UARK 2008-02 A Trial for High-risk Myeloma Evaluating Accelerating and Sustaining Complete Remission

Inclusion Criteria: * Patients must have newly diagnosed active MM requiring treatment. Patients with previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. * Patients must be either untreated o have not had more than one cycle of systemic MM therapy, excluding bisphosphonates and localized radiation. * Patients must have high-risk disease, as defined by any one of the following: * GEP risk score of \> or = 0.66 or * LDH \> or = 360 U/L Rule out hemolysis, infection an contact PI for clarification * Zubrod \< or = 2, unless solely due to symptoms of MM-related bone disease. * Patients must have a platelet count of \> or = 50,000/uL, unless lower levels are explained by extensive bone marrow plasmacytosis. * Patients must be at least 18 years of age and not older than 75 years of age at the time of registration. * Participants must have preserved renal function as defined by a serum creatinine level of \< 3 mg/dL. * Participants must have an ejection fraction by ECHO or MUGA scan \> or = 45% * Patients must have adequate pulmonary function studies \> or = 50% of predicted on mechanical aspects (FEV squared, FVC, etc) and diffusion capacity (DLCO) \> or = 50% of predicted. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted if the principle investigator documents that the patient is a candidate for high dose therapy. * Patients must have signed an IRB-approved informed consent indicating their understanding of the proposed treatment and understanding that the protocol has been approved by the IRB. Exclusion Criteria: * Does not have high-risk disease * Poorly controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol. * Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years. * Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Subjects of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.