NKT细胞淋巴瘤周剑峰

NK细胞增殖性疾病同济医院血液内科周剑峰2015年06月07日T和NK细胞肿瘤的分类：WHO2008WHO2008:thematureT-cellandNK-cellneoplasmsT-cellprolymphocyticleukemiaT-celllargegranularlymphocyticleukemiaChroniclymphoproliferativedisorderofNK-cells*AggressiveNKcellleukemiaSystemicEBV+T-celllymphoproliferativediseaseofchildhood(associatedwithCAEBV)Hydroavacciniforme-likelymphomaAdultT-cellleukemia/lymphomaExtranodalNK/Tcelllymphoma,nasaltypeEnteropathy-associatedT-celllymphomaHepatosplenicT-celllymphomaSubcutaneouspanniculitis-likeT-celllymphomaMycosisfungoidesSézarysyndromePrimarycutaneousCD30+T-celllymphoproliferativedisorderLymphomatoidpapulosisPrimarycutaneousanaplasticlarge-celllymphomaPrimarycutaneousaggressiveepidermotropicCD8+cytotoxicT-celllymphoma*Primarycutaneousgamma-deltaT-celllymphomaPrimarycutaneoussmall/mediumCD4+T-celllymphoma*PeripheralT-celllymphoma,nototherwisespecifiedAngioimmunoblasticT-celllymphomaAnaplasticlargecelllymphoma(ALCL),ALK+Anaplasticlargecelllymphoma(ALCL),ALK−*2001WHO2008WHOCommentsAngioimmunoblasticLymphomaAngioimmunoblasticLymphomaDefinitionoforigincellAnaplasticLargeCellLymphoma2variantsbasedonALK(+/-)expressionPrognosticimportanceUnspecifiedPeripheralT-cellLymphomaPeripheralT-cellLymphomasnotOtherwiseSpecified3variants:lymphoepitelioidlymphoma,Tzonelymphoma(2001WHO)andfollicularlymphoma(2008WHO)T/NK-celllymphoma,nasaltypeT/NK-celllymphoma,nasaltypeNochangesEntheropathy-associatedT-celllymphomaEntheropathy-associatedT-celllymphomasTwovariants:classicalandmonomorphictypeswithgeneticchangescommontobothHepatosplenicT-celllymphomaHepatosplenicT-celllymphomaNochangesSubcutaneouspanniculitis-likeT-celllymphomaSubcutaneouspanniculitis-likeT-celllymphomaOnlyabandassociatedwithautoimmunedisorderMycosisfungoidesMycosisfungoidesNewstagingandnewinformationaboutpathogenesisSézarysyndromeSézarysyndromeNewmarkersPrimarycutaneousanaplasticlargecelllymphomaPrimarycutaneousanaplasticlargecelllymphomaRecognitionofCD8+casesLymphomatoidpapulosisLymphomatoidpapulosisThreehistologicaltypesPrimarycutaneousgamma-deltaT-celllymphomaThreehistopathologicpatterns:epidermotropic,dermic,andsubcutaneoussubtypesPrimarycutaneousCD8+aggressiveepidermotropiccytotoxicT-celllymphomaProvisionalentityPrimarycutaneousCD4+small/mediumT-celllymphomaProvisionalentityBlasticNK-celllymphomaPlasmocytoiddendriticcellneoplasmNowitisoneofthemyeloidneoplasmsT-cellprolymphocyticleukemiaT-cellprolymphocyticleukemiaNochangesT-celllargegranularlymphocyticleukemiaT-celllargegranularlymphocyticleukemiaNewetiologicalfeaturesandnewmarkersChroniclymphoproliferativedisorderofNK-cellsProvisionalentityAggressiveNK-cellleukemiaAggressiveNK-cellleukemiaNochangesAdultT-cellleukemia/lymphomaAdultT-cellleukemia/lymphomaDefinitionoftheregulatoryT-cellnormalcounterpartT和NK细胞肿瘤分类的主要变化EBV相关淋巴增殖性疾病JKoreanMedSci.2008Apr;23(2):185-92.EBV相关T/NK细胞增殖性疾病JDermatol.2014;41(1):29-39.潜伏性感染，不是裂解式感染，抗病毒治疗无效NK/T细胞淋巴瘤NK/T细胞淋巴瘤亚型分布NK/T细胞淋巴瘤占到所有PTCL的10.4%JClinOncol,2008,26(25):4124-30NK/T细胞淋巴瘤特征分为鼻型(68%)和非鼻型(26%),其他为侵袭型（6%）病理表现：形态多样，表现为血管中心性、大量坏死和血管浸润表型：大部分为NK细胞（EBV+，CD56+）鼻型与非鼻型NK/T细胞淋巴瘤鼻型非鼻型侵犯部位上呼吸皮肤、睾丸、胃肠道疾病晚期27%68%肿块5cm12%68%超过2个鼻外病灶16%55%LDH升高45%60%B症状39%54%5年OS率42%9%中位OS19月4月鼻型与非鼻型NK/T细胞淋巴瘤Nasaltype:41%Non-nasal:22%Nasaltype:34%Non-nasal:13%AnnOncol2008;19:1477-1484放疗在NK/T细胞淋巴瘤中的地位仅早期患者可作为根治手段，其余多数与化疗联用什么样的NK/T细胞淋巴瘤可以单纯放疗？Nasalversusextra-nasalthestageofthediseaseStageIdiseasearefurtherstratifiedbasedonriskfactorsAge≥60years,Bsymptoms,ECOGperformancestatus≥2RegionallymphnodeinvolvementLocaltumorinvasionElevatedLDHHighKi-67stainingEBVDNA≥6.1x107copies/mL更新了治疗方案后，化疗是必不可少的治疗手段局限期鼻型NK/T细胞淋巴瘤单纯放疗RR和CR分别达78-94%和66-94%，但5y-OS和中位OS仅分别为35%-83%和50%患者出现皮肤、骨髓、睾丸、内脏和淋巴结侵犯较常见化疗仍然是必不可少的治疗手段NK/T细胞肿瘤具有不同寻常的表型特征含门冬酰胺酶的方案SMILE方案•Smile方案–Steroid(DXM)40mg,iv,d2-4–MTX2g/m2,iv,d1–IFO1.5g/m2,iv,d2-4–L-ASP6000U/m2,iv,d8,10,12,14,16,18,20–Etopside100mg/m2,iv,d2-4•G-CSF从第6天开始解救，wbc5000/mlYamaguchiM,etal.JCO,2011;29(33):4410-6SMILE方案疗效及毒性•CR率45%,CR+PR79%•1y-OS55%•毒性反应：92%患者出现IV度骨髓抑制，61%出现感染•8%出现早期死亡YamaguchiM,etal.JCO,2011;29(33):4410-6AspaMetDex方案•Steroid（DXM）,40mg,d1-4,po•MTX3.0g/m2,d1,ivdrip•IFO1.5g/m2,iv,d2-4•L-Asp6000U/m2,d2,4,6,8,im•Etopside100mg/m2,iv,d2-4JaccardA,etal.Blood,2011,117:1834-1839.•Smile方案–Steroid(DXM)40mg,iv,d2-4–MTX2g/m2,iv,d1–IFO1.5g/m2,iv,d2-4–L-ASP6000U/m2,iv,d8,10,12,14,16,18,20–Etopside100mg/m2,iv,d2-4近期疗效和毒性•近期疗效–18例可评价，14例获得缓解（78%），11例完全缓解（61%）–3例治疗中死亡•14例有效患者，6例在治疗结束后9个月内复发AspaMetDex方案远期生存中位OS12.2个月无效患者4.2个月有效后进展患者3.6个月PFS12.2个月晚期结外NK/T细胞淋巴瘤治疗GOLD方案Efficacyofgemcitabinecombinedwithoxaliplatin,L-asparaginaseanddexamethasoneinpatientswithnewly-diagnosedextranodalNK/T-celllymphomaG：gemcitabine1g/m2，d1，D8O：Oxaliplatin100mg/m2，d1L：L-Asparaginase10,000U/m2，d1-5D：dexamethasone40mg，d1-414-daycycle，AnnArborI/II期化疗后给予IFRT2008-2012新诊断的ENKTLGuoHQ,LiuL,WangXF,LinTY,etal.MolClinOncol.2014Nov;2(6):1172-1176GOLD方案GuoHQ,LiuL,WangXF,LinTY,etal.MolClinOncol.2014Nov;2(6):1172-1176GOLD方案3YsPFS57%3YsOS74%1YsPFS87%vs66%P0.0011YsOS98%vs75%P0.001GuoHQ,LiuL,WangXF,LinTY,etal.MolClinOncol.2014Nov;2(6):1172-1176