Serum metabolomic profiling correlated with ISS and clinical outcome for multiple myeloma patients treated with high-dose melphalan and autologous stem cell transplantation.

The metabolome, which is the final down-stream global product of metabolic processes in organisms, is not sufficiently described in multiple myeloma (MM) patients. The aim of this study was, therefore, to study the serum metabolomic profile using proton nuclear magnetic resonance (H-NMR) spectroscopy, and its relationship to clinical characteristics and patient outcome. Serum samples, which were taken at diagnosis, from 201 MM patients who underwent high-dose melphalan followed by autologous stem cell transplantation as the first-line therapy, were analyzed. We found that the metabolomic profile differed between patients with different MM International Staging System (ISS) stages. The profile revealed increased levels of cholesterol, phospholipids, high-density lipoprotein, low-density lipoprotein, apolipoproteins A1 and A2, valine, and leucine in ISS I patients compared with ISS III patients. The metabolomic profile also differed between patients with IgA and IgG paraproteins, predominantly because of higher levels of high- and low-density lipoprotein subfractions in IgA patients. The exact pathway of metabolism leading to accumulation of these metabolites is still elusive, but this study indicates an area of interest for further investigation in the search for new therapy targets and prognostic markers for this disease.