慢性粒细胞白血病的诊断与治疗进展

1、[]2011-06-28[],,doi:1013969/j1issn11673-1409120111081099(,510515)[]介绍了慢性粒细胞白血病(ChronicMyelogenousLeukemia,CML)不同病期的诊断标准分析和比较了治疗CML的各种方法展望了CML治疗的后续发展方向[]慢性粒细胞白血病;诊断;治疗;进展[]R733172[]A[]1673-1409(2011)08-0225-04(ChronicMyelogenousLeukemia,CML)CML,,95%Ph,t(9;22)(q34;q11),/bcr/abl[1](chronicphase,CP)(acceleratedphase,AP)(blasticphase,BPblastcrisis,BC)CML(Ph+)(bcr/abl),,[2],,CML1诊断标准CMLbcr-abl[3]111(CP)CP:¹;º,,+10%,,;»,,10%;¼Ph90%;½bcr-abl90%~100%;¾-(CFU-GM)112(AP)AP:¹/,;º10%;»20%;¼;½Ph;¾CFU-CM,;¿113。

2、(BP)BP:¹++20%;º+30%;»+50%;¼2治疗211(BUS)(HU)CML,,,[4]#225#()2011888JournalofYangtzeUniversity(NatSciEdit)Aug12011,Vol18No1821221211干扰素A-DNA(IRF),(FAS),PhHLA,T[5]:A-5@106IU/(m2#d),,2~3,,1821212阿糖胞苷(Ara-C)Ara-C,DNA:Ara-C100mg,1/12h,5~7d,Ara-C10~20mg,,7~14d21213高三尖杉酯碱(HHT)HHT,M1D1AndersonHHTCML,Ph+CMLbcr/abl,CML[6]:HHT25mg/(m2#d),5~7d14d213,CML,922,Pht(9,22)(q34,q11),bcr-abl[7],p210,,,,1TKIsCCyR%TKICMLCPAPBP7520109595452030503030TKICML(80%)(CCyR),1[8],CCyR[9],CML,,[10],/0TKI()Abl,TKIabl[11]21311主要治疗药。

3、物1)(Imatinib)()(TKI),bcr-abl,abl,,CML2004(NCCN),CP[12]:400~600mg/d,90%,50%,30%3612,18CCyR,,[13]2)TKIs,bcr-ablATP,PhCML,[14]:¹TKIs;º;»,[15]3)CML,A-[20mg/(m2#d)],CMLCP,,21312TKIs耐药研究进展CMLbcr-abl[16],,bcr-abl,,,[17],#226#()20118,TKI,,,/[18]21313疗效预测1)TKIs,OCT-1[19],bcr-ablOCT-1,TKIs[20]2)TKImRNA[21],[22],63)BCR-ABL[23],3PCRbcr-abl,,,4)ABL,,[24],1/4[25],:¹;º,,;»;¼21421411自体干细胞移植CP540%,CPBP,CP4,130%[26]3~5,,,[27]21412异基因造血干细胞移植(Allo-HSCT)Allo-HSCTCMLPhCML[28],,CMLCP,560%~80%,APBP40%10%~20%,,CML(),[29。

4、]3展望CML,,CML,¹TKIs,,?,?º,ABL,;»¼T315I[][1],1[J]1,2006,19(3):190-1921[2]ODwyerME,DrukerBJ1Recentadvancementsinthetreatmentofchronicmyelogenousleukemia[J]1Blood,2002,53:369-3811[3],1[J]1,2006,20(4):80-851[4],1[J]1,2010,21(8):1378-13791#227#88:[5],,1[J]1,2008,28(1):203-2051[6],,1[J]1,2008,29(4):28-301[7]DeinigerMW,GoldmanJM,MeloJV,etal1Themolecularbiologyofchronicmyeloidleukemia[J]1Blood,2010,96(3):343-3561[8]ShahNP,KimDW,KantarjianH,etal1Potent,transientinhibitionofBCR-ABLwithdasatinib100mgdailyac。

5、hievesrapidanddu-rablecytogeneticresponsesandhightransformation-freesurvivalratesinchronicphasechronicmyeloidleukemiapatientswithresist-ance,suboptimalresponseorintolerancetoimatinib[J]1Haematologica,2010,95:232-2401[9]CortesJE,JonesD,O'BrienS,etal1Nilotinibasfrontlinetreatmentforpatientswithchronicmyeloidleukemiainearlychronicphase[J]1JClinOncol,2010,28:392-3971[10]CortesJE,JonesD,O'BrienS,etal1ResultsofdasatinibtherapyinpatienswithEarlychronic-phasechronicmyeloidleukemia[J]1JClinOncol,2010,28:。

6、398-4041[11]BaccaraniM,CortesJ,PaneF,etal1Chronicmyeloidleukemia:anupdateofconceptsandmanagementrecommendationsofEuro-peanLeukemiaNet[J]1JCinOncol,2009,27:6041-60511[12],1[M]1:,2005:1161[13]LucasCM,WangL,AustinGM,etal1Apopulationstufyofimatinibinchronicmyeloidleukemiademonstrateslowerefficacythaninclinicaltrials[J]1Leukemia,2008,22:1963-19661[14],1[J]1,2008,5(29):285-2881[15]RostiG,PalandriF,CastagnettiF,etal1NilotinibforthefrontlineofPh(+)chronicmyeloidleukemia[J]1Blood,2009,114:4933-49381[16]S。

7、lupianekA,NowickiMO,KoptyraM,etal1BCR/ABLmodifiesthekineticsandfidelityofDNAdouble-strandbreaksrepairinhematopoieticcells[J]1DNARepair,2006,5:243-2501[17]McWeeneySK,PembertonLC,LoriauxMM,etal1AgeneexpressionsignatureofCD34+cellstopredictmajorcytogeneticresponseinchronic-phasechronicmyeloidleukemiapatientstreatedwithimatinib[J]1Blood,2010,115:315-3251[18]HughesT,SaglioG,BranfordS,etal1ImpactofbaselineBCR-ABLmutationsonresponsetonilotinibinpatientswithchronicmye-loidleukemiainchronicphase[J]1JClin。

8、Oncol,2009,27:4204-42101[19]MullerMC,CortesJE,KimDW,etal1Dasatinibtreatmentofchronic-phasechronicmyeloidleukemia:analysisofresponsesaccordingtopreexistingBCR-ABLmutations[J]1Blood,2009,114:4944-49531[20]OehlerVG,YeungKY,ChoiYE,etal1Thederivationofdiagnosticmarkersofchronicmyeloidleukemiaprogressionfrommicroarraydata[J]1Blood,2009,114:3292-32981[21]RadichJP,DaiH,MaoM,etal1Geneexpressionchangesassociatedwithprogressionandresponseinchronicmyeloidleukemia[J]1ProcNatlAcadSciUSA,2006,103:2794-27991[22。

9、]WhiteDL,DangP,EnglerJ,etal1FunctionalactivityoftheOCT-1proteinispredictiveoflong-termoutcomeinpatientswithchro-nic-phasechronicmyeloidleukemiatreatedwithimatinib[J]1JClinOncol,2010,28:2761-27671[23]HughesT,BranfordS1MolecularmonitoringofBCR-ABLasaguidetoclinicalmanagementinchronicmyeloidleukemia[J]1BloodRev,2006,20:29-411[24]MilojkovicD,NicholsonE,ApperleyJF,etal1Earlypredictionofsuccessorfailureoftreatmentwithsecond-generationtyrosinekinaseinhibitorsinpatientswithchronicmyeloidleukemia[J]1Haem。

10、atologica,2010,95:224-2311[25]BranfordS,MeloJV,HughesTP1Selectingoptimalsecond-linetyrosinekinaseinhibitortherapyforchronicmyeloidleukemiapatientsafterimatinibfailure:doestheBCR-ABLmutationstatusreallymatter[J]?Blood,2009,114:5426-54351[26]GrewalSS,BarkerJN,DaviesSM,etal1Unrelateddonorhematopoieticcelltransplantation:marroworumbilicalcordblood[J]?Blood,2008,101:42331[27]FaradSS,FehnigerT,RuggeriL,etal1Naturalkillercellreceptors:newbiologyandinsightsintograftversusleukemiaeffect[J]1Blood。