多发性骨髓瘤的精确诊断课件

,Click to edit Master title style,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,杜鹃,上海长征医院血液科,全军骨髓瘤与淋巴瘤疾病中心,多发性骨髓瘤的精确诊断,1,2,MGUS SMM MM,10%BMPC AND,10%BMPC,OR,3gm/dL M protein AND,No CRAB,Clonal PCPD,CRAB,CRAB,:C=Calcium(elevated),R=Renal failure,A=Anemia,B=Bone lesions,Rajkumar SV.Cell Textbook of Medicine,24,th,Edition 2012,3,MGUS SMM MM,10%BMPC AND,10%-60%BMPC,OR,3gm/dL S.M protein OR,500mg/24h Ur.M protein AND,No MDE,PCPD,1 or more MDE,CRAB,60%BMPC,100 FLC ratio,1 MRI focal lesions,2014,年修改的,IMWG,诊断标准,Rajkumar V et al Lancet Oncol 2014,15:e538-48,MDE,myeloma defining events,60%BMPC,鉴定其克隆性，骨髓活检、涂片、流式,中国多发性骨髓瘤诊治指南,(2015,版,),4,SMM VS MGUS,进展比例,5,Perez-Persona E,et al.Blood.2007;110:2586-92.,95%aPC/BMPC or paresis,n=22(10 progr.),95%aPC/BMPC+paresis,n=39(28 progr.),No adverse factors,n=28(1 progr.),120,96,72,48,24,0,1.0,0.8,0.6,0.4,0.2,0.0,Months,TTP(%),Median not reached,Median,73 months,p=0.003,Median 23 months,8%,42%,82%,High Risk,Low Risk,冒烟型骨髓瘤向症状性骨髓瘤演变风险,based on the%of aberrant PCs by immunophenotype plus immunoparesis,1.0,5 yrs,6,MM,的诊断标准,(IMWG),的更新的缘由,不必治疗,!,“,冒烟型,”,骨髓瘤,(,MC 3 g/dl&/or PC 10%.No CRAB),Early MP vs.deferred MP,1,2,3,.,No benefit,Thalidomide,4,5,only 30%PR&No benefit in TTP/OS,Bisphosphonates,6,7,.No benefit in OR/TTP/OS,1.Hjorth M,et al.Eur J Haematol.1993;50:95-102.,2.Grignani G,et al.Br J Cancer.1996;73:1101-07.,3.Riccardi A,et al.Br J Cancer.2000;82,4.Rajkumar SV,et al.,Am J Hematol 2010;,85(10):737-40,5.,Barlogie B,et al.Blood.2008;112:3122-25.,6.,Musto P,et al.,Leuk Lymphoma.2011;52(5):771-775,7.Musto P,et al.Cancer.2008;113:1588-95.,7,Lenalidomide+dex,（,Rd),对高危,冒烟型,MM,患者的临床试验研究,median TTP,21,(P0.001),median TTP,not reached,13 Progressions(22%),47 Progressions(76%),Mateos et al NEJM 2013,ASH 2014(Abs3465),To meet,SMM diagnosis criteria,at least,95%phenotypically aberrant,plasma cells in the BMPC,reductions,in one or two uninvolved,immunoglobulins of,more,than 25%,9 cycle Rd induction therapy followed,by maintenance therapy with lenalidomide,8,Lenalidomide+dex,（,Rd),对高危,冒烟型,MM,患者的临床试验研究,TTP,OS,TTP,Mateos et al NEJM 2013,ASH 2014(Abs3465),OS from the date of,inclusion in the study,OS from the date of,diagnosis of SMM,94%,80%,94%,78%,3 years,5 years,This randomized,phase 3 trial showed that,early treatment with Rd,followed by maintenance therapy with lenalidomide,in patients with,high-risk SMM,significantly delayed the time to progression,to symptomatic disease and,resulted in an OS benefit.,9,Progression to myeloma occurred,within 2 years,of the,diagnosis in 95%,of the patients with,60%or more,bone marrow,plasma cells,with a median time to progression of,7 months,(95%CI,1.0 to 12.9),1,.,Time to progression of disease patients with SMM,Rajkumar SV,et al.N Engl J Med.2011,Kastritis E.et al.Leukemia 2013,Waxman AJ.et al.J Clin Oncol 2014,95%,N=655 SMM(1996.01-2010.06 at Mayo Clinic),N=21 pts(3.2%),Greek Myeloma Group,2,the University of,Pennsylvania,3.,10,TTP of disease patients with SMM,Mayo 2007,In 2007,N Engl J Med,During past 26 years,276 SMM,at Mayo Clinic,6 of 276 patients(2%),60%PC in BM,4,patients progressed to symptomatic MM from,3 to 9 months,1,of these patients died,13.5,months(no specific reason),1,SMM progressed to MM,50,months,death within 2 years of that date.,Kyle RA,et al.N Engl J Med.2007 Jun 21;356(25):2582-90,.,11,完整的单克隆免疫球蛋白,单克隆游离轻链,血清蛋白电泳,血清免疫固定电泳,尿免疫固定电泳,血清游离轻链,类,IgG,IgA,IgD,IgM,IgE,型,、,血清游离轻链（,sFLC,）,12,IgG,IgA,IgM,FLC,Total light chain assay versus,sFLC,assay,Total,assay,Serum FLC,assay,FLC,8g/L,2g/L,1g/L,10mg/L,10mg/L,In healthy individual:,Total,=11.01 g/L,In healthy individual:,Free,=10 mg/L,In,light chain myeloma,Total,=11.05 g/L,50mg/L,In,light chain myeloma:,Free,=50 mg/L,50mg/L,8g/L,2g/L,1g/L,g/L polyclonal immunoglobulin,background,13,，,mg/L,，,mg/L,SPEP,1,2,000,500,Serum IFE,1,150,100,UPEP,2,30,30,Urine IFE,2,20,20,sFLC assay,3,1.2,1.7,1.Katzmann et al.Clin Chem.2002;1437-1444.,2.Beetham et al.Ann Clin Biochem.2000,37:581-587.,3.Bradwell et al.Serum Free Light Chains Analysis.4,th,ed.,“,高度敏感,”,的,“,定量,”,检测,14,“,早期,”“,及时,”,的检测,IgG,20-25 days,IgA,6-7 days,IgM,6-8 days,Free Kappa,2-4h,Free Lambda,3-6h,15,Dispenzieri A.et al.Blood 2008,sFLC ratio 8 or 0.125,8sFLC ratio 0.125,40%,(2years),TTP to symptomatic MM from,sFLC,ratio,16,sFLC ratio as a biomarker for high-risk SMM,Median TTP was 15 mo,sFLC ratio 100,Median TTP was 55 mo,sFLC ratio 100,72%,28%,Larsen JT,et al.Leukemia.2013,586 patients with SMM,diagnosed between 1970 to 2010,Variables,sFLC 1 focal lesion on spinal MRI in 9 of 65 patients(,14%,)with SMM.,高危,SMM,的,MRI,1,处骨质破坏,21,MRI value in patients with SMM,Regarding,smoldering or asymptomatic myeloma,all patients should undergo whole-body MRI(WB-MRI;or spine and pelvic MRI if WB-MRI is not available),and,if they,have one focal lesion of,a diameter 5 mm,they should be considered to,have symptomatic disease,that,requires therapy,.,22,PET/CT focal,but not osteolytic,lesions predict the progression of SMM to active