The purpose of this study is to evaluate the effectiveness of Bortezomib when added to standard chemotherapy medicine(s) for treatment of Multiple Myeloma.

The primary objectives of this study are:

• To determine the 2 year-progression free survival in multiple myeloma with an allogeneic transplant using a conditioning regimen of melphalan + fludarabine + Bortezomib in patients < 60 years of age and available HLA-matched donor and compare it with the 2 year-progression-free-survival after an autologous stem cell transplant with melphalan+Bortezomib conditioning in patients < 60 years.
• To determine the 2 year-progression free survival in multiple myeloma with an autologous stem cell transplant using a conditioning regimen of melphalan + Bortezomib. for patients > 60 years of age and patients < 60 years of age who decline allogeneic stem cell transplant.

The secondary objectives of this study are:

• To determine the overall survival in multiple myeloma with autologous or allogeneic stem cell transplants using the above conditioning regimens
• To determine the response rates in multiple myeloma using the above regimens.
• To determine minimal residual disease status using allele specific oligonucleotides (ASO-PCR) by PCR and flow-cytometry for multiple myeloma cells.
• To correlate minimal residual disease status with 2 year progression free survival and overall survival.
• To determine the incidence of acute and chronic graft-versus-host disease (GVHD) in multiple myeloma with allogeneic stem cell transplant using the above conditioning regimen.
• To examine quality of life in patients treated with allogeneic and autologous stem cell transplants using the above conditioning regimen.

Inclusion Criteria:

Multiple Myeloma Criteria(International Uniform Response Criteria for Multiple Myeloma)

• Patients with responsive disease after any line of induction therapy
• A complete response
• A very good partial response
• A partial response
• Patients greater than or equal to 18 years of age are eligible. There is upper age limit of 60 years for allogeneic transplants.
• Patients must have a histologically confirmed diagnosis.
• All patients should have a life expectancy of at least 12 weeks.
• Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance.
• Meet the following criteria for allogeneic hematopoietic cell transplant:
• Must have an identified donor match defined as: HLA-A, HLA-B, HLA- C, DRB1 8/8 allele matched sibling, family member, or unrelated donor. [7/8 would go on separate mismatched trials] and be < 60 years of age.
• Calculated hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3

Exclusion Criteria:

• Patients who do not achieve at least a partial response (PR) by the criteria mentioned above with induction therapy.
• Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.
• Patient has >/= Grade 2 peripheral neuropathy within 30 days before enrollment.
• Patient has an absolute neutrophil count of <1.0 x 10^9/L within 30 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant in order for the subject to be considered eligible. Left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) scan < 40%.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 30 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with a diffusing capacity of lung for carbon monoxide (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible.
• Patients with a total bilirubin greater than 2.0 mg/dL excluding Gilbert's syndrome and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
• Calculated creatinine clearance </= 30 ml/min within 30 days before enrollment
• Patients with active infections are ineligible.
• Patients who are HIV positive are ineligible.
• Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
• Patients with uncontrolled insulin-dependent diabetes mellitus defined as a random glucose level of > 400 in the 30 days prior to initiation of study therapy; or uncompensated major thyroid or adrenal dysfunction are ineligible.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of >/= 2(Karnofsky < 50%) are ineligible.
• Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to bone pain, may be enrolled.
• Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to a potentially reversible disease-related problem, may be enrolled.
• Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease >/= 5 years after the treatment for the cancer was completed.