外周T治疗（西昌会议）.ppt

主要内容PTCL细胞淋巴瘤的分类PTCL的流行病学PTCL细胞淋巴瘤的预后因子PTCL细胞淋巴瘤的治疗PTCL细胞淋巴瘤新药物我们治疗PTCL经验门冬酰胺酶的作用机理32例PTCL患者L-Gemox方案不良反应血管免疫母T-细胞淋巴瘤常见几种T细胞淋巴瘤的治疗AITL的临床特征老年患者多见,男=女系统性淋巴结肿大结外受侵常见肝脾肿大,皮疹,骨髓骨髓受侵,浆膜腔渗出多样的体征和症状呈进行性进展B淋巴细胞的极度活跃多克隆高γ球蛋白白血症Coombs阳性溶血性贫血免疫低下和机遇性感染化疗易发生感染并发症AITL基因预测图谱Goodprognosis:B-cellassociatedgenesandgenesinhibitorytomyeloidfunctionPoorprognosis:ImmunosuppressivegenesincludingT-cellactivationinhibitorOSandEFSsignificantlybetterinlowriskpatientsdeterminedbyLOOCVLong-termsurvivorswithAITLdooccur;furtherstudyneededtoidentifythesepatientswhomaybecandidatesforalternatetherapyIqbalJ,etal.Blood.2010;115:1026-1036.AITLCell-cellcommunicationandadhesionCadherins,integrins,membranereceptors(CD10,CD40Letc)ImmuneresponseBcellandplasmacell–relatedgenesVascularbiologyVEGFrelatedChemokineandcytokinepathwayExtracellularmatrixLaminin,collagen,TGF-bPTCL-UProteinubiquinationRegulationoftranscriptionChemotaxisGenesoverexpresseddifferdeLevalL,etal.Blood.2007;109:4952-4963.AITLvsPTCL-U：基因表达谱GroggKL,etal.Blood.2005;106:1501-1502.GroggKL,etal.ModPathol.2006;19:1101-1107.

KanemitsuN,etal.Blood.2005;106:2613-2618.AITL起源于生发中心

(CXCL13表达)趋化因子是GC形成的关键AITL90%+vsPTCL-U10%淋巴组织炎增生没有CXCL13表达招募B细胞到淋巴结核淋巴滤泡肝脾窦内捕获B淋巴细胞活化B淋巴细胞促进DC细胞的增值分化复发/难治AITL的治疗选择临床试验(首选)联合化疗(多用于适合移植的患者)DHAP,ESHAP,剂量调整的EPOCH*,GDP,GemOx,ICE,MINE单药治疗(多用于不适合移植的患者)Alemtuzumab,bortezomib,cyclosporine,gemcitabine,romidepsin**在适合和不适合移植患者中均适用的方案NCCN.Clinicalpracticeguidelinesinoncology:non-Hodgkin’slymphomas.v.2.2013.DunleavyK,etal.LeukLymphoma.2007;48:449-451.DunleavyKetal.CurrOpinHematol.2007;14:348-353.血管免疫母细胞淋巴瘤靶向治疗免疫调节剂环孢素可以阻断T辅助细胞的活化美罗华可以消除活化的B细胞抗血管生成贝伐单抗可以靶向VEGF-A的高表达环孢素的有效率和毒性ResponsenDurationCR310+yrs,3.5+yrs*,1.5yrsPR518mos,9mos,9mos,2+mos*,1mos(BMT)ORR:66%(8/12);duration2-120m