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急性髓系白血病WHO分型及治疗魏辉魏辉中国医学科学院血液病医院（血液学研究所）WHO分型与分型FAB与WHO分型newlydiagnosedpatientswith“AMLBLOOD，2013121:2424-2431newlydiagnosedpatientswithAML,NOS.”与分型FAB与WHO分型NPM1andNPM1/CEBPApatientsBLOOD，2013121:2424-2431NPM1–andNPM1–/CEBPA–patientswithnewlydiagnosed“AML,NOS.”duetothelackofprognosticsignificanceofmultilineagedysplasiainpatientswithoutMDS-associatedcytogeneticfindingsandwithamutationofNPM1orbiallelicmutationofCEBPA87-89,thesemutationsnowsupersedethepresenceofmultilineagedysplasiaintheclassification.AML with mutated CEBPA or NPM1•CEBPA要求双突变，需要排除单突变•NPM1和CEBPA突变的AML诊断分型要优和突变的诊断分型要优先于伴有多系增生异常AML的分型。NPM1andMultilineagedysplasiaBlood.2010Dec23;116(26):6147-8CEBPAmutationAMLCEBPAmutationAMLJClinOncol28:2739-2747CEBPAmutation单突变双突变单突变双突变双突变双突变denovoAMLwithBCR-ABL1•一个新的建议分个新的建议分类•可能从TKI治疗中Ph+AML•可能从TKI治疗中获益CML-MBCPh+AMLAmJClinPathol2007;127:642-650Ph(+)AMLvsCML/BCL•Ph(+)AML常伴有免疫球蛋白及T细免疫球蛋白及T细胞受体基因的隐胞受体基因的隐性缺失。BrJHaematol.2013May;161(4):541-50AnnHematol(2016)95:1211–1221AML‐MRC•由于NPM1突变及CEBPA双突变常伴发由于NPM1突变及CEBPA双突变常伴发del(9q)，并且这种情况下的del(9q)没有预后意义因此dl(9)从定义MDS相关预后意义，因此，del(9q)从定义MDS相关的细胞遗传学异常中去除CEBPAandkaryotypeCEBPAandkaryotypeabnormalitiesabnormalitiesRFSOSBlood.2013;122(9):1576-1582NPM1andkaryotypeabnormalitiesEFSOSBlood.2009;114:3024-3032AMLwithmutatedRUNX1AML with mutated RUNX1•一个新的建议分类•主要见于细胞遗传学中危组，尤其是正常核型非复杂核型的高危组中发生率核型，非复杂核型的+8。高危组中发生率低。RUNX1突变与MDS相关的细胞遗传学改变没•RUNX1突变与MDS相关的细胞遗传学改变没有相关性JClinOncol2011,29:1364-1372RUNX1andkaryotypeRUNX1 and karyotypeKtTtlRUNX1ttdRUNX1ildKaryotypeTotalRUNX1-mutatedRUNX1-wildFavorable590(0.0)59(100.0)Intermediate32748(147)279(853)Intermediate32748(14.7)279(85.3)Unfavorable668(12.1)58(87.9)Normal23032(13.9)198(86.1)Simple16919(11.2)150(88.8)Complex535(9.4)48(90.6)-7/7q-103(30.0)7(70.0)+8226(27.3)16(72.7)+21112(182)9(818)+21112(18.2)9(81.8)-5/5q-10(0.0)1(100.0)+1130(0.0)3(100.0)+1310(0.0)1(100.0)Blood.2009;114:5352-5361RUNX1mutationRUNX1mutation•发生率：5.6%，（6.3%inCNAML）•CR：RUNX1突变型和野CR：RUNX1突变型和野生型的CR率分别为60.4%and73.4%60.4%and73.4%（P=0.055)JClinOncol2011,29:1364-1372RUNX1mutationRUNX1mutationRFSOSJClinOncol2011,29:1364-1372AML, not otherwise specified•急性红白血病（AML,从分类中删erythroid/myeloidtype从分类中删除除•纯红血病（Pureerythroidleukemia）仍然保留在AMLNOS亚型中仍然保留在AML,NOS亚型中。BMerythroidprecursorsMyeloblast%inBM(orPB)PriorTherapyRecurringgeneticabnormalityMeetscriteriaforAML-MRCFourtheditiondiagnosisUpdatedfourtheditiondiagnosis≥50%NAYesNANATherapy-relatedmyeloidneoplasmTherapy-relatedmyeloidneoplasm≥50%≥20%NoYesYesAMLwithrecurringAMLwithrecurring≥50%≥20%NoYesYesAMLwithrecurringgeneticabnormalityAMLwithrecurringgeneticabnormality≥50%≥20%NoNoNoAMLwithMRCAMLwithMRC≥50%≥20%NoNoNoAMLwithMRCAMLwithMRC≥50%≥20%NoNoNAAML,NOS,acuteerythroidleukemiaAML,NOS(nonerythroidsubtype)(erythroid/myeloidtype)erythroidsubtype)≥50＜20%,but≥20%ofNoNoNAAML,NOS,acuteerythroidleukemiaMDS≥20%ofnonerythroidcellserythroidleukemia(erythroid/myeloidsubtype)≥50%＜20%,andNoNoNAMDSMDS＜20%ofnonerythroidcells≥80%immature＜20%NoNoNAAML,NOS,acuteAML,NOS,acuteerythroidprecursorswith≥30%proerythroblasts＜20%NoNoNAAML,NOS,acuteerythroidleukemia(pureerythroidtype)AML,NOS,acuteerythroidleukemia(pureerythroidtype)GtilttiiAMLGenetic alteration in AML‐M6(WHO2008)M6(WHO2008)Leukemia(2013)27,1940–1943;11genesandcounting11genesandcounting•HematologicmalignanciesonlyAML:CEBPAMDS/AML:DDX41MPNs/AML:ATG2B/GSKIPMPNs/AML:ATG2B/GSKIP•Cytopeniasand/orplateletdysfunctionFPD/AML:RUNX1MDS/AML:GATA2Thrombocytopenia:ETV6,ANKRD26Bfil•BonemarrowfailuresyndromesTelomeresyndromes:TERT,Blood.2016Feb25;127(8):960-1TERC,ACDAA/MDS:SRP72FamilialAMLwithgermlineFamilial AML with germlineCEBPA mutationsBlood.2015;126(10):1214-1223MPAL•诊断AML或ALL，并不需要按照MPAL的系列诊断AML或ALL，并不需要按照MPAL的系列标志标准进行分型诊断。•对于两群细胞的白血病，每一个符合T、B对于两群细胞的白血病，每个符合T、B或髓系标准即可，不一定要有特异性系列标志表达标志表达AMLM0AML‐M0•例，FCM,oneblastpopulation:cCD3dim,CD13dim,CD33,CD34,CD56bright,and,,,g,CD117.•Negative:CD1aCD2mCD3CD5CD4•Negative:CD1a,CD2,mCD3,CD5,CD4,CD7,CD8,CD11b,CD11c,CD14,CD16,C1C61C6CD41,CD61,CD64,glycophorinA,HLA-DR,MPO,andTdT•核型：46,XYAmJClinPathol2015;144:361-376BPDCNBPDCNAML的治疗成人的诱导治疗成人AML的诱导治疗NCRIAML17GOELAMSLAM-2001DA45DA90=DA60IA8X5=IA12=ECOG1900DA50X5JALSGAML201NEnglJMed2009;361:1249-1259.Blood.2015;125(25):3878-3885JALSGAML201Blood.2011;117(8):2358Leukemia.2014;28(2):440-4433蒽环剂量与NPM1突变蒽环剂量与NPM1突变Blood.2016;127(12):1551-1558CALGB8525CALGB8525INDUCTIONINTENSIFICATIONRAAra‐C, 4 coursesAML1088DNR 45mg/m2, d1‐3(≤60y)30mg/m2, d1‐3(＞60y)CRn=693NDO100mg/m2, d1‐5400mg/m2, d1‐5n=1088Ara‐C 200mg/m2, d1‐7n=693MIZ3g/m2/12h, d1, 3, 5 ZEN Engl J Med. 1994 Oct 6;331(14):896‐903成人AML的巩固治疗成人AML的巩固治疗MRCAML15诱导两疗程MACEMidACMRCAML15CAGB9222HDACCTX+VP16MTZ+AZQDA(45)诱导两疗程MACEMidACCAGB9222HDACCTX+VP16MTZ+AZQDA(45)ALFA9802德国Amsa+Ara-cTSCTSC德国AML2003MAC(1g/m2)MAMACMACDA双诱导血研所DA/MA中剂量X2MAHAHADJClinOncol.2013;31(27):3360JClinOncol2013;31:2094-2102Blood.2011;118(7):1754-1762Blood.2005;105:3420-3427大剂量阿糖胞苷的剂量MRCAML15MRC-AML15JClinOncol.2013;31(27):33603g/m2vs1.5g/m2Ara-cP=0.6P=01P0.1JClinOncol.2013;31(27):3360AML缓解后应予几个疗程的巩AML缓解后应予几个疗程的巩固治疗固治疗MRCAML15M