Inclusion Criteria

- INCLUSION CRITERIA:

MULTIPLE MYELOMA CRITERIA:

Criteria for newly or recently diagnosed subjects

-Presence of clonal plasma cells in the bone marrow greater or equal to 10% or a
documented clonal plasmacytoma

AND

-Presence of an M-component; an M-component (IgG or IgA) in serum greater or equal to
1g/dl or in urine greater or equal to 200 mg/24 h.

ALTERNATIVELY, in absence of an M-component greater or equal to 1g/dl:

- an abnormal serum free light chain (FLC) ratio on the serum FLC assay or if the FLC
ratio is normal,

- baseline bone marrow must have 10% or greater clonal plasma cells.

AND, IN ADDITION:

- Presence, of one or more of the following attributable to the disease (in the
presence or absence of an M component):

- Calcium elevation greater than 11.5 mg/dl (2.65 mmol/l)

- Renal insufficiency: serum creatinine greater than 2 mg/dl (177 mmol/l)

- Hemoglobin less than 10g/dl (12.5 mmol/l) or 2 g/dl (1.25 mmol/l) below lower
normal

- Bone disease (lytic lesions or osteopenia)

- Other evidence of disease activity: repeated infections, secondary amyloidosis,
hyperviscosity, hypogammablobulinemia

- Must have high risk disease defined as the presence of any of the following:

- Stage II and III of the International Staging System defined as follows:

- stage I: - serum (Beta)2-microglobulin less than 3.5 mg/l plus

-----serum albumin greater or equal to 3.5 g/dl

- stage II: neither stage I nor III

- stage III: serum (Beta)2-microglobulin greater or equal to 5.5 mg/L

- del 13 or aneuploidy (by metaphase analysis33)

- del 17p13 by FISH or mutated p53

- (4;14) by FISH31

- (14;16) or t(14;20) by FISH

- plasmablastic morphology at diagnosis(35)

- circulating myeloma cells by FACS (CD38+/CD45low) post induction
therapy(36)

- High-risk disease as defined in a 70-gene ( MyPRS (TM)) or the 17-gene
condensed microarrays

OTHER ELIGIBILITY CRITERIA:

- Age greater than or equal to 18 years and less than or equal to 75 years. In subjects
between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly
evaluated before enrolling.

- Specifically, any history of cardio-vascular pathology or symptoms, not clearly
fitting the exclusion criteria will prompt an evaluation by a Clinical Center
Cardiologist and eligibility wil be considered on a case-by-case basis

- Must have received no more than 6 cycles of induction therapy for Multiple Myeloma.

- The planned High-Dose chemotherapy must consist of melphalan only and may be followed
by a post-ASCT consolidation.

- Karnofsky performance status of 70% or greater (ECOG 0 or 1). Lower KPS down to 50%
or ECOG of 2 may be acceptable if the restriction of activity is solely due to
intractable pain from myeloma lesions.

- Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal
limits. In case of low EF, the subject may remain eligible after a stress
echocardiogram is performed if the EF is more than 35% and if the increase in EF with
stress is estimated at 10% or more.

- Serum creatinine less than or equal to 2.5 mg/dl,

- AST and ALT less than or equal to 3 times the upper limit of normal,

- Bilirubin less than or equal to1.5 (except if due to Gilbert's disease).

- Corrected DLCO greater than or equal to 50% on Pulmonary Function Tests

- No history of abnormal bleeding tendency or predisposition to repeated infections.

- Patients must be able to give informed consent

DECISION TO ENROLL ON COHORT 5 B

The decision to enroll on cohort 5B or on cohort 6 will be made as follows:

- A subject will be enrolled on the cohort that has the smallest number of accrued
subjects of these two cohorts.

- In case of a tie, the subject will be enrolled on the cohort that did not enroll the
previous subject.

EXCLUSION CRITERIA:

- Prior allogeneic stem cell transplantation

- Hypertension not adequately controlled by 3 or less medications.

- History of cerebro-vascular accident within 6 months of enrollment..

- History of documented pulmonary embolus within 6 months of enrollment.

- Clinically significant cardiac pathology: myocardial infarction within 6 months prior
to enrollment, Class III or IV heart failure according to NYHY, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities.

- Patients with a history of coronary artery bypass grafting or angioplasty will
receive a cardiology evaluation and be considered on a case-by-case basis.

- HIV seropositive

- Patients known or found to be pregnant.

- Patients of childbearing age who are unwilling to practice contraception.

- Patients may be excluded at the discretion of the PI if it is deemed that allowing
participation would represent an unacceptable medical or psychiatric risk.