慢性移植物抗宿主病

慢性移植物抗宿主病内容

UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDCIBMTR:GVHD发病率RingdénO,etal.Blood.2009;113:3110-3118.NIH新的GVHD分类标准(2005)AcuteGVHDclassicacuteGVHDlate-onsetacuteGVHDChronicGHVDClassicchronicGVHDOverlapsyndromeNIH分类标准最重要的变化是以临床表现和器官受累的程度，而不是移植后时间来进行分类，这有利于临床医生作出更符合病理生理学改变的诊断和治疗策略FilipovichAH,etal.

Biol.BloodMarrowTransplant.11(12),945–956(2005).GVHDclassificationaftertheNIHconsensusconference

PavleticSZ,andFowlerDHHematology2012;2012:251-264cGVHD发病的危险因素AcuteGVHDOlderageofrecipientanddonorFemalemultiparousdonorMismatchedandunrelateddonorsPBSCproductDiseasetype:CML,Aplasticanemia↓HighCD34doseand/orT-celldoseSecondtransplantsDLIsCMV?影响cGVHD发病率的因素ClassificationProgressivepoorestprognosisQuiescentdenovo#1riskfactor:historyofacuteGVHDChangingriskfactorsOlderrecipientageDonors(unrelated,haploidentic)Non-myeloablativeconditioningPeripheralbloodstemcellsourceDonorleukocyteinfusions(DLI)Leeetal.,BiolBloodMarrowTransplant2003;9:215-33.慢性GVHD的临床表现大家应该也有点累了，稍作休息大家有疑问的，可以询问和交流9cGVHD:多形性的皮肤病变

cGVHD

cGVHD：口腔黏膜溃疡TreisterNetal.Blood2012;120:3407-3418Pérez-SimónJAetal.Haematologica2012;97:1187-1195不同类型cGVHD的预后MultivariateriskfactorprofilesacuteGVHDandchronicGVHDFlowersM,etal.Blood.2011;117(11):3214-3219)cGVHD危险度积分**采用危险度积分代替了既往局限性和广泛性的分类

OS：根据cGVHD危险度积分PavleticSZ,andFowlerDHHematology2012;2012:251-264内容

UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDcGVHD的病理生理学ThymicdamageanddefectivenegativeselectionDeficiencyofT-regsTGF-βandPDGFpathwaysmediatedfibrosisTh1/Th2/Th17paradigmcytokineDysregulatedB-cellandhumoralimmunityTakanoriTeshima,ASBMT2008The5TenetsofcGVHD中央免疫耐受：胸腺损害学说外周免疫耐受：T-regs细胞缺陷T-regsplayacriticalroleinperipheraltoleranceanddevelopmentofcGVHDCD4+lymphopeniaisakeyfactorinTreghomeostasis,andimpairedreconstitutionofTregscanresultinlossoftoleranceanddevelopmentofcGVHDAdoptivetransferofTregsandregulationtoincreaseTregsareconsideredtobeeffectiveclinicalstrategiesTGF-β和PDGF信号通路与纤维化cGVHDischaracterizedbyfibrosticchanges,TGF-β1levelsareincreasedsignificantlyinthepatientsTGF-βplaysanimportantroleinthegenerationandmaintenanceofTregsPDGFpathwaymayresultinautoimmuneeffects,andstimulatoryantibodiestothePDGFRwerefoundinallextensivecGVHDpatientsImatinibmayinhibitPDGFR,hasbeeninvestigatedfortherefractorycGVHDTheTh1/Th2/Th17的发育和平衡WeaverCT.Immunity.2006;24(6):677-88.TheTh1/Th2/Th17发育和平衡DonorCD4+TcellscanreciprocallydifferentiateintoTh1,Th2,andTh17cellsThatmediateorganspecificGVHD(Th1:gutandliver;Th2:lungandskin;Th17:gutandskin)Th1andTh17contributetothedevelopmentofcGVHDcGVHD：B细胞和体液免疫异常AstrongcorrelationbetweencGVHDandthepresenceofantibodiestoYchromosomeencodedhistocompatibilityantigensElevatedBcell-activatingfactor(BAFF)levels,whichpromotessurvivalanddifferentiationofactivatedBcells,havebeenobservedinpatientswithcGVHD.GeneticvariationinBAFFwasalsocorrelatedwithcGVHDcGVHDwasassociatedwithanincreasednumberofBcellsexpressinghighlevelsofToll-likereceptor9InvivodepletionofBcellsusingrituximabcansuppresstheprogressionofcomplexcGVHDcGVHDSummaryThymusHSCCD8CD4TregBInflammatorycytokinesFibrosingcytokinesAutoantibodyFibrosisandorgandysfunctionDeathfrominfection/organfailureAlloAuto内容UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDcGVHD的药物预防Mangarellietal.Hematologica.2003;88:315, Kansuetal.Blood.2001;98:3868. Chaoetal.BBMT.1996;2:96Ringdenetal.ExpHem.1985;13:1062 Fongetal.BBMT.2007;13:1201 Baronetal.BBMT.2007;13:1041cGVHD：系统治疗指征*Platelets<100,000/microliterorreceivingsteroidsattimeofdiagnosisofCGVHD‡Thebenefitsofgraft-vs.-tumoreffectandtheriskofCGVHDneedtobeweighted

Filipovic,BBMT2005;12:945-955Steroids:Sullivanetal,Blood1988;72.N=164Pred1mg/kgvsPred+AzathioprineNRM21%vs41%(p=0.03)Mostcommoncauseofdeath=relapseSteroids+CSA:Kocetal,Blood2002;100.N=287RCT:PredvsPed+CSANodifferenceinTRM,OS,relapse,needforsecondarycGVHDTxRelapsefreesurvivalbetterinprednisoneonlyarm

cGVHD:一线治疗Martin.IntJHem.2004;79:221 Stewartetal,Blood2004;104Vogelsang.BJH.2004;125:435 Lee,Blood.2005;105ProgressiononsteroidsWithin2-3monthsifnoimprovementonsteroidsInabilitytotapersteroidswithoutrecurrenceInabilitytotoleratesteroidsorcalcineurininhibitors(TTP)cGVHD:二线治疗SteroidpulseCSATacroMMFSirolimusECPPentostatinRituximabHydroxychloroquineThalidomide/RevlimidClofazamineAzathioprineATGTLILowdoseMTXDacluzimabInfliximabEtanerceptImatinibMontelukastcGVHD:二线治疗可选择药物cGVHD：二线治疗的疗效Leeetal,BBMT2002ResponseratesinsecondlinetherapyNishimoriH,ActaMedOkayama.2013;67(1):1-8.内容UpdateofknowledgesincGVHDProgressinpathobiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDKeratinocytegrowthfac