弥漫大B细胞淋巴瘤治疗进展.ppt

,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,概况,：缪,XX,，男性，,52,岁。,主诉,：活动后胸闷气急,8,月，加重,2,周。,现病史,：,8,月前，爬,4,层楼梯出现胸闷气急心悸，脸色苍白，休息后即可缓解。,1,月前因反复胸闷黑曚入住某院，期间出现三次胸闷气促、出汗乏力，意识模糊，无发作前驱症状。发病时,BP 65-70/34-40mmHg,，,HR 50/min,，考虑“血管迷走性晕厥”，予以起搏器植入。半月前因胸闷气促等症状再次就诊，心超示“大量心包积液，经穿刺，引出,800ml,淡红色混浊液体，胸水常规及生化：,WBC 1020/ul,，,RBC 2000/ul,，,ADA 66.2IU/L,；血总蛋白,37.1g/l,，,LDH 1534IU/L,。,自病以来，胃纳睡眠较差，体重减轻,9,公斤。,病例,T 37,度；,P 65,次,/,分；,R 17,次,/,分；,Bp 131/97 mmHg,神清，口唇无紫绀，全身浅表淋巴结未触及肿大，颈部增粗，颈静脉未见明显充盈，胸廓无畸形，心前区无膨隆，两肺呼吸音减低，心界左大，心律齐，收缩期可闻及粗糙心包摩擦音。腹平软，无压痛反跳痛，肝脾肋下未及，移动性浊音阴性。双手背部凹陷性水肿。双侧,Babinski,征阴性。,体检,胸部平片,胸部,CT,病理诊断,非霍奇金氏淋巴瘤（心包穿刺）,弥漫大,B,细胞淋巴瘤,IHC,：,LCA+,，,CD20+,，,CD3-,，,CD10-,，,bcl-6+,，,MUM1+,，,Ki67 90%+,临床诊断,非霍奇金淋巴瘤,弥漫大,B,细胞淋巴瘤,B,期，,aaIPI 3,分,（,non-GCB,，,non Germinal center B cell like,）,上腔静脉压迫综合症,起搏器植入术后,Ann Arbor staging classification for Hodgkins and NHL,治 疗,化疗及评估,Pre-Chemo,ESHAP,1st,09-4-15,29*23,ESHAP,2nd,09-5-7,Neuropenic Fibrile,17*18,12*7,ESHAP,3th,09-6-10,Cr 2.1mg/dl,，,Ccr 37.3ml/min,21*14,24*18,R-CHOP,25*20,30*22,Pre R-CHOP,Post R-CHOP,09-7-14,白细胞分化图,淋巴瘤细胞起源,非霍奇金淋巴瘤亚型分布,Non-Hodgkins Lymphoma,Classification Project,Blood 1997,WHO,分类一览表（,2008,）,DLBCL,的预后因素,利妥昔单抗使用后的,IPI,OS According to Gene-Expression Profiles,N Engl J Med,Vol.346,No.25.June 20,2002,Hans Decision Tree for DLBCL,a GCB case,a non-GCB cas,e,Hans CP.,et al.Blood.2004 Jan 1;103(1):275-82,DLBCL,高危因素,淋巴瘤治疗历史回顾,Hans et al.Blood 2004;103:275-282,CHOP,*,有效率尚可,*,结果易于复制,*,长期生存欠佳,*,需要改进,-MACOP-B,ACVBP,优于,CHOP,方案？,ACVBP vs CHOP-21,高危患者的自体干细胞移植,LNH87-2 PROTOCOL,侵袭性局灶,NHL,的治疗选择,Miller et al.,NEJM,1998;339:21-26,侵袭性局灶,NHL,的治疗选择（,SWOG8736,）,Miller TP,et al.,ASH,2002,大包块淋巴瘤的治疗选择,Bonnet et al,J Clin Oncol 26:787-792 2007,LNH 93-4:IPI=0,60 80 yr.,LNH 98.5,：利妥昔单抗（,Rituximab,）,Coiffier B,et al.N Engl J Med 2002;346:235.,LNH,98.5:,疗效分析,Coiffier B,et al.N Engl J Med 2002;346:235.,LNH-98.5,：,10,年,EFS/OS,分析,Coiffier B,et al.2009 ASH Poster,R-CHOP vs CHOP,，,10,年,OS,提高 了,5%,R-CHOP vs CHOP,，,CR,患者的,10,年,DFS,提高了,49%,MInT:,年轻患者的,R-CHOP,疗效,Michael Pfreuddschuh at al.oncology.Vol7 May 2006,预后良好的弥漫大,B,细胞淋巴瘤年轻患者,经美罗华联合,CHOP,样方案或单独,CHOP,样方案治疗后的比较研究（,MInT,）,化疗疗效对,FFS/OS,的影响,Cunningham et al.J Clin Oncol 2009;27(suppl):435s(abstract 8506).,如何改进,aaIPI23 DLBCL,年轻患者的生存,?,in the rituximab era,aaIPI 23,患者的自体干细胞移植研究,Goals:,increase the CR rate,decrease the relapse rate,R-ACVBP/ASCT,vs ACVBP-r/ASCT,R-ACVBP/ASCT,改善了,IPI2-3,患者的生存期,R-ACVBP,诱导缓解后,ASCT,方案,优于,ACVBP/ASCT,或美罗华维持方案,Gisselbrecht C,et al.ASH 2008,R-ACVBP,诱导缓解后,ASCT,方案,ACVBP/ASCT,或美罗华维持方案,LNH03-3B,：,IPI,分层分析,Gisselbrecht C,et al.ASH 2008.,R-CHOP21,被推荐为治疗,DLBCL,标准方案,新靶点的发现,BCL-6,在,DLBCL,亚型中的表达,DA-EPOCH,疗效分析,NF-,B target genes expression in DLBCL,Davis et al.J Exp Med 2001,42,42,ABC,细胞株的生长和存活依赖,NF-kB,通路,IKK Inhibition(,m,M),Cell Number(%of control),0,25,50,75,100,0,1.6,3.1,6.3,12.5,25,50,ABC DLBCL,OCI-Ly3,OCI-Ly10,GCB DLBCL,OCI-Ly7,OCI-LY19,SUDHL-6,-NF-,B,和,IKK,激酶 是,ABC DLBCL,的活性成分；,但不是,GCB DLBCL,细胞株的活性成分,-,抑制,NF-,B,途径导致,ABC,生长的抑制,，,Dunleavy and Wilson,Bortezomib/EPOCH Phase II Trail,Ibrutinib:A first in class inhibitor of BTK,Ibrutinib,疗效分析,Hans,分型的意义,Lenz et al.,NEJM 359:2313-23(2008),R-CHOP between ABC and GCB,Lenalidomide,治疗淋巴瘤,Wiernik P et al.et al.Blood 2006;108:160a(abstract 531),Lenalidomide in R/R in Non-GCB like,Cancer November 15,2011,Forty patients with relapsed/refractory,DLBCL were included,CD5-positive diffuse large B-cell lymphoma,BLOOD,1 FEBRUARY 2002 VOLUME 99,NUMBER 3,Annals of Oncology 22:16011607,2011,CNS relapse in CD5-positive DLBCL patients.,Annals of Oncology 22:16011607,2011,PET,在个体化治疗中的价值探讨,两疗程后,PET,评估或有助于患者的个体,化分层治疗，预后不良患者通常,PET+,。,Haioun C,et al.Blood 2005.,Botezomib-based regimen biweekly 09-8-31(8-4),17*14,2 cycles of chemo with Botezomib-based regimen weekly,含,Bortezomib,方案化疗后,2 months after 3th cycle of chemo with Botezomib-based regimen,含,Bortezomib,方案化疗后,DLBCL,的明天,T,HANKS,