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【2017 ASH】关于慢性粒细胞白血病的研究精选

  

  ҰἤøƼTKIԽԽϸѪCMLߴл棬ԸơĿǰٵIJܡҩչͣҩ⣬ʱʹٴҽʦǰٿĵ58ѪҺУϸCMLصо½չĽеоȵܽ¡


  ֪2ȷѧӦDMRCML-CPжɳƺ40%~60%άƻ⣨TFRKad-owakiȹ87໼ߣλ13.4£жƺ5360.9%άMR34󲿷6ɥʧMR94.1%ɥʧMRƺٴλMRλʱΪ2.2£ʹDMRάֳ10꣬жԿܸӦȡIJԾ簲ȫжƣԱزӦķ


  DASFREEо31ܴɳƻDMR2ijCML-CPߣʾж1ʱҪѧӦMMR¼ʾΪ63%ƺػѧӦͣҩӦܣͣҩ֢״ʵ͡


  D-STOP鹲54άDMR2жϴɳƵĻߣλ16.2£20TFRΪ62.9%󲿷ָĻ߷жƺ6ڣиɳƺӦãԺŮԵ޲죻CD4+CD8-ϸ23.1%CD3-CD56+ϸ40.1%CD16+CD56+35.6%CD57+CD56+26.6%Ļߣͣҩ12º޲ʸߡ


  Hughes54CMLߣʾTFR߾нǿCTL߷ӦNKϸнϸߵЧӦͳϸͣϸMDSCs١֤ʵNKϸˮƽάTFRdzҪǿNKϸCTLЧӦӦNK KIR2DL2/DL3/DS2ı͵MDSCܴٽάTFRͨЧӦӦCD56dim CD57+NKBMI-1 CTLӦKIRƼTFR


  Euro-SkiоУ448ƵĻߣʾ䡢ԱDMRǷʵMR4.5SokalEUROEUTOSELTSֵһֹͣƺ6µMMR״̬ԣƳʱͣҩǰMR4ijʱ6µMMR״̬ԡ5.8ߣ6޷ѧڣMRFSΪ65.5%5.8ߣ6MRFSΪ42.6%ɼù淶ķѧ⣬CMLߴͶTKIͣҩǺȫģҿʵָMRFS


  PagliardiniļǰֲչΪչڵijCMLߣʧܺTKIƺȷѧӦʵʩ2ͣҩ״ͣҩƣ2ͣҩMMRɥʧ󶼷6~12£ʾԱ䡢׶ΡԤ֡ǰԤ¶ʼTKIںϻάʱԵ2ͣҩٴӰ죻״ͣҩǰøںϻʱ2ͣҩ͵޷ѧءʾ״ʧܣCMLȻɰȫҳɹֹͣ2TKIơ


  SIMPLICITY鹲238һTKIתɶTKIƵCML-CPߣһ߸ڻҩжƵĻУ1/3Ҫǰ3ڣ벻ҩĻȣڻҩŮԾӶࣻTKIǻҩҪԭڻҩأҩǻҩĵ2ԭ򣬴󲿷ַڻҩͽƵĻߣҩڽƵĻб


  һ6ĿԡۡĵĢУ59CML-CP߽ܴɳ100mg/dֱչ򲻿ܶԷӦҩܵйCML-CP߽ܴɳƵijڰȫԡ661%CML-CPԼơҩزӦΪ74.6%20.3%Ļ3~4ҩزӦ16.9%ҩزӦ16.9%ѪҺԲӦ3~4Ϊ11.9%ҩزӦǻҺ25.4%3~43.4%1.7%ĻǻҺжϴɳƣζѪѹΪ8.5%Ѫ˨Ϊ1.7%ʾҩܵйCML-CPߣܴɳƵijڰȫá


  TIDELL-Ҫоһ߸δʵMMRʵ36Ŀ꣩CML-CPߣ60ʱ59%ĻʵMR4.5NILSwо3819ºMMRδCMRMR4.5CML-CPߣ400 mg bid24£2052.6%ʵCMRһתΪ/ڣʾҩCML-CP߻400 mg bidΪѡƲԡGugliottaȹ345һƵĻߣл߾ø߷ѧӦʣỼߣ18~49꣩ļչʸΪΪѪأ仼ߣ65꣩¼ѪأѪ¼ӷӦߣʣ50껼ӦעԤѪ¼ỼӦעα⼲չ


  4. ȽCML-CP׼뼤ƵоJALSGCML207о


  JALSGCML207оУ߷ֳ2飬һΪŷްѪ磨ELNƼı׼һΪΪļ3δʵCCyRMMRΪ600 mg/dҪо12ʱʵMMRʡоΪļɻøõϸŴѧӦ𣬵󲢲ʵָõķѧӦ𣻸ƵʵͣҩʿܵƷЧơʲƼļӦݻѪӦҩǻٴֵѷʽ2TKI


  IFN-гߵãTKIϿܻTFRʡIlanderȹ40ϵCMLߣôɳ100 mg qd3ºIFN-12º½ܴɳᵥҩơʾǰȣɳᵥҩʹNKϸƵߣٽNKϸ죬Bϸ½ƻߵĩֻЧӦCD45RA+ϸTemra࣬ЧӦ䣨EMTϸ½IFN-ϲδӰNKϸNKϸTϸ͵Ӱɳ෴֤ʵɳIFN-ƿɵԺͻϵͳɳյijϸIFN-ڽϸתɲ͡


  ABL001Ŀǰڿ׶εCMLPh+ALLBCR-ABLƼɽBCR-ABLøṹĴ״ṹ谭ޢABL1BCRںϡTKIҩBCR-ABLͻ䣬ABL001ͨATPʽԡTKIʹãABL001ڰѪǰϸҩ¡ij֡HughesоУܡ2TKIʧܵڡڡCML߻1TKIʧܵPh+ALLߣͨҩABL001TKIãʾABL001ãЧ־ãCML-CPƼ40mg bid


  GԴPhFISHͣPCRȷֶοɼ⵽BCR/ABL1Ph-BCR-ABL1+CMLTKIƸ໼ߵٴݱȽѷGhorabȷ9໼ߣλ34꣬Ph+ữSokal֣8ͷգ1߷գ4ᣬ2ôɳᣬ2ᣬ1ᡣ3ھCHR8CCyR66ڻCCyR712ڻMMR7MMR4.552ꡣλ79£4BCR-ABL1ﲻɲ⣬1άMMR1תΪڡʾPh-BCR-ABL+CML߽ᣬսϵͣTKIӦãڽֽΪ롣


  ѪϸSHHźͨ·BCR-ABLCMLҪSMOSHHźͨ·еĵڵףомBCR-ABL+ϸģеļ̡TurnerоʾԭʼCML-CPϸ߱SMOGLI2ӦCML-CPϸGLI2ת¼ˮƽӣɴ˿ΪԤTKIЧ־Ӧϸ/ǰϸSMOƼӦ߸ΪУʾSHHͨ·TKIҩDZڻƣBCR-ABLSHHͨ·˫ΪCMLҩ뼲չṩ˺˼·


  BP1001Ϊ֬ϷѾᣬCMLϸCMLֲAsh-izawa5CMLڻߣ2ϲT315Iͻ䣬ӦBP100 15mg/m2ÿܸҩ2Σiv2~3hҩ4ܡʾBP1001ɼԼҩCMLϸĸƣɳCMLϸǿ2~62T315IͻCMLߣƹаѪϸ֤ͣʵBP1001пҩCMLϸԣҿǿɳЧ


  NteliopoulosȹѼ100½ϵCMLз62ݣ2TKI38ݣ3BCR-ABLISΪӦ56Ӧ44ϸͻУASXL1IKZF1CREBBPƵߡطʾSokalϸͻķٴ־иӰ졣382TKIУϸͻϸͻSokalֶڡ桢޽չ棨PFSӰ졣ֳϵͻ2TKIƻߵڡ桢PFSӰ졣֤ʵϸͻԤƽϲ桢ҩʧܼչɸѡܴ2TKIһлĻȺ壬2TKIƺЧ˷ЩͻĽϲԤ󣬵ҪڸĻ߶нһ֤


  ϸŴѧ¡ݱ䣨CECMLһ֪ķأϲٴԤأԤҪTKIδȷоеҪ;쳣+8+19i17qPhȾɫ塣CE6CCyRڰCEߣ3CHRCCyRۻʺMMR죻2MR4.0MR4.5ʱϸŴѧƺӰ5꼲תʡʧʡ¼ʡCEΪҪ;Ⱦɫ쳣ӦʼӰ졣ʾCEƺӰٴ֡


  󲿷CMLBCR-ABL1ںϻںϵe13a2b2a2e14a2b3a2Ҫӷʽʹһת¼ķӦءBCR-ABL1ת¼Ͷڽ2TKICMLԤӰϢΪޡGIME-MACML鹲328CML-CPߣʼΪ300 mg bid400 mg bid124e13a2174e14a2302;СλΪ60£e13a2e14a2߱Ƚϣ12MMRֱΪ66%72%36MR4.0ֱΪ56%66%2ת¼ͻߵӦ뵥e14a2Ҫںߡ2黼ߵMMRMR4ۻڵe13a2ߣPFS棨OS졣e13a2ͻֳ߳Ӧٴֵƣ۲쵽IJСҲڸĻ߶пչо


  ThanȻعԷ¼µ2001-062014-11ȷ1ڽһCML-CPߣELTSηΪΣ顢Σ顢Σ飬10OSֱΪ50%82%93%10PFSֱΪ50%84%89%10CMLʷֱΪ43%9%3%BIMȱʧBIMȱʧȣ10OSֱΪ75%89%10CMLʷֱΪ16%4%֤ʵELTSֿԤCMLʲȷCMLΣߣŴѧBIMȱʧ̬ڷǸΣннһֲ㣬ȷCMLȺ


  NKG2DһֱNKϸϵļ塣оNKG2D2ֵLNK1HNK1䷢ֹSNPHaraȷ31ܴɳһƵCMLߣ־HNK1͵Ļʵָ졢ߵMR4.5ʣ죩ʾɳNKG2D HNK1NKϸ̼ǿLNK1ͣʵָȷѧӦˣݻNKG2Dͽи廯ҩCMLƿܾҪ壬TKIͣҩопֹɳʱ


  NCT01464411ΪһűǩġǰհԢٴоּڷTϸTregԻߵĶ̬Ӱ죬ڴɳеá2011-062012-06ε52ϵCML-CPߣôɳ100 mg qdƣ36¡2CML޹ص޼չɳ12TregϸDMRйأ18ʱͳѧ塣NKϸ̶ֻTregıʸأʾɳTregNKϸյֻҪáڽʾɳΪϵCML-CPһƷߴﵽDMRĽ죬ҴɳDMRйصѪTregΪԤҪĿһԤ־


  Klil-Drori246ΪCMLĻߣͨTKIƺʵʱPCRtPCRsԤ⼲25¡tPCRsΪ2~4£11~13º͵17~19½PCR֤ʵ1~2tPCRsĻ25´ﵽMMRأ3tPCRsĻߴﵽMMRıֵߡtPCRsܻӻԣɸѡʧܵĻ߸ʱתTKI


  Samȹ484TKIƵCMLߣλ66£Ѫ¼Ϊ53%иѪѹ42%ɲ루11%Ѫ˨¼Ϊ7%Ƚϣ23TKIѪܺͶѪ˨¼ķʸߣ᣾ɳ/᣾᣻Խ󣬷ԽߡFranklin֤ʵƵCMLߣ򲡻Ѫ֬ڴɳᡣ


  ZhuоʾPFKFB3ƼTKIҩCMLϸTKIԣCMLϸֳϸֲС


  һЩµĵͻἰTKIҩͻT315Mͻ䣬Ϊˮƽҩͻ䡣WangȷSKLB-5182ҩ3045mgkg-1d-1ֳ30mgkg-1d-1޷ƣSKLB-518 45mgkg-1d-1ЧBCR-ABL1ΰе㣨CrklStat5ϸСģоδضԡ


  LiuȻعо2004-062015-03ڼTKIƵ451CML-CPߣPh+Ⱦɫ쳣ACAȣPh+ACAߵCCyRۻʸͣʵCCyRʱͳѧ壻ʱǷPh+ACAʵҪѧӦӰ죻ƹгPh+ACAPh-ACAACAȣOSEFSPFS̡֤ʵʱƹгPh+ACAԽTKIƵCMLԤиӰ졣


  Jiangʾ1143TKIƵCML-CP껼ߣ27%Ļ߰в֢껼иCCVDͣ򣩴лۺdz֢֢Ӱ컼߹ճͽHRQoLҽHRQoLCML֢Ҫ


  Jiang2015-092016-06еһǸԤ桢ѡʾʾ߹ǵҪTKIıߡüزӦԼճͻĹǡCML֪ʶʵݵĽ͡ҽʦǵҪTKIѡ񡢼⡢TKIҩԭкͷҩ֮Ļ⡣TKIߡҩзTKIͣҩTKIزӦͳЧCMLҽʦҪǵ㡣߹ǵڲ죬ҽʦӦӹעߵĹǵ㣬ԸCMLߵںгҽϵĽ


  TKICML࣬ǶһµĹ۵㼰ƶԲߡҪΧCMLƽչŻTKIҩתTKIưȫԼͣҩл㱨֮һо룬ڴCMLȡøijɹܽ׼ѧø໼߻ֶΡ


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