内科学 白血病-谢毅.ppt

2020 2 5 xieYi HuaShanHospital 1 Leukemia 白血病 谢毅 Xieyi Dep Hematology HuashanHospitalFuDanUniversity 2020 2 5 xieYi HuaShanHospital 2 Conceptofleukemia DefinitionLeukemiaisamalignantblooddisorder notsolidtumor whichistheresultsofthetumorproliferationofheamotopoieticstemcells 造血干细胞 2020 2 5 xieYi HuaShanHospital 3 2020 2 5 xieYi HuaShanHospital 4 HematopoieticStemCell HSC istheprimarycellofhematopoieticandimmunesystem 2020 2 5 xieYi HuaShanHospital 5 TumorproliferationofHSC Proliferationisoutofcontrolandapoptosisisinhibited Leukemiacellisclonedandaccumulatedinagreatquantity thenormalhemapoiesisisihibited DifferentiationofHSCisblocked LeukemiacellsarestoppedonadifferentiationstageofHSC lackofthenormalfunction infiltrationandmetastasis 2020 2 5 xieYi HuaShanHospital 6 malignantblooddisorders 2020 2 5 xieYi HuaShanHospital 7 Accordingtotheacutemyeloidleukemia AML Differentiation M0M1M2 M7KindofcellblastcrisisofCML mastcellleukemia acuteeosinophilicleukemia basophilic leukemiaacutelymphocyteleukemia ALL L1 L2 L3T ALL B ALLchronicleukemia CML P LL CLL HCL leukemia thetraditionclassification FAB ofleukemia 2020 2 5 xieYi HuaShanHospital 8 WHOclassification 2001 1 Acutemyeloidleukemia AML 2020 2 5 xieYi HuaShanHospital 9 WHOclassification 2001 1 Acutemyeloidleukemia AML 2020 2 5 xieYi HuaShanHospital 10 WHOclassification 2001 2 chronicmyeloidleukemia 2020 2 5 xieYi HuaShanHospital 11 WHOclassification 2001 3 Lymphoidneoplasms 2020 2 5 xieYi HuaShanHospital 12 Epidemiology incidence 3 105 increasewithyears acute chronic AML ALLSpecialdistribution Sexman female 2 1AgeALL adolescent80 20y AML adultCML 20 50yearsold CLL 50 70yearsoldAreaadultTlymphocyticleukemiaCML easterncountriesCLL westerncountries 2020 2 5 xieYi HuaShanHospital 13 Epidemiology mortality 2 51 105Areacity thecountrysideChina Singapore Japan USA unitedKingdom Sweden 7 5 9 105 Inorderofthemortalityofmalignanttumorsin1 14y leukemiaismosthighin15 44y leukemiaisthirdhigh stomachCa liverCa inallperson leukemiaissixthoreighthhigh 2020 2 5 xieYi HuaShanHospital 14 Etiology radiation1 atombomb1Km1 5km2km 长崎 100 22 2 62 highdoseXradiotherapy 32PtherapyChemicalsbenzenchemotherapy relatedleukemia 47 440000 2020 2 5 xieYi HuaShanHospital 15 virusATLV1981 Japan 鹿儿岛 electricmicroscope virusCTheserumantibodytiterofATLVdecreasewiththedistancefrom鹿儿岛Geneticstwin sameegg 0 2 0 25sibling10 105Down ssyndrome 21 40 60 105Fanconianemia4 66 Etiology 2020 2 5 xieYi HuaShanHospital 16 fromotherblooddisordersMyeloproliferativeDisease MPD chronicmyeloidleukemia CML polycythemiavera PV primarythrombocythemia PT myelofibrosis MF myelodysplasticsyndrome MDS paroxysmalnocturnalhemoglobinuria PNH lymphomaormyeloma Etiology 2020 2 5 xieYi HuaShanHospital 17 Mechanism Radiation chemicals virus genetics otherblooddisordersChromosometranslocationFusiongeneformationFusionprotein enzyme MalignantbiologicbehaviorsMalignantblooddisorders 2020 2 5 xieYi HuaShanHospital 18 1 fever bleeding anemiaWBC immune AIDS feverTheplacewhereskinandmucosameet respiratorytube mouth perineum anusInflammatoryreactionisweakG B psuedomonasaeruginosa interstitialpneumonia peumocystiscarinii CMV herpesvirus candidaPLT bleedingskin mucosaorcranialcavityRBC anemia AcuteleukemiaClinicalManifestation 2020 2 5 xieYi HuaShanHospital 19 AcuteleukemiaClinicalManifestation 2 infiltrationLymphadenopathy maybenottender splenomegalyandhepatomegaly sternaltendernessSpecialinfiltrationareaChloromas skin orbit granulocyticsarcoma Painlessenlargementoftesticle ALL CNSinvolvement paraplegia ALL M4 M5 gingivitis M4 M5 2020 2 5 xieYi HuaShanHospital 20 AcuteleukemiaClinicalManifestation 3 AbnormalmorphologypicturesofbloodandbonemarrowBlood WBCfrom100 109 L hyperleukocytosis blastsarepresent anemia PLT BM proliferative orhypoplastic blasts 20 Auer srods erythropoiesis megakaryocytopoiesis Normalbonemarrowcell leukemiacells showAuer srods 2020 2 5 xieYi HuaShanHospital 23 ClinicDiagnosisofAL Thebloodcell andluekemiacell areshownbyclinicalsigns symptomsandthefeaturesoflaboratoryandimagingexaminations blastmorethan20 innonerythrocyticcells NEC ofbonemarrowsmearMICMTYPINGDIAGNOSISMorphology Immunology Cytogenetics Molecular morphology IMMUNO PHENOTYPING mabM1M2M3M4M5M6M7CD13 CD33 CD14 CD41 Ret Lectoferrin CD19CD7HLA DRCD3MPOT B 2020 2 5 xieYi HuaShanHospital 27 DifferentialDiagnosisofAL Myelodysplasticsyndrome MDS refractoryanemiaorpancytopenia BM dysplasiaandblasts 20 Leukemoidreactionmatureleukocytesproliferativewouldplayamainrole NAP ifprogenitorincrease onlyshortlyontimeCML matureprogenitors E B NAP 0 ph bcr abl Stomatitis Infectiousmononucleosis ITP AA agranulocytopeniaThereisnoblastsinbonemarrow TherapeuticprincipleofAL early combine full interval bystages whyearly Thehyperplasia infiltrationcouldbringthedifficultyontherapyTumorlysisLeukemiacellenterintotheareaprotectedbythebarrierbetweenbloodandbrain TherapeuticprincipleofAL early combine full interval bystages combinationregimenofthesedrugswhichhavedifferenttyping actionandtoxicityareusedToincreasecurativeeffectanddecreasetoxicityanti infection supportandchemotherapytobedoneatsametimeifitwerenecessary Cellcycleandchemotherapy Go sourceofrelapse endcellapoptosis differentiation sensitiveinsensitive G1 S G2 M 2020 2 5 xieYi HuaShanHospital 31 Thedrugtyping CCSACCNSAAntimetabolicdrugsalkylatingdrugsS 6MP 6TG Ara C CC mustine CTX BU CB1348MTX HUm CCNUS G2VP16 VM26anthracyclineantibioticsMVCR VDSbleomycinA5 平阳霉素 G1G2 L ASP prednisoneharringtonine 三尖杉 theeffectisincreasedbytimetheeffectincreasedbydosage 2020 2 5 xieYi HuaShanHospital 32 DifferentActionofDrugs 嘌呤碱嘧啶碱6MP6TGMTX氮杂胞苷核苷酸MTXHU脱氧核苷酸VM26Ara C CC蒽环类抗生素DNA破坏烷化剂 CCNUAMSARNADNAL ASPVCR VM26protein子细胞DNA蒽环类 阿霉素 表阿霉素 柔红 阿克拉 米妥蒽醌烷化剂 CTX 氮芥 BU CB1348 CCNU BCNU VP16 2020 2 5 xieYi HuaShanHospital 33 Thetoxicityofthedrugs 烷化剂抗代谢类VCR三尖杉激素蒽环类BM抑制 脱发 口腔溃疡 胃肠反应 周围N炎 心毒 免疫抑制 诱变畸变 出血性膀胱炎 肝毒 2020 2 5 xieYi HuaShanHospital 34 TherapeuticprincipleofAL early combine full interval bystages fullthedosageshouldbefullthedrugshouldworkinallperiodofcellcycleKillingthecellsinallperiodofcellcycleTheregimenwouldbeusedrepeatedlyrepeatedlycouldmakeG0 cycle controlthesourceofrelapse MRD 2020 2 5 xieYi HuaShanHospital 35 TherapeuticprincipleofAL early combine full interval bystages Intervalfor3 4weeksbeforenexttherapyLeukemiacellnormalcellWhengetdiseasethegreaterpartofcellstheproliferationisisnotinG0periodinhibitedeasilykilledbychemotherapyinG0perioddoublingtimelongshortRecoverinintervalnoteasytorecovereasytorecover 2020 2 5 xieYi HuaShanHospital 36 TherapeuticprincipleofAL early combine full interval bystages inductionconsolidationmaintenanceofCR6cycles3 5years 1011 1013106 8104 MRD preventCNSleukemia ToreduceMRDstepbystep keeptheDFSforlongtime CR therearenotanemia fever hemorrhageandinfiltrationHb 100g L WBC100 109 BM blasts 5 2020 2 5 xieYi HuaShanHospital 37 1 RegimeninducedremissionforALL VP classical VCR1 2mg NS20ccVqwPrednisone20 30mg dp ouseittillCR CR50 butrelapseeasilyVDLPVCR1 2mg NS20ccVqw 1 8 15 21d DNR30 40mgVgttqd1 3d 15 17dPred40mg 60mgp o1 14dL ASP10 000uVgtt19 28dCR72 77 VP160 2Vgttqd 3dAra C0 1 0 15Vgttqd 7dMTX2 3gVgtt24h after12h leucovorin6 9mgmq8h 2dhydrotherapy alkalizeItcouldbeusedinCNSleukemia 2020 2 5 xieYi HuaShanHospital 38 2 RegimeninducedremissionforANLL HOAP classical VCR1 2mgV1dharringtonine1 4mgVgttqd 5 7d interval14d Ara C50 100mgVgttBid 5 7dPrednisone30 60mgp oqd 5 7dHAharringtonine2 4mgVgtt 7Ara C0 1 0 2Vgtt 7HDAra CAra C2 0Vgttq12h 3DADNR30 40mgVgtt 3Ara C0 1 0 2Vgtt 7CR65 85 2020 2 5 xieYi HuaShanHospital 39 3 RegimeninducedremissionforAL PML M3 retinoidacid ATRA 60 80mgp oMayaddAs2O35mgVgtt 28dUsechemotherapyinconsolidationstageUsethelowmolecularheparinwhenwithDICHypoplasticleukemia CAG CHGAra C12 5mgMqd 21d G CSF300 gMqd 21dharringtonine1mgM aclarubicin10mgVqd 21dHyperplasticleukemia WBC 100 109 L TherapeuticLeukapheresistotreattheLeukostasisTopreventtumorlysissyndromeImmunotherapy CD33monoantibody drug 2020 2 5 xieYi HuaShanHospital 40 4 supportivecareforAL antibiotics 倒阶梯 IVIG rhG CSFconponenttransfusiontherapyRBC rhEPOplateletVeinhighnutritionprotectheart liver kidney 2020 2 5 xieYi HuaShanHospital 41 Theregimeninconsolidationremissionstage UsingdifferentinductionremissionregimenalternatelyforsixcyclesHemapoieticstemcelltransplantationM3inCR2CouldbecurableExpensiveandhighrisk 2020 2 5 xieYi HuaShanHospital 42 theregimeninmaintenanceremissionstage NotmaintaintherapyforAMLunlessleukemiarelapse ProtectthecapacityofbodyimmunityimprovequalityoflifeTotreatALLwithoutHSCTintervaltimewillbeextendedusingthedifferentinductionremissionregimenalternatelyfor3 5YwilltakeCTX 6 MP 6 TG MTX P Oinintervaltime 2020 2 5 xieYi HuaShanHospital 43 CNSleukemia Incidence ALL10 40 ANLL2 4 Couldbefoundinyouthage whosufferedfrominfiltration easilyonsetinremissionstagealwaysClinicalexaminationIntracranialhypertensionThesignsofmeningesstimulatedthesignsofnervesinjureCSFexaminationpresure 200mmH20 sugar protein 40mg dl WBC 10 mm3couldfindleukemiacells 2020 2 5 xieYi HuaShanHospital 44 ThetreatmentofCNSleukemia ThepreventionofCNSleukemiaAfterCR MTX5 10mgsheathrejectionqw 6IncidenceofCNSleukemia 5 ThetreatmentofCNSleukemiaHighdoseMTXinjectionMTX5 10mgsheathenjectionBiw qw dilutionwithinjectionwater3ml adddexamethasome5mg 2 4Gy60Coradiationtohead 2020 2 5 xieYi HuaShanHospital 45 ChronicMyelogenousLeukemia CML aClonalproliferativedisorderofpluripotentstemcellAbout15 25 ofallcasesofleukemiaAges25 60years slightlymoreinmenthanwomenConsistentlyassociatedwiththePhchromosomeandBCR ABLfusiongeneInitialindolentchro