Abstract
There is significant heterogeneity among multiple myeloma (MM) patients with the survival duration varying greatly from a few months to several years. This study retrospectively analyzed serum lactate dehydrogenase (LDH) in 105 cases of newly diagnosed elderly MM patients to investigate its value for outcome prediction. Serum LDH concentrations were evaluated prior to induction therapy. Prognostic analyses were carried out based on LDH levels and patients’ other clinical data. We also applied the recently proposed Revised International Staging System (R-ISS) to 70 patients with the available data. Of all the patients, elevated serum LDH levels (≥271U/L) were observed in 13.3% (14 out of 105) patients at diagnosis. Compared with normal LDH group, high LDH group had significantly shorter overall survival (OS) (15.5 vs. 52.5 months, p = 0.002) and median progression free survival (PFS) (12.0 vs. 24 months, p = 0.030), as well as 2-year OS rate (20% vs. 81%, p < 0.001) and PFS rate (22% vs. 44%, p = 0.005). A multivariate analysis identified high LDH as a unique independent adverse prognostic parameter for both OS and PFS. In addition, there were significant differences between R-ISS II and R-ISS III patients in both median OS (52.5 vs. 15.5 months, p < 0.001) and PFS (23 vs. 7.5 months, p = 0.004). Furthermore, high LDH was a unique independent adverse indicator for overall response rate (ORR) and early death in elderly MM patients. These results identified LDH as an unfavorable prediction for the outcome of Chinese elderly patients with MM. R-ISS based on LDH is superior to ISS in prognostic assessment.
Highlights
Multiple myeloma (MM) is a hematological malignancy characterized by malignant proliferation of abnormally cloned plasma cells that produces monoclonal immunoglobulin, resulting in clinical symptoms including infection, anemia, kidney damage and bone lesion [1]
Medial progression free survival (PFS) was 24.0 months in normal lactate dehydrogenase (LDH) group, while 12.0 months in high LDH group (p = 0.030) (Figure 1)
It has been reported that increased LDH is correlated with malignant degree and inferior prognosis
Summary
Multiple myeloma (MM) is a hematological malignancy characterized by malignant proliferation of abnormally cloned plasma cells that produces monoclonal immunoglobulin, resulting in clinical symptoms including infection, anemia, kidney damage and bone lesion [1]. The production of glucose metabolites is 5~10 times in tumor cells than that in normal tissues, most of which is converted to lactate that increase the release of enzyme to human blood [3]. Among these enzymes, serum lactate dehydrogenase (LDH) is widespreadly distributed in human tissue. Cancer cells rely on increased glycolysis resulting in increased lactate production in addition to aerobic respiration in the mitochondria, even under oxygen-sufficient conditions. It has been identified as a sensitive index for hypoxia, anaerobic glycolysis, malignant transformation in cellular metabolism [4]. It has been reported that elevated LDH www.impactjournals.com/oncotarget is correlated with increased disease aggressiveness, high proliferation rate, and the presence of tumor mass [5,6,7]
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