ALBERT

Description: OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia. Most patients had shrinking buccal pad fat and weight loss at disease onset, indicating abnormal lipid metabolism. Manifestations of POEMS syndrome, such as the elevated serum level of vascular endothelial growth factor, may also be mediated by lipids. However, the characteristics of serum lipidome of patients with POEMS syndrome have not been described. Therefore, this study aims to describe serum lipidome characteristics in patients with POEMS syndrome. METHODS: Serum samples of 24 POEMS syndrome patients newly-diagnosed at Peking Union Medical College from September, 2017 to July, 2018 were collected at baseline and after at least one cycle of treatment. Serum was also collected from a group of 24 healthy participants who were age-, gender-, BMI-matched with patients. UPLC-ESI-QTOF/MS profiling was used to analyze the molecular profile of lipid-containing organic extract of serum samples in the 320-1000 Da range. Multivariate data analysis (PCA and PLS-DA) was used to identify altered lipids between matched serum samples. For altered lipids between patients and healthy controls, lipid related genes were identified with the human metabolome database. Lipid related genes overlapped with genes in transcription files specific to POEMS syndrome compared with normal plasma cells, MGUS and MM reported in a Japanese series were identified. RESULTS : POEMS syndrome patients had serum lipidome distinct from normal people, which is characterized by a decrease in most altered fatty acyls (82.6%, 43/52) and glycerolipids (81.8%, 18/22). (Figure A) The baseline serum 17-oxo-20Z-hexacosenoic acid level was independently associated with disease(OR 1.07, 95% CI 1.01-1.13, p = 0.021). A two-fatty-acyl lipid model could be constructed by leave-one-out cross validation based on peak intensity of 17-oxo-20Z-hexacosenoic acid andΩ-3 arachidonic acid to identify patients and healthy control with an accuracy of 100%. (Figure B) Comparing serum lipids pre- and post-treatment, 100% (14/14) altered fatty acyls and glycerolipids (3/3) increased after treatment, of which 50% fatty acyls and all glycerolipids overlapped with baseline decreased lipids compared with healthy control. (Figure C) In patients with complete or partial VEGF remission after treatment, sphingolipids AS 1-1, Cer(d18:1/17:0) and glycerophospholipid lysoPE(0:0/18:2(9Z,12Z)) was lower than in patient with poor VEGF remission. (Figure D) Of all 358 genes related with altered lipids between patients and healthy control, 6 genes were reported to be upregulated in CD138+ cells in the bone marrow of POEMS syndrome than in MGUS and 8 genes than in MM. MGLL, a gene with function of converting monoacylglycerides to free fatty acids and glycerol, was expressed higher in POEMS syndrome than in both MGUS and MM and may be related with decreased serum glycerolipids. PLA2G2D, a gene encodes a secreted member of the phospholipase A2 family, was expressed higher in POEMS syndrome than in MGUS and may be responsible for decreased lysolipids after treatment. CONCLUSION: POEMS syndrome patients had a distinct serum lipidome characteristic from healthy control. A two-lipids model could distinguish patients and healthy people with high accuracy. Altered lipids and lipids related genes indicate POEMS syndrome specific alteration in glycerolipids and lysolipids metabolism compared with MGUS and MM, providing a potential insight for further study of molecular mechanism of POEMS syndrome. Figure Disclosures No relevant conflicts of interest to declare.

Description: OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort. METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (

Description: Background: POEMS syndrome is a rare plasma cell dyscrasia. Despite the presence of monoclonal protein, POEMS syndrome patients commonly have less than 5% monoclonal plasma cells in the bone marrow. Only one study has reported the genetic and transcriptional features of bone marrow plasma cells, and the underlying role of aberrant plasma cells is not well understood. Herein, in the current study, we aimed to characterize the genetic profile of bone marrow CD138-positive cells from Chinese patients with newly diagnosed POEMS syndrome. Methods: Forty-two patients with newly diagnosed POEMS syndrome based on the International Myeloma Working Group criteria at our institute were included in our study. Twenty milliliters of bone marrow aspirates was obtained and sorted by magnetic microbeads conjugated to monoclonal human anti-CD138 antibodies. The mutational features of these bone marrow plasma cells were analyzed using a two-step strategy. DNA of the bone marrow plasma cells from ten patients was first sequenced by whole exome sequencing to find significantly mutated genes and mutated driver genes, with paired peripheral blood mononuclear cells as a control. Bone marrow plasma cells of an additional thirty-two patients were then analyzed by target region sequencing to validate the mutations. Results: Whole exome sequencing of 10 newly diagnosed patients showed a total of 170 somatic mutations in exonic regions and splicing sites. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, CUX1) were identified in five patients. The mutation spectrum of WES revealed C 〉 T/G 〉 A as the most common mutation type, while the mutation signature was not the same as known signatures reported in various cancer types. For significant pathway and gene ontology analysis, 69 genes with possibly pathogenic nonsynonymous mutations were selected. Mutated genes were enriched in pathways including "chromatin organization", "chromatin modifying enzymes", and "apoptosis", and terms such as "cellular anatomical entity", "regulatory region nucleic acid binding" and "centrosome" that are used to describe cellular structure construction. To evaluate the mutation prevalence of genes identified in WES, we performed target region sequencing of 77 candidate genes in 32 other patients. The candidate gene list consisted of significantly mutated genes and known driver genes identified in WES, recurrently mutated genes previously detected in POEMS syndrome, the VEGF gene, and genes of light-chain amyloidosis, multiple myeloma, hematopoietic disease or lymphoid neoplasm in the public databases. As a result, a total of 32 mutated genes were identified in 28 of 32 patients. Genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Conclusions: Heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome were revealed in our study. The mutational landscape of POEMS syndrome might share some similarity to that of other plasma cell diseases. Disclosures No relevant conflicts of interest to declare.