• Progression-free survival at 1 year [ Designated as safety issue: No ]
• Treatment-related mortality at 100 days [ Designated as safety issue: No ]
• Acute graft-versus-host disease grades III-IV [ Designated as safety issue: No ]

• Progression-free survival at 1 year
• Treatment-related mortality at 100 days
• Acute graft-versus-host disease grades III-IV

RATIONALE: Stem cell transplantation may be able to replace immune cells that were destroyed by previous cancer treatment. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Cyclosporine and mycophenolate mofetil may prevent this from happening.

PURPOSE: This phase I/II trial is studying donor stem cell transplantation to see how well it works in treating patients with multiple myeloma that has been previously treated.

OBJECTIVES:

• Determine the efficacy of allogeneic hematopoietic stem cell transplantation, in terms of 1-year progression-free survival and overall survival, in patients with previously treated multiple myeloma.
• Determine non-relapse mortality at day 100 in patients treated with this regimen.
• Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes on days -5 to -3 and melphalan IV over 15-20 minutes on day -2. Patients undergo total body irradiation and allogeneic hematopoietic stem cell transplantation on day 0.

Patients also receive graft-versus-host disease prophylaxis according to the type of donor.

• Related donor: Patients receive oral cyclosporine every 12 hours on days -3 to 80 followed by a taper until day 180 and oral mycophenolate mofetil every 12 hours on days 0-27.
• Unrelated donor: Patients receive oral cyclosporine every 12 hours on days -3 to 100 followed by a taper until day 177 and oral mycophenolate mofetil every 8 hours on days 0-40 followed by a taper until day 96.

Patients are followed at days 28, 56, and 84; at months 6, 12, 18, and 24; and then annually for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

• Biological: therapeutic allogeneic lymphocytes
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: melphalan
• Drug: mycophenolate mofetil
• Procedure: peripheral blood stem cell transplantation
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

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

  • Progressive disease after at least 1 prior syngeneic or autologous hematopoietic stem cell transplantation (indicated by greater than 25% increase in serum or urine paraprotein levels or appearance of new lytic bone lesions or plasmacytomas)
  • Unable to collect autologous peripheral blood stem cells due to poor marrow reserve OR contraindications to undergoing stem cell mobilization and has progressive disease after at least 4 prior courses of standard chemotherapy (e.g., dexamethasone/doxorubicin/vincristine)

• Availability of 1 of the following donors:

  • HLA genotypically matched identical sibling
  • HLA phenotypically matched relative

  • HLA phenotypically matched unrelated donor

    • Matched for serologically recognized HLA-A or B or C antigens and at least 5/6 HLA-A or B or C alleles
    • Matched for HLA-DRB1 and DQB1 alleles
  • No identical twins

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No chronic viral hepatitis with bilirubin > 3 mg/dL
• No biliary obstruction
• No symptomatic biliary disease
• No ascites related to portal hypertension
• No bridging fibrosis
• No bacterial or fungal liver abcess
• No fulminant liver failure
• No cirrhosis of liver with evidence of portal hypertension
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• No uncorrectable hepatic synthetic dysfunction evidenced by prolonged PT
• SGPT and SGOT no greater than 4 times ULN
• No alcoholic hepatitis
• No hepatic encephalopathy

Renal

• Creatinine clearance at least 40 mL/min

Cardiovascular

• LVEF at least 40%
• No symptomatic heart failure
• No poorly controlled hypertension

Pulmonary

• DLCO at least 50%
• No requirement for continuous supplemental oxygen

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation
• HIV negative
• Cytomegalovirus (CMV)-antigenemia negative
• No impaired capacity that would preclude informed consent
• No persistent mucositis or gastrointestinal symptoms requiring hyperalimentation and/or IV hydration
• No prior or concurrent esophageal varices
• No nonhematologic malignancy within the past 5 years except nonmelanoma skin cancer currently in complete remission wtih ≤ 20% risk of recurrence
• No active nonhematologic malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent steroids for autologous or syngeneic graft-versus-host disease

Radiotherapy

• No other concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 2 weeks since prior ganciclovir or foscarnet for previous CMV reactivation/infection
• No concurrent ganciclovir or foscarnet for previous CMV reactivation/infection
• No concurrent IV antibiotics for active infections
• No concurrent bisphosphonates during and for 30 days after transplantation