Inclusion Criteria:

- Patients must have histologically or cytologically confirmed Multiple Myeloma

- Measurable disease must be present as defined by Protein criteria (quantifiable
M-component in serum, urine or Serum Free Light Chains) in order to evaluate response
as per IMWG3. Non-secretory patients are eligible provided the patient has > 20%
plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI

- Age 18 to 72 years. Because no dosing or adverse event data are currently available
on the use of Busulfan in combination with Melphalan and Bortezomib in patients <18
years of age, children are excluded from this study but will be eligible for future
pediatric phase 2 combination trials.

- Patients must have received induction chemotherapy for myeloma, but no more than 12
months of prior chemotherapy for this disease, and must be eligible for the first
planned autologous transplant

- A minimum stem cell dose of 2.0 x 106 CD34+ cells/kg has been collected.

- Life expectancy of greater than 12 months

- ECOG performance status <2 (Karnofsky >60%; see Appendix A).

- Patients must have normal organ and marrow function as defined below:

- leukocytes >3,000/mcL (unless myeloma related)

- absolute neutrophil count >1,500/mcL (unless myeloma related)

- platelets >50,000/mcL (unless myeloma related)

- total bilirubin <2 X institutional upper limit of normal unless 2nd to Gilbert's
disease

- AST(SGOT)/ALT(SGPT) <3 X institutional upper limit of normal

- creatinine <1.5 X institutional upper limit of normal OR

- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

- Ejection fraction by ECHO or MUGA ≥ 40% performed within 60 days prior to
registration

- Patients must have adequate pulmonary function studies: > 50% of predicted on
mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted,
within 60 days of registration. If the patient is unable to complete pulmonary
function tests due to MM related pain or condition, exception may be granted if the
principal investigator (PI) documents that the patient is a candidate for high dose
therapy.

- The effects of Busulfan, Melphalan and Bortezomib on the developing human fetus at
the recommended therapeutic dose are unknown. For this reason and because alkylating
agents as well as other therapeutic agents used in this trial are known to be
teratogenic, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for at least six month following the stem cell transplantation.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.

- Prior treatment history of autologous HSCT or high-dose chemotherapy with stem cell
rescue for any medical reason, not limited to myeloma treatment

- Patients may not be receiving any other investigational agents.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to or other agents used in the study, such as busulfan, melphalan,
bortezomib, boron, or mannitol

- Grade 2 or greater peripheral neuropathy within 14 days prior to enrollment

- Unresolved grade >/= 3 non-hematologic toxicity from previous therapy. Patients with
grade 2 toxicity will be eligible at the discretion of the PI.

- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
in situ. Cancer treated with curative intent < 5 years will not be allowed unless
approved by the principal investigator (PI). Cancer treated with curative intent > 5
years will be allowed.

- Patients must not have significant co-morbid medical condition

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements. Patients must not have suffered recent (< 6 months) myocardial
infarction, unstable angina, difficult to control congestive heart failure,
uncontrolled hypertension, or difficult to control cardiac arrhythmias.

- Pregnant women are excluded from this study because Busulfan, melphalan and
bortezomib Class D agents with the potential for teratogenic or abortifacient
effects. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with the study agent
breastfeeding should be discontinued if the mother is treated with Busulfan.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with Busulfan. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

- Patients found to have an active hepatitis B infection (hepatitis B surface antigen
+) are not eligible unless they meet ONE of the following criteria:

- Patient is able to start dual anti-Hep B therapy prior to enrollment with adefovir
and telbivudine

- Patient is already on dual anti-hepatitis B therapy

- Consultation and co-management with a hepatitis expert regarding hepatitis B
treatment is strongly encouraged before and during the trial.

- Patients, who are positive for Hepatitis B core antibody, but negative for the
Hepatitis B surface antigen, should be started on lamivudine 100mg daily until at
least 3 months post stem cell transplant