Clinical, genomic and imaging predictor of myeloma progression from asymptomatic monoclonal gammopathies (Blood. 2014;123(1):78-85) CR 簡聖軒 VS 劉俊煌 教授 MGUS Asymptomatic MM Symptomatic MM Extra medullary Clonal cells PC > 10% End organ damage BM independent MGUS AMM Serum M-protein <3.0 g/dL + Marrow plasma cells <10% + No related organ damage No other B cell NHL or amyloidosis Serum M-protein ≥3.0 g/dL and / or Marrow plasma cells ≥10% (clonal) + No related organ or tissue impairment C R A B Observe ! PC > 10 %, M> 3g/dL PC > 10 %, M< 3g/dL PC < 10 %, M< 3g/dL N Engl J Med 2007;356:2582-90 51 gene Up regulation 19 gene down regulation EFS OS Prospective observation trail : SWOG S0120 MGUS, SMM, solitary plasmacytoma Hemogram, serum/urinary M protein, SEP, IEP, B2M, free light chain, metaphase karyotyping, MRI At 3,6 and 12 months at first year, then every 612 months Collected to isolate CD 138+ plasma cell with immunomagnetic bead selection Monitored by flow cytomerty for > 85% Affymetrix U133 plus 2.0 microarrays, generate risk score based on a validated 70-gene model (GEP-70) GEP -70score Univariate analysis Age ≧65 MRI focal lesion > 1 Hb <12 g/dL GEP-70 risk score > -0.26 Albumin< 4 g/dL B2M > 3 mg /L GEP-70 PI > -2.73 Serum M ≧3 g/dL Urine M > 0 g/dL GEP poly-PC > 11.6 Low level of uninvolved Ig A level of involved SFLC > 25 mg/dL Elevated ratio of involved/uninvolved SFLC > 10 Plasma > 20% in BM Addition of GEP improved cumulative R2 by approximately 11 % 11% Risk factor: SFLC >25 mg/dl M spike > 3g/dL GEP70 risk >-0.26 Risk factor: M spike > 3g/dL BM PC > 20 % Age ≧65 Risk factor: SFLC >25 mg/dl M spike > 3g/dL GEP70 risk >-0.26 Higher polytypic-PC risk score predicts reduced risk of progression Multivariate analysis VS Follow up time ? First prospective clinical trial Mode for risk identification Genomic and clinical based Monitor and intervention M 馬年行大運 M 馬到成功
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