The goal of this study is to evaluate the safety of melphalan and autologous PBSCT (peripheral blood stem cell transplantation - stem cells that come from your own body) in combination with bortezomib, a new FDA approved drug used to treat myeloma.

Inclusion Criteria:

• Patients with multiple myeloma who are eligible for an autologous peripheral blood progenitor transplant
• Male and female subjects between the age of 18 and 70 years.
• Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care
• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subjects agrees to use an acceptable method for contraception for the duration of the study.
• Biopsy proven diagnosis of multiple myeloma from bone marrow aspirate and biopsy prior to study initiation
• Patient has achieved less than 90% disease reduction from previous treatment prior to transplant (as measured by serum or urine protein electrophoresis) and has more than 5% plasma cells in the bone marrow, or patient has progressed and has more than 5% plasma cells in the bone marrow.
• Karnofsky Performance Status score of ≥ 60%
• Patient has met the following laboratory requirements prior to Day -4
• Platelet count ≥ 50, 000/mm3
• Absolute Neutrophil Count ≥ 500/mm3
• Hemoglobin ≥ 10 g/dL (transfusion allowed to meet this criterion)
• Calculated creatinine clearance ≥ 30mL/min
• Toxic effects of previous therapy or surgery resolved to Grade 2 or better

Exclusion Criteria:

• Unsupportable anemia with < 10b/dL
• Patient has a calculated or measured creatinine clearance of < 30mL/min within 14 days before enrollment
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
• Patient has hypersensitivity to bortezomib, boron or mannitol
• Patient has had an allergic reaction to melphalan or chlorambucil
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-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 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Cardiac or pulmonary dysfunction such that patients do not meet institutional pre-transplant evaluation criteria
• Known central nervous system involvement or suspicion of involvement with Myeloma
• Other active malignancies (with the exception of basal and squamous cell skin cancer) within 5 years of study entry. Patients with treated prostate or cervical cancer in situ who are 2 or more years from therapy and remain free of disease may be entered into the study at the investigator's discretion.
• Known to be HIV positive, HIV-1 positive