慢性移植物抗宿主病內(nèi)容

UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDCIBMTR:GVHD發(fā)病率RingdénO,etal.Blood.2009;113:3110-3118.NIH新的GVHD分類標(biāo)準(zhǔn)(2005)AcuteGVHDclassicacuteGVHDlate-onsetacuteGVHDChronicGHVDClassicchronicGVHDOverlapsyndromeNIH分類標(biāo)準(zhǔn)最重要的變化是以臨床表現(xiàn)和器官受累的程度，而不是移植后時間來進行分類，這有利于臨床醫(yī)生作出更符合病理生理學(xué)改變的診斷和治療策略FilipovichAH,etal.

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

PavleticSZ,andFowlerDHHematology2012;2012:251-264cGVHD發(fā)病的危險因素AcuteGVHDOlderageofrecipientanddonorFemalemultiparousdonorMismatchedandunrelateddonorsPBSCproductDiseasetype:CML,Aplasticanemia↓HighCD34doseand/orT-celldoseSecondtransplantsDLIsCMV?影響cGVHD發(fā)病率的因素ClassificationProgressivepoorestprognosisQuiescentdenovo#1riskfactor:historyofacuteGVHDChangingriskfactorsOlderrecipientageDonors(unrelated,haploidentic)Non-myeloablativeconditioningPeripheralbloodstemcellsourceDonorleukocyteinfusions(DLI)Leeetal.,BiolBloodMarrowTransplant2003;9:215-33.慢性GVHD的臨床表現(xiàn)大家應(yīng)該也有點累了，稍作休息大家有疑問的，可以詢問和交流9cGVHD:多形性的皮膚病變

cGVHD

cGVHD：口腔黏膜潰瘍TreisterNetal.Blood2012;120:3407-3418Pérez-SimónJAetal.Haematologica2012;97:1187-1195不同類型cGVHD的預(yù)后MultivariateriskfactorprofilesacuteGVHDandchronicGVHDFlowersM,etal.Blood.2011;117(11):3214-3219)cGVHD危險度積分**采用危險度積分代替了既往局限性和廣泛性的分類

OS：根據(jù)cGVHD危險度積分PavleticSZ,andFowlerDHHematology2012;2012:251-264內(nèi)容

UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDcGVHD的病理生理學(xué)ThymicdamageanddefectivenegativeselectionDeficiencyofT-regsTGF-βandPDGFpathwaysmediatedfibrosisTh1/Th2/Th17paradigmcytokineDysregulatedB-cellandhumoralimmunityTakanoriTeshima,ASBMT2008The5TenetsofcGVHD中央免疫耐受：胸腺損害學(xué)說外周免疫耐受：T-regs細胞缺陷T-regsplayacriticalroleinperipheraltoleranceanddevelopmentofcGVHDCD4+lymphopeniaisakeyfactorinTreghomeostasis,andimpairedreconstitutionofTregscanresultinlossoftoleranceanddevelopmentofcGVHDAdoptivetransferofTregsandregulationtoincreaseTregsareconsideredtobee?ectiveclinicalstrategiesTGF-β和PDGF信號通路與纖維化cGVHDischaracterizedby?brosticchanges,TGF-β1levelsareincreasedsigni?cantlyinthepatientsTGF-βplaysanimportantroleinthegenerationandmaintenanceofTregsPDGFpathwaymayresultinautoimmunee?ects,andstimulatoryantibodiestothePDGFRwerefoundinallextensivecGVHDpatientsImatinibmayinhibitPDGFR,hasbeeninvestigatedfortherefractorycGVHDTheTh1/Th2/Th17的發(fā)育和平衡WeaverCT.Immunity.2006;24(6):677-88.TheTh1/Th2/Th17發(fā)育和平衡DonorCD4+Tcellscanreciprocallydi?erentiateintoTh1,Th2,andTh17cellsThatmediateorganspeci?cGVHD(Th1:gutandliver;Th2:lungandskin;Th17:gutandskin)Th1andTh17contributetothedevelopmentofcGVHDcGVHD：B細胞和體液免疫異常AstrongcorrelationbetweencGVHDandthepresenceofantibodiestoYchromosomeencodedhistocompatibilityantigensElevatedBcell-activatingfactor(BAFF)levels,whichpromotessurvivalanddi?erentiationofactivatedBcells,havebeenobservedinpatientswithcGVHD.GeneticvariationinBAFFwasalsocorrelatedwithcGVHDcGVHDwasassociatedwithanincreasednumberofBcellsexpressinghighlevelsofToll-likereceptor9InvivodepletionofBcellsusingrituximabcansuppresstheprogressionofcomplexcGVHDcGVHDSummaryThymusHSCCD8CD4TregBInflammatorycytokinesFibrosingcytokinesAutoantibodyFibrosisandorgandysfunctionDeathfrominfection/organfailureAlloAuto內(nèi)容UpdateofknowledgesincGVHDProgressinpathophysiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDcGVHD的藥物預(yù)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：系統(tǒng)治療指征*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:一線治療Martin.IntJHem.2004;79:221 Stewartetal,Blood2004;104Vogelsang.BJH.2004;125:435 Lee,Blood.2005;105ProgressiononsteroidsWithin2-3monthsifnoimprovementonsteroidsInabilitytotapersteroidswithoutrecurrenceInabilitytotoleratesteroidsorcalcineurininhibitors(TTP)cGVHD:二線治療SteroidpulseCSATacroMMFSirolimusECPPentostatinRituximabHydroxychloroquineThalidomide/RevlimidClofazamineAzathioprineATGTLILowdoseMTXDacluzimabInfliximabEtanerceptImatinibMontelukastcGVHD:二線治療可選擇藥物cGVHD：二線治療的療效Leeetal,BBMT2002ResponseratesinsecondlinetherapyNishimoriH,ActaMedOkayama.2013;67(1):1-8.內(nèi)容UpdateofknowledgesincGVHDProgressinpathobiologyofcGVHDTreatmentforcGVHDNoveltherapeuticstrategiesofcGVHDKeratinocytegrowthfac