鼻型NK-T細胞淋巴瘤的診治PATHOGENESISOFNK/T-CELLLYMPHOMA1.Chromosomalabnormalities2.Geneticaberrations3.TheEpstein-Barrvirus(EBV)ChromosomalabnormalitiesDeletionofthelongarmofchromosome6BrJHaematol.1997;98:922-6.ChromosomalabnormalitiesBrJHaematol.1997;97:621-5.GeneticaberrationsFOXO3,PRDM1,TP53,CDKN2A,FAS,SHP1,TP73,andKITJClinExpHematopathol.2005;45:51-70.PATHOLOGYOFNK/T-CELLNEOPLASMS1.diffuseproliferationoflymphomacellswithanangiocentricorangiodestructivegrowthpattern2.Infiltrationofinflammatorycellsandsometimesaccompanynecroticchanges3.NKcellmarkers(CD2,cytoplasmicCD3(cyCD3),CD7,andCD56)4.CytotoxicmoleculessuchasTIA-1,granzymeB,andperforinDISEASEFEATURESOFNK/T-CELLLYMPHOMA1.originforENKL:thenoseandparanasalareaskin,gastrointestinaltract,etal.2.

StageI/II:Approximatelyhalfofthepatients3.NasalandextranasalENKLsinthesamecategoryofdiseaseaccordingtothecurrentWHOclassificationAnnOncol.2010;21:1032-40.NasalENKLmorefrequentlypresentsasalocalizeddisease,whereasextranasalENKLismorefrequentlydetectedatanadvancedstage.Blood.2009;113:3931-3937A.Limited-stage(I/II)diseaseB.advanced-stage(III/IV)diseaseBlood.2009;113:3931-3937TREATMENTOFEXTRANODALNK/T-CELLLYMPHOMA1.LimitedStages2.AdvancedStages,RelapsedorRefractoryState3.HematopoieticStemCellTransplantation(autologousandallogeneicHSCTs)Cancer.1995;76:2351-6.theexpressionofP-glycoprotein(P-gp)/MDRltheproductofthemultidrugresistance(MDR)1geneβ-actinMDR3MDRlDrug:vincristineanddoxorubicinJClinOncol.2000;18:54-63.JClinOncol.2000;18:54-63.(median56months)Treatmentfailure57/92(62%)(median8months)Relapsedrate14/61(23%)AnnOncol.2001;12:349-52.Newtreatmentstrategies,suchashigh-dosechemotherapywithstem-celltransplantation,earlyadministrationofradiationtreatment,orconcomitantchemo-radiotherapy,needtobeinvestigatedtoimprovethetreatmentoutcomes,particularlyinpatientswithpatientswithBsymptoms.1.Theplannedsequentialchemo-radiotherapy6/17(35%)2.Estimatedoverallthree-yearsurvival59%74patientsreceivingCT64CHOP(cyclophosphaminde,doxorubicin,vincristine,prednisone)orCHOP-bleo(CHOP+bleomycin)

9COBVP-16(cisplatin,vincristine,bleomycin,prednisone)

1COPP(cyclophosphaminde,vincristine,procarbazine,prednisone)37patientsreceivedRTafterCT.BeforeRT,20onetotwocyclesofCT,16threetofourcycles,1fivecyclesofCTJClinOncol.2006;24:181-9.1.LimitedStagesJClinOncol.2006;24:181-9.ResponseafterinitialtherapyRTvs.CT83%vs.20%(P=0.0001)ResponseaftertherapyRTandRT+CTvs.CT+RT92%vs.81%(P=0.387)1.LimitedStagesRTasprimarytherapyresultedingoodoutcomeinearly-stagediseaseJClinOncol.2009;27:5594-600.1.LimitedStagesJClinOncol.2009;27:5594-600.CR20/26(77%)OSat5years＞50%ORR21/26(81%)PFSat5years＞50%Overallsurvivaland(B)progression-freesurvivalofpatientstreatedwithradiotherapyandtwothirdsdoseofdexamethasone,etoposide,ifosfamide,andcarboplatin.JClinOncol.2009;27:5594-600.JClinOncol.2009;27:5594-600.Themostcommongrade3nonhematologictoxicitywasmucositisrelatedtoradiation(30%).Notreatment-relateddeathswereobserved.JClinOncol.2009;27:6027-32.1.LimitedStagesJClinOncol.2009;27:6027-32.JClinOncol.2009;27:6027-32.CCRTCR22/30(73.3%)ORR30/30(100%)CCRT+VIPDCR22/26(84.6%)OSat3years85.19%PFSat3years85.19%JClinOncol.2009;27:6027-32.Onlyonepatientexperiencedgrade3toxicityduringCCRT(nausea),whereas12of29patientsexperiencedgrade4neutropenia.2.AdvancedStages,RelapsedorRefractoryStateJClinOncol.2011;29:4410-6.ORR79%1-yearsurvivalrate55%A3-yearOSof50%HematolOncol.2013;31suppl.S1:175[abstract235].SMILEVS.historicalcontrolsL-asparaginase(Kidrolase,EusaPharma)6000units/m2ofbodysurfaceareaondays2,4,6,and8,intramuscularly(unlesscontraindicated),methotrexate3g/m2onday1,oraldexamethasone40mgfromday1to4.ROLEOFEBV-DNATopredicttheprognosisTopredictthedegreeofadversereactionsBlood.2011;118:6018-