBSC collection, donors receive G-CSF SC until collection is completed. PBSC collection takes place on week 10.

Donors are followed every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 10-69 patients will be accrued for this study within 2 years.