Prognostic value of high serum lactate dehydrogenase in plasma cell dyscrasias: a re-evaluation in the context of cytogenetic aberration data

Th e clinical course of multiple myeloma (MM) is highly heterogeneous. Genetic alterations largely contribute to the clinical heterogeneity observed in MM. Although cytogenetic aberration has been used as a prognostic factor, genetics alone cannot fully explain tumor heterogeneity. Moreover, some patients in the low-average genetic risk group have a poorer prognosis [1]. Lactate dehydrogenase (LDH) is a key enzyme in glycolysis that converts pyruvate to lactate, which is an energy source for tumor cells. Th e impact of high serum LDH on the survival of patients with MM is still controversial. Several studies have indicated that high LDH is associated with features of advanced disease and shorter survival in patients with symptomatic MM [2,3], but most of these studies did not really include the role of genetics, and whether LDH can maintain its signifi cance in the presence of geneticbased testing remains undefi ned. Moreover, the incidence of increased LDH level and its impact on the survival of patients with refractory/relapsed multiple myeloma (RRMM) are rarely reported. To address these issues, an analysis was performed in a patient cohort with plasma cell disorders for whom pretreatment LDH and complete fl uorescence in situ hybridization (FISH) data were available. Th ree hundred and ten patients with plasma cell dyscrasias were enrolled in this study between January 2004 and December 2012, with 238 cases being newly diagnosed multiple myeloma (NDMM) and 72 cases being RRMM with a median follow-up of 3 years from diagnosis. Patients were diagnosed as having MM according to the International Myeloma Working Group (IMWG) criteria [4]. Serum LDH levels were determined before initiation of primary treatment or salvage chemotherapy in all patients. High LDH was defi ned as serum LDH above the institutional upper limit of normal (220 U/L). Newly diagnosed patients were divided into two groups based on their chemotherapy: 96 patients with symptomatic MM were treated with thalidomide-based chemotherapy, and 142 patients with myeloma received bortezomib-based therapy. All MM samples were purifi ed using Miltenyi technology (anti-CD138-coated magnetic beads; Paris, France) before FISH, as previously reported [5]. Plasma cells were then analyzed using DNA probes specifi c for the following chromosomal aberrations: del(13q14), del(17p), 1q21 amplifi cation, t(11;14), t(4;14) and t(14;16). A total of 200 interphase nuclei were analyzed. Cut-off values recommended by the European Myeloma Network (EMN) were used [6].