Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

Inclusion Criteria: * Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for multiple myeloma; patients with AL amyloidosis and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) are excluded; measurable disease is not required * Patient undergoing autologous transplant as part of first line therapy * All races and ethnic groups are eligible for this study * Patients must also have an adequate autologous graft as defined as a cryopreserved peripheral blood stem cell (PBSC) graft containing \> 2 x 10\^6 CD34+ cells/kg patient weight * Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%) is required for eligibility; those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible * Absolute neutrophil count (ANC) \> 1000/uL * Platelet count \> 50,000 * Transfusion independent * Total bilirubin \< 1.5 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x the institutional upper limit of normal * Left ventricular ejection fraction \>= 40% * Carbon monoxide diffusing capability (DLCO) \> 50% predicted * Forced expiratory volume in 1 second (FEV1) \> 50% predicted * Forced vital capacity (FVC) \> 50% predicted * Ability to understand and willingness to sign a written informed consent document * Females of childbearing potential (FCBP) must not be pregnant as per institutional standard; if no institutional standard exists, then patients must have a negative serum or urine pregnancy test prior to transplant; a female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Exclusion Criteria: * Patients who are receiving any other anti-myeloma investigational agents * Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study; breastfeeding should be discontinued * Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to \< 1 year, or confound data interpretation * Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug