诊断与鉴别诊断与分层

Click to edit Master title style,Click to edit Master text styles,second level,third level,fourth level,Click to edit Master title style,Click to edit Master text styles,second level,third level,fourth level,多发性骨髓瘤诊断、鉴别诊断与分层,MM,诊断标准,(WHO Criteria Before 2008):1M+1m or 3m,主要诊断标准,活检发现有浆细胞瘤,骨穿分类浆细胞,30%,血清,M,蛋白,IgG35g/L,或,IgA20g/L,或,24h,尿单克隆轻链,1g/L,次要诊断标准,骨穿分类浆细胞,10%30%,M,蛋白量低于主要标准,溶骨性损害,正常,IgG6g/L,IgA1g/L,IgM0.5g/L,诊断,MM,应注意的问题,具体数值的界定是人为的，且骨髓瘤细胞分布常常是不均匀的,把握瘤细胞的生物学特性和疾病本质,生物学上，骨髓瘤细胞表现为单克隆性,临床上，,MM,具有危害性，造成器官损害,-(CRAB),特征,重视形态学在,MM,诊断中的重要性,注意与相关疾病的鉴别，尤其采用,3,条次要标准时更应谨慎,MM,诊断标准,(WHO Criteria After 2008):,克隆性浆细胞增生造成器官与组织损伤,高血钙,(hyper,c,alcemia),肾功能不全,(,r,enal insufficiency),贫血,(,a,nemia),骨质破坏,(,b,one lesions),其他：感染、淀粉样病变等,CRAB,浆细胞克隆性的鉴定,蛋白水平,:,膜电泳、免疫电泳、免疫固定电泳、,sFLC,及其比值的改变,细胞水平,:,轻链同种型限制性,(,免疫组化或免疫荧光,),基因水平：,IgH,、,、,基因的克隆性重排,Kyle RA and Rajkumar SV.Cecil Textbook of Medicine,22nd Edition,2004,Immunofixation to Determine Type of Monoclonal Protein,IgG kappa,M protein,在细胞水平上，运用,FACS,检测外周血和骨髓中,和,阳性细胞,监测,LCIS,现象,kappa,lambda,kappa,Immunophenotyping,骨髓瘤细胞,克隆性：轻链同种型限制性,(kappa/lambda),分化紊乱：,CD 138+,以及,CD 38+/CD45-,克隆性浆细胞,CD19-/CD56+,，正常浆细胞,CD19+/CD56-,，大约,15-20%MM,患者浆细胞表达,CD20,抗原,San Miguel,Baillieres,Clinical Haematol,1995;4:735-59,CD38+/CD45-Clonal Lambda PCs on Flow,Dual Fluorescent Analysis,on Myeloma Plasma,鉴别诊断,反应性浆细胞增多（,RP,）,骨转移性癌、骨结核的溶骨性病变,其他可以出现,M,蛋白的疾病,其他可以出现,M,蛋白的疾病,WM,MGUS,淀粉样变性,孤立性浆细胞瘤（骨或髓外）,非霍奇金淋巴瘤（,B,细胞性）,Castleman,病,CLL,POEMS,重链病,浆细胞白血病,MM,与骨转移性癌、骨结核的溶骨性病变,病例,1,女性，,56,岁，胸痛,8,年，贫血，,Hb 56g/L78g/L,BM,浆细胞,4%9%,。,M,蛋白鉴定,IgG,单克隆，,IgG 26g/L31g/L,。多处肋骨破坏，大量胸水，但从未找到癌细胞。在外院诊断,MM,，经过,8,次化疗症状无改善。,入我科后体检发现左乳皮肤呈桔皮样改变，活检证实为乳腺癌,MM,与骨转移性癌、骨结核的溶骨性病变,病例,2,男性，,82,岁，体检时发现球蛋白升高。,M,蛋白鉴定,IgM,单克隆，,IgM 12g/L20g/L,。,BM,浆细胞,6%8%,。,X,线摄片示头颅有,3,处直径约,1cm,的缺损。血常规正常。,追问病史，患者,3,年前曾因硬脑膜下血肿行钻孔减压术。,IgM-MM,与巨球蛋白血症的鉴别,溶骨改变,高黏滞综合征,淋巴样浆细胞,肝脾肿大,CD20,表达,游离轻链及其比值,ISS,：,2 M+,血清白蛋白,I,期,:,2,M 60%:38 pts,p=5.10,-11,No del(17p):494 pts,Del(17p)60%:38 pts,p=4.10,-12,Cytogenetic correlations,t(4;14)and del(13),84%,del(13)=0 or 0,p=2.10,-13,(C,),del(13),75%,p=2.10,-11,(,C,),Tight association,del(17p)and del(13),77%,del(13)=0 or 0,p=6.10,-5,(C,),del(13),75%,p=4.10,-4,(,C,),Tight association,del(17p)and t(4;14),14%,p=0.51,Independent parameters,Del(13)et t(4;14)/del(17p),p=0.41,p=0.12,Del(13)0,no t(4;14),no del(17p),EFS,OS,Multiparametric analysis,Independent prognostic parameters,EFS:,del(17p),t(4;14),b,2m3 ou 4,Hb3 ou 4,Prognostic parameters:,del(13),t(4;14),del(17p),1q gains,b,2m3/4,Hb10,albumine30 or 35,platelets,3%,High-Risk,20%,Intermediate-Risk,20%,Standard-Risk,60%,*,*Prognosis is worse when associated with high beta 2 M and anemia,*LDH ULN and beta 2 M 5.5 in standard risk may indicate worse prognosis,*t(11;14)is associated with plasma cell leukemia,mSMART,2.0:,Classification of Active MM,FISH,Del 17p,t(14;16),t(14;20),GEP,High risk,signature,All others including:,Hyperdiploid,t(11;14),t(6;14),FISH,t(4;14)*,Cytogenetic Deletion 13 or hypodiploidy,PCLI,3%,3 years,5 years,7-10 years,mSMART,2.0:,Treatment of Active MM,Novel approaches,New drugs,“TT3 like”approach for p53 deletion?,Regimen which provides a high ORR and which minimizes early toxicity,HDM could be delayed in patients achieving CR,Lenalidomide maintenance,Bortezomib based,combination,HDM+/-consolidation,Lenalidomide,maintenance,Targeted therapy,High-Risk,Intermediate-Risk,Standard-Risk,GEP,分层对,TT3,预后的影响,TT4,方案：更强调分层治疗和强化治疗,低危组,高危组,TT3,组,TT3-LITE,组,同前,诱导,:VDT-PACE1,巩固,:VDT-PACE1,维持：,VRD,1,疗程剂量递增,VDT-PACE,采集,PBSC,(,加大强度和密度的,VDT-PACE+PBSC),4,M-VRD,4,(mel 10mg d1-4,+VRD),PBSC,VRD/,月,3,年,MEL,100 mg/m2 d1,4,7,+VRD+ASCT d8,VRD,MEL,100 mg/m2 d1,4,7,+VRD+ASCT d8,分层主要根据,GEP,Best Pract Res Clin Haematol.2007 Dec;20(4):761-81,nCR,nCR,总结,MM,诊断应把握瘤细胞生物学特性和疾病本质,分层治疗是当今,MM,治疗的趋势所在，最佳分层方案尚未确定,ISS,分期系统,游离轻链,细胞遗传学,分子生物学,基因表达谱、蛋白组学,