Autologous or Syngeneic Stem Cell Transplant Followed by Donor Stem Cell Transplant and Bortezomib in Treating Patients With Newly Diagnosed High-Risk, Relapsed, or Refractory Multiple Myeloma

Inclusion Criteria

• Newly diagnosed patients must have received induction therapy (e.g., vincristine, doxorubicin, dexamethasone [VAD], thalidomide/dexamethasone) for a minimum of 4 cycles
• Must have the capacity to give informed consent
• Must have an human leukocyte antigen (HLA) genotypically identical sibling or a phenotypically matched relative or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search
• In addition, patients must meet at least one of the criteria A-I (A-G at time of diagnosis or pre-autograft):
• A) Any abnormal karyotype by metaphase analysis except for isolated t(11,14) and constitutional cytogenetic abnormality
• B) Fluorescence in situ hybridization (FISH) translocation 4;14
• C) FISH translocation 14;16
• D) FISH deletion 17p
• E) Beta2-microglobulin > 5.5 mg/L
• F) Cytogenetic hypodiploidy
• G) Plasmablastic morphology (>= 2%)
• DONOR: HLA genotypically identical sibling or phenotypically matched relative OR
• DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria, Grade #2.1)
• Matched HLA-A, B, C, DRB1, and DQB1 alleles by high resolution typing.
• Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing

Exclusion Criteria

• Recurrent or non-responsive (less than partial response [PR]) MM after at least two different lines of conventional chemotherapy
• Progressive MM after a previous autograft
• Life expectancy severely limited by disease other than malignancy
• Seropositive for the human immunodeficiency virus (HIV)
• Females who are pregnant or breastfeeding
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
• Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
• Patients with the following organ dysfunction:
• Symptomatic coronary artery disease or ejection fraction 3 mg/dL; and symptomatic biliary disease;
• Karnofsky score = grade 2 peripheral neuropathy
• Patient has an active bacterial or fungal infection unresponsive to medical therapy
• DONOR: Identical twin
• DONOR: Donors unwilling to donate PBSC
• DONOR: Pregnancy
• DONOR: Infection with HIV
• DONOR: Inability to achieve adequate venous access
• DONOR: Known allergy to G-CSF
• DONOR: Current serious systemic illness
• DONOR: Failure to meet FHCRC criteria for stem cell donation
• DONOR: Age < 12 years
• DONOR: A positive anti-donor cytotoxic crossmatch
• DONOR: Patient and donor pairs must not be homozygous at mismatched allele