医院培训课件：《外周T细胞淋巴瘤的治疗进展》

外周T细胞淋巴瘤的治疗进展主要内容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经验外周T淋巴瘤的分类PTCLisaheterogeneousgroupofaggressivematureT-/NK-celllymphomasPTCLdoesnotrefertoanatomicsites,butrathertotheinvolvementofmoremature(postthymic)TcellsvsprethymicorimmatureTcellsAdaptedfromSwerdlowSH,etal.WHOClassificationofTumoursofHaematopoieticandLymphoidTissues.2008.Non-Hodgkin’slymphomaT-/NK-cellneoplasmsB-cellneoplasmsT-cellprolymphocyticLeukemiaPrecursorLymphoidNeoplasmsCutaneousExtranodalLeukemicMatureT-/NK-cellneoplasmsNodalNK/TCLnasaltypeAdultT-cellleukemia/lymphomaSubcutaneouspanniculitis-likeTCLEnteropathy-associatedTCLHepatosplenicTCLAggressiveNK-cellleukemiaTransformedMFPrimarycutaneousgamma/deltaTCLPeripheralTCL-NOSAngioimmunoblasticTCLAnaplasticlarge-celllymphoma(ALK+/-)AggressiveT-LymphoblasticLeukemia/LymphomaPrimarycutaneousCD30+T-celldisordersMFT-celllargegranularlymphocyticleukemiaSézarySyndromeIndolentInternationalT-CellLymphomaProject.JClinOncol.2008;26:4124-4130.1314例PTCL和NKTCL的分布25.9%18.5%10.4%9.6%6.6%5.5%4.7%12.2%2.5%0.9%1.4%1.7%PeripheralT-celllymphomaAngioimmunoblasticNaturalkiller/T-celllymphomaAdultT-cellleukemia/lymphomaAnaplasticlarge-celllymphoma,ALK+Anaplasticlarge-celllymphoma,ALK-Enteropathy-typeTcellPrimarycutaneousALCLHepatosplenicTcellSubcutaneouspanniculitis-likeUnclassifiablePTCLOtherdisorders四川省肿瘤医院淋巴瘤病区截止2014年3月PTCL流行病学不同地域PTCL亚型相对发病率[1,2]总的发病率亚洲和加勒比地区更高1.SavageKJ.HematologyAmSocHematolEducProgram.2005;10:267-277.2.InternationalT-CellLymphomaProject.JClinOncol.2008;26:4124-4130.SubtypePercentage[2]NorthAmericaEuropeAsiaPTCL-NOS34.434.322.4Angioimmunoblastic16.028.717.9ALCL,ALK+16.06.43.2ALCL,ALK-7.89.42.6NK/TCL5.14.322.4ATLL(HTLV-1+)2.01.025.0Enteropathy-type5.89.11.9Hepatosplenic3.02.30.2PrimarycutaneousALCL5.40.80.7Subcutaneouspanniculitis-like1.30.51.3UnclassifiableT-cell2.33.32.4PTCL亚型及细胞来源PTCLSubtypeImmuneCellofOriginNK-celllymphomaNaturalkillercellsγδT-celllymphomaγδT-cellsALCLandPTCL/NOST-helperandT-cytotoxiccellsAITL/Tth-PTCL/NOST-follicularhelpercellsPiccalugaPP,etal.ExpertRevHematol.2011;4:415-425.PTCL的诊断10%PTCL诊断不正确大多数病人是III/IV期结外受累常见:皮肤、肝脏、脾脏、骨髓、外周血PTCL的诊断：MIC（形态学、免疫学和细胞遗传学）细针穿刺活检不能作为诊断依据，必须进行活检切除术1.VoseJ,etal.JClinOncol.2008;26:4124-4130.2.WarnkeRA,etal.AmJClinPathol.2007;127:511-527.3.SwerdlowSH,etal.WHOClassificationofTumoursofHaematopoieticandLymphoidTissues.2008.

4.KocjanG.JClinPathol.2005;58:561-567.ALCL,ALK+97%PTCL,unspecified75%ATLL93%Panniculitislike75%NasalNK/Tcell92%ALCL,ALK-74%Angioimmunoblastic81%Hepatosplenic72%Enteropathytype79%CutaneousALCL66%VoseJM,etal.JClinOncol.2008;26:4124-4130.专家的共识不同PTCL亚型的预后VoseJ,etal.JClinOncol.2008;26:4124-4130.OS(%)Time(yrs)010203040506070809010002468101214161820ALCL,ALK+

ALCL,ALK–

Allnaturalkiller/T-celllymphomas

PTCL,nototherwisespecified

AITL

AdultT-cellleukemia/lymphomaPTCLSubtypesALK+ALCLALK–ALCLPTCL-NOSAITLNK/TCLATLL5-yrOSrate,%704932323214Majorityofpatients(>85%)withmostcommondiseasesubtypesreceivedanthracycline-containingregimenInternationalT-CellLymphomaProject.JClinOncol.2008;26:4124-4130.OS(%)Yrs010203040506070809010002468101214161820ALCL,ALK+

ALCL,ALK-

AllNK/T-celllymphomas

PTCL-NOS

AITL

AdultT-cellleukemia/lymphoma含蒽环类方案治疗PTCL的疗效PTCL的预后指数TheIPIforNHLiscommonlyusedinPTCL[1]1.InternationalNon-Hodgkin'sLymphomaPrognosticFactorsProject.NEnglJMed.1993;329:987-994.2.GallaminiA,etal.Blood.2004;103:2474-2479.InternationalPrognosticIndexAllpatientsAge(≤60yrsvs>60yrs)SerumLDH(≤1xULNvs>1xULN)Performancescore(0or1vs2-4)Stage(IorII[localized]vsIIIorIV[advanced])Extranodalinvolvement(≤1sitevs

>1site)Age-adjustedindex(age

≤60yrs)Stage(IorIIvsIIIorIV)SerumLDH(≤1xULNvs>1xULN)Performancescore(0or1vs2-4)ThePITisalsoinuse[2]PrognosticIndexforPTCL>60yrsofageECOGperformancescore(score≥2)ElevatedLDHBonemarrowinvolvementTheIPIiscalculatedbasedonthesumofthenumberofriskfactorspresentatdiagnosis:0-1Low2Low/intermediate3High/intermediate4-5HighThePITisbasedonnumberofriskfactorspresentatdiagnosis:Group1:0riskfactor(62%5-yrOS)Group2:1riskfactor(53%5-yrOS)Group3:2riskfactors(33%5-yrOS)Group4:3-4riskfactors(18%5-yrOS)PTCL的治疗TheInternationalPTCLandNK/TCLStudy:AnalysisofTreatments多数PTCL或NK/TCL(除外ALK+ALCL)用含蒽环类方案不能获得生存受益InternationalT-CellLymphomaProject.JClinOncol.2008;26:4124-4130.PTCLAILTYrs018246810121416010080604020OS(%)Anthracyclineaspart

ofinitialtreatmentYes

NoP=.11Yrs018246810121416010080604020OS(%)Anthracyclineaspart

ofinitialtreatmentYes

NoP=.48传统含阿霉素的方案对PTCL无效PTCL未来？采用新的诱导化疗方案

CTOP，EPOCH,CEOP,CHOPE

noveldrugcombinationregimen?CONSOLIDATION?

Autologoustransplant?

Allogeneictransplant?MAINTENANCE???新药、靶向药物研发SurfaceAntigens/ReceptorsCD2CD4CD25CD30Chemokinereceptors...MicroenvironmentalFactorsAngiogenesisImmunomodulationViralpathogensCellularSurvivalMechanismsProteasomeinhibitionHDACinhibitionDeathreceptorsandligandsCell-cyclearrestSignaltransductioninhibitionPTCL治疗可能的靶点化疗方案的新尝试改良CHOP方案（含蒽环类药物）--EPOCH--HyperCVAD--CHOP/ICE;CHOP/IVE--ACVBP新组合化疗方案

--门冬酰胺酶为主方案联合放疗（NK/T细胞淋巴瘤鼻型）--IFO/VP-16/铂类/吉西他滨/MTX/Ara-C等

VoseJM,etal.JCO,2008;26:4124-30;NCCNguideline(2012);2012ASCO,abs8050SchmitzN,etal.Blood,2010;116:3418-25;DeardenCE,etal.Blood,2011;Sep26新药研发化疗药物靶向药物--单抗类药物--小分子靶向药物--免疫调节剂--ALK抑制剂年轻PTCL患者：GHGNHLSG的研究SchmitzN,etal.Blood.2010;116:3418-3425.18-60yrsofage,LDH≤UNVOtherMajorSubtypesALCL,ALK+/-Months020010080604020EFS(%)p=0.0034060801006xCHOP-14/21(n=41)6xCHOEP-14/21(n=42)Months020010080604020EFS(%)p=0.012406080100nonEtoposide(n=12)Etoposide(n=32)Months020010080604020EFS(%)p=0.004406080100nonEtoposide(n=41)Etoposide(n=103)Months020010080604020EFS(%)p=0.057406080100nonEtoposide(n=29)Etoposide(n=69)PralatrexateisselectiveantifolatedesignedtopreferentiallyaccumulateincancercellsEntryPralatrexateisselectiveforcellsthatexpressRFC-1,whichisoverexpressedonsomecancercellsrelativetonormalcellsAccumulationOncetakenupbycancercells,pralatrexatebecomespolyglutamylated,resultinginhighintracellulardrugretentionInhibitionPralatrexateactsonfolatepathwaytointerferewithDNAsynthesisandelicitcancercelldeath

SirotnakFM,etal.CancerChemotherPharmacol.1998;42:313-318.KrugLM,etal.ClinCancerRes.2000;6:3493-3498.WangES,etal.LeukLymphoma.2003;44:1027-1035.新药Pralatrexate的作用机制PROPEL研究:PhaseIIPralatrexateinRelapsed/RefractoryPTCL111patientswithrelapsed/refractoryPTCLPralatrexate30mg/m2weeklyfor6wksin7-wkcyclesVitaminB12andfolicacidgiventodecreasemucositisORR:32/109(29%);CR:11%;PR:18%MedianPFS:3.5mosMedianOS:14.5mosGrade3/4toxicityThrombocytopenia:32%O’ConnorOA,etal.JClinOncol.2011;29:1182-1189.PROPEL研究:肿瘤体积、有效时间和生存O’ConnorOA,etal.JClinOncol.2011;29:1182-1189.Patients-1001007550-25-75ChangeinTumorVolumneFromBaseline(%)Months0301.00.80.60.40.2Progression-FreeSurvival(probability)9121821Pralatrexate30mg/m2(6/7weeks)

n=109;70events

Median(months)3.5;95%

CI,1.7to4.8Months03010080604020DurationofResponse(probability)9121824Months0301.00.80.60.40.2Overallsurvival(probability)9151824-5002515246Pralatrexate30mg/m2(6/7weeks)

n=109;62events

Median(months)14.5;95%CI,10.6to22.5

6-month,75%;95%CI,65.7%to82.1%Pralatrexate30mg/m2(6/7weeks)

n=32;16events

Median(months)10.1;95%

CI,3.4toNE6152121126PleiotropicEffectsofRomidepsin:ANovel,PotentBicyclicHDACiGeneregulation[1]Histoneacetylation/transcriptioninduction[2]Proteinacetylation[3]Activationofapoptosis[4]Antiangiogenesis[5]Cell-cyclearrest[4]1.PeartMJ,etal.ProcNatAcadSciUSA.2005;102:3697-3702.2.BoldenJE,etal.NatRevDrugDiscov.2006;5:769-784.3.WangY,etal.BiochemBiophysResCommun.2007;356:998-1003.

4.SatoN,etal.IntJOncol.2004;24:679-685.5.KwonHJ,etal.IntJCancer.2002;97:290-296.Wk4Wk2Wk31221581Wk1Cycle1Wk1Cycle2Schedule:4-hrinfusion14mg/m2onDays1,8,and15every28daysCoiffierB,etal.JClinOncol.2012;30:631-636.RomidepsininRelapsed/RefractoryPTCL:TreatmentScheduleRomidepsinRomidepsinRomidepsinRomidepsinRomidepsininRel/RefPTCL:ORRsBestResponseCategory,n(%)IRC(N=130)Investigators(N=130)Objectiveresponse(CR/CRu+PR)33(25)38(29)Completeresponse(CR/CRu)19(15)21(16)CR13(10)19(15)CRu6(5)2(2)PR14(11)17(13)SD33(25)22(17)PD/notevaluable*64(49)70(54)CoiffierB,etal.JClinOncol.2012;30:631-636.*Insufficientefficacydatatodetermineresponseduetoearlytermination.RomidepsininRel/RefPTCL:DORandSafetyMedianDOR:17mosOf19patientsinCR/Cru,17(89%)hadnotprogressedatamedianfollow-upof13.4mosGrade≥3toxicitiesThrombocytopenia:24%Neutropenia:20%CoiffierB,etal.JClinOncol.2012;30:631-636.CoiffierB,etal.JClinOncol.2012;30:631-636.RomidepsininRel/RefPTCL:Kaplan-MeierPFSEstimate(IRC;AllPatients)Mos3633302724211815129630020406080100PFS(%)N=130Anti-CD30ADC:BrentuximabVedotin(SGN-35)ADC:3partsChimericantibodySGN-30Syntheticanalogue(MMAE)oftheantitubulinagentdolastatin10StabledruglinkerProposedmechanismofactionBindstoCD30InternalizedintothetumorcellMMAEisreleasedTumorcellundergoesG2/Mphasecell-cyclearrestandapoptosisPreclinicalactivityobservedbothininvitroandinvivoFranciscoJA,etal.Blood.2003;102:1458-1465.BrentuximabVedotin+化疗一线治疗ALCLI期临床试验:39pts高危ALCL(IPI≥2)orCD30+成熟

T-cell/NK-细胞淋巴瘤随机分为3组1.8mg/kgbrentuximabvedotinq3wX2cycles,thenCHOPx6cycles1.8mg/kgbrentuximabvedotin+CHPq3wforupto6cyclesDetermineoptimaldoseofbrentuximabvedotintobeusedincombinationwithCHPinthirdarmRespondersreceiveadditionalcyclesofbrentuximabvedotinmonotherapyORR:100%(26/26);CR:88%(23/26)BrentuximabvedotinMTDnotexceededat1.8mg/kg1DLT:grade3rashin6pts治疗相关并发症:恶心(58%),疲乏(50%),腹泻(50%),周围神经病变(38%),脱发(38%)FanaleMA,etal.ASH2012.Abstract60.ProB,etal.JClinOncol.2012;30:2190-2196.BrentuximabVedotininRel/RefSystemicALCL:MaximumTumorReduction(IRC)TumorSize(%change

frombaseline)-100-50050100IndividualPatients(n=57)BestclinicalresponseCompleteremissionPartialremission

Stabledisease

ProgressivediseaseHistologicallyineligibleSelectOngoingClinicalTrialsofFirst-lineTherapyforPTCLPhaseIIICHOP±alemtuzumabCHOPfollowedby±pralatrexatePhaseIICEOP/pralatrexateCHOP+everolimusCHOPvsGEM-PCHOP+romidepsinCHOP+lenalidomideCHOP+alemtuzumabCHOP+denileukindiftitoxCHP+brentuximabvedotinClinicalT.NCT00725231.NCT01420679.NCT01336933.NCT01198665.NCT01719835.NCT01280526NCT00453427.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);duration2-120mosMostresponsesby4-6wksCsAdosereduced:6pts(3renalinsufficiency,2fatigue,1hypertension)CsAdiscontinued:3pts(2renalinsufficiency,1thyroidcancer)OUTCOMEOF8RESPONDERS3aliveandNED(2mos,3.5yrs,and10+yrs)1:losttofollow-upaftera18-mosPR4deaths:1PD,1BMTrelated,1infection(?Rxrelated),1unrelatedICbleedOther:1lymphoproliferativedisorderAdvaniR,etal.LeukLymphoma.2007;48:521-525.*OnRx.Alisertib:InvestigationalAuroraAKinaseInhibitorResultsinmitoticdefectsAbnormalspindlesUnseparatedcentrosomesDelayedmitoticprogressionApoptosisorsenescenceUntreatedTreatedTreatedNCIOFNNHNOOHOFriedbergJ,etal.ASH2011.Abstract95.FriedbergJ,etal.ASH2011.Abstract95.Alisertib(MLN8237):AnAuroraAKinaseInhibitorII期进展期B-cell和T-cellNHLN=48ORR:32%CR:12%病理学诊断PTCL:57%DLBCL:20%;MCL:23%;转化FL:40%副作用:中性粒细胞减少,血小板减少,胃炎Alisertib的随机临床开放III期临床试验：复发难治PTCLPrimaryendpoint:ORR,PFSSecondaryendpoints:safety,CR,OS,TTPRelapsed/refractoryPTCLECOGPS0-2(N=354)*Choices:PralatrexateRomidepsinGemcitabineAlisertib5x10mgPOBIDon

Days1-7ofa21-daycycleInvestigator’schoice*ClinicalT.NCT01482962.PohlmanB,etal.ASH2009.Abstract920.Belinostat(PXD101):APan-HistoneDeacetylaseInhibitorPhaseIItrialinPTCLN=20ORR:25%CR:2PR:3DOR:5mosAEs:pruritus,edema,rashDamajG,etal.JClinOncol.2012;[Epubaheadofprint].苯达莫司丁复发耐药PTCL的多中心II期临床试验(BENTLY)：N=60(23ptsPTCL-U)方案:120mg/m2D1、2q3wORR:50%28%CR/CRuMedianPFS:3.6mosMedianOS:6.2mos最常见3/4AEs:中性粒细胞减少、感染、血小板减少DueckG,etal.Cancer.2010;116:4541-4548.来啦度胺II期临床试验：24PTCLPts.（N=24）ORR:30%(7/23)AllPRs 所有亚型都有效MedianPFS:96days MedianOS:241days AEs:中性粒细胞减少、疼痛、血小板减少、皮疹IshidaT,etal.JClinOncol.2012;30:837-842.Mogamulizumab(KW-0761):抗-CCR4（趋化因子受体4）单克隆抗体II期临床试验：入组ATLL患者N=28ORR:50%(13/26)CR:8/26MedianPFS:5.2mosMedianOS:13.7mosAEs:输注反应(89%),皮疹(63%)AITL复发后的治疗选择可考虑用药：romidepsin或pralatrexate其他标准挽救治疗方案临床试验假如诱导化疗达到CR2，可以考虑自体或异体干细胞移植系统性间变大细胞淋巴瘤（ALCL）发病特点2013年估算[1]:~70,000新发病例；1394-3487新发病例为系统性ALCL*任何年龄均可发病；男性多于女性；大多数患者表现为晚期疾病且存在B症状

[2]常伴有皮肤受累；通常表达CD30；1.SiegelRetal.CACancerJClin.2013;63:11-30.2.SavageKJ,etal.Blood.2008;111:5496-5504.*Basedon2%to5%ofallNHLcasesbeingALCLALK阳性的ALCL60%的ALCL存在ALK蛋白的过度表达

=ALK+典型

t(2;5)(p23;35)HubingerG,etal.ExpHematol.2003;31:226-233.NPM5号染色体ALK2号染色体NPM-ALK融合蛋白不同的融合蛋白

ALK蛋白表达ALK1ALCL:IPI和ALK状态与OSSavageKJ,etal.Blood.2008;111:5496-5504.ALK+ALCLALK-ALCLOS(%)Yrs010203040506070809010001356810121314112794P<.001IPI0,1IPI2IPI3IPI4,5OS(%)Yrs010203040506070809010001356810121314112794P<.001IPI0,1IPI2IPI3IPI4,5SibonD,etal.JClinOncol.2012;30:3939-3946.ALK表达与ALCL生存率Years2.51.00.80.60.40.2Progression-FreeSurvival(Probability)Log-rankP<.001512.52022.5ALK+ALCL

ALK-ALCLALK+

ALK-Years051.00.80.60.40.2OverallSurvivalinPts≤40Yrs(probability)7.512.517.522.564

7428%(18)

59%(44)72%(46)

41%(30)13.98(10.92toNR)

3.78(1.10to19.41)No.ofPatientsEventsCensoredMedianSurvival

(95%CI)7.5101517.52015102.5Log-rankP<.001ALK+ALCL

ALK-ALCLALK+

ALK-42

1719%(8)

12%(2)81%(34)

88%(15)NR(NRtoNR)

NR(NRtoNR)No.ofPatientsEventsCensoredMedianSurvival

(95%CI)Years2.501.00.80.60.40.2OverallSurvival(Probability)Log-rankP<.001512.52022.5ALK+ALCL

ALK-ALCLALK+

ALK-Years501.00.80.60.40.2OverallSurvivalinPts>40Yrs(probability)7.5152064

7420%(13)

51%(38)80%(51)

49%(36)NR(13.98toNR)

6.71(3.44to19.41)No.ofPatientsEventsCensoredMedianSurvival

(95%CI)7.5101517.517.512.5102.5Log-rankP<.0022ALK+ALCL

ALK-ALCLALK+

ALK-22

5723%(8)

63%(36)77%(17)

37%(21)13.98(10.92toNR)

4.97(1.99to8,31)No.ofPatientsEventsCensoredMedianSurvival

(95%CI)0ALCL治疗指南ALK-阳性患者的推荐方案诱导:CHOP-21或

CHOEP-21±RT巩固:若疾病缓解，则不用ALK-阴性或ALK-阳性患者的二线治疗临床试验联合化疗(如ICE,EPOCH,其它)单药治疗(如brentuximabvedotin[sALCLonly],alemtuzumab,pralatrexate,romidepsin,bortezomib,gemcitabine)ALK-阴性患者的推荐方案诱导:临床试验或联合CT±RT巩固:是NCCN.Clinicalpracticeguidelinesinoncology:non-Hodgkin’slymphoma.v.2.2014.PTCL-NOS基因表达谱PTCL-NOScanbeseparatedinto3subgroupsonthebasisofgeneexpressionprofiles(U1,U2,andU3)IthasnotbeenestablishedwhetherthesesubgroupscorrelatewithclinicaloutcomePreliminaryfindingsindicatethatPTCL-U1mayhaveaworseoutcomethanPTCL-U2or-U3BallesterB,etal.Oncogene.2006;25:1560-1570.MolecularSubgroupGeneExpressionSignatureU1Includedgenesinvolvedwithpooroutcomeinothertumors(CCND2)U2OverexpressionofgenesinvolvedinT-cellactivationandapoptosis(NFKB1,BCL-2)U3OverexpressionofgenesinvolvedinIFN/JAK/STATpathwayFailure-FreeSurvival(%)0102030405060708090100Yrs0123456789101112131415P<.001PTCL-NOSCD30+≥80%ALK-ALCLSavageKJ,etal.Blood.2008;111:5496-5504.CD30+PTCL-NOS的预后AgnelliL,etal.Blood2012;120:1274-1281TNFRSF8BATF3TMOD1Expressionvalues(DCt)Expressionvalues(DCt)Expressionvalues(DCt)1086420PTCLALCLALK-P=2.632e-111086420PTCLALCLALK-P=2.225e-1010864PTCLALCLALK-P=1.423e-071212RT-PCR对PTCL进行基因分型PTCL临床关键点必须有血液病理学专家参与需要仔细评估临床病史、预后资料、危险因素预后不良的类型需要考虑临床试验或新药的使用PTCL临床关键点标准的CHOP基本无效需要新药和新的联合化疗方案用于诱导或是复发基因表达谱可能会为我们确定新的靶点治疗应当包括诱导、巩固和维持治疗特定的患者需要PSCT治疗临床试验对PTCL治疗非常重要NCCN指南推荐结外NK/T淋巴瘤鼻型

化疗方案Combinationchemotherapy(L-a