內(nèi)科學(xué)-白血病-謝毅-課件

2024/4/2ppt課件1

Leukemia(白血病)2024/4/1ppt課件1Leukemia(白血病)12024/4/2ppt課件2ConceptofleukemiaDefinitionLeukemiaisamalignantblooddisorder(notsolidtumor),whichistheresultsofthetumorproliferationofheamotopoieticstemcells.（造血干細(xì)胞）

2024/4/1ppt課件2Conceptofleuke2精品資料精品資料3你怎么稱呼老師？如果老師最后沒有總結(jié)一節(jié)課的重點(diǎn)的難點(diǎn)，你是否會(huì)認(rèn)為老師的教學(xué)方法需要改進(jìn)？你所經(jīng)歷的課堂，是講座式還是討論式？教師的教鞭“不怕太陽曬，也不怕那風(fēng)雨狂，只怕先生罵我笨，沒有學(xué)問無顏見爹娘……”“太陽當(dāng)空照，花兒對(duì)我笑，小鳥說早早早……”內(nèi)科學(xué)-白血病-謝毅-PPT課件42024/4/2ppt課件52024/4/1ppt課件552024/4/2ppt課件6HematopoieticStemCell(HSC)

istheprimarycellofhematopoieticandimmunesystem2024/4/1ppt課件6HematopoieticSt62024/4/2ppt課件7TumorproliferationofHSC

Proliferationisoutofcontrolandapoptosisisinhibited.Leukemiacellisclonedandaccumulatedinagreatquantity,thenormalhemapoiesisisihibited.DifferentiationofHSCisblocked.LeukemiacellsarestoppedonadifferentiationstageofHSC&lackofthenormalfunction.infiltrationandmetastasis2024/4/1ppt課件7Tumorproliferat72024/4/2ppt課件8malignantblooddisorderspathophysiologyClinicalmanifestationHSCdifferentiationisblockedNormalbloodcellsaredecreasedThefunctionofBloodandimmunesystemareshortof.Anemia,fever,hemorrhageAbnormalmorphologypicturesofbloodandbonemarrow.

Proliferationisoutofcontrol,apoptosisisinhibited.Leukemiacellisaccumulatedinagreatquantity.LeukocytesandLeukostasis(白細(xì)胞淤滯)Liver,spleen,lymphnods,skin,CNSetc.areinfiltratedanddysfunctionalfrequently.2024/4/1ppt課件8malignantblood82024/4/2ppt課件9Accordingtothe

acutemyeloidleukemia（AML）Differentiation& M0M1M2………………..M7KindofcellblastcrisisofCML，mastcellleukemia，

acuteeosinophilicleukemia，basophilic…………leukemiaacutelymphocyteleukemia（ALL）

L1，L2，L3T－ALL、B－ALL

chronic

leukemia：CML、P－LL、CLL、HCL、……

leukemia

the

traditionclassification(FAB)ofleukemia2024/4/1ppt課件9Accordingtothe92024/4/2ppt課件10WHOclassification(2001)1,Acutemyeloidleukemia(AML)(1),AMLwithrecurrentcytogeneticabnormalitiesAMLwitht(8;21)(q22;q22),AML1/ETOAMLwitht(15;17)(q22;q12),PML/RAR

AMLwithinv(16)(p13;q22)ort(16;16)(p13;q22),CBF

/MYH11AMLwith11q23(MLL)abnormalities(2),AMLwith,MultilineagedysplasiaWithoutpriormyelodysplasticsyndromeWithpriormyelodysplasticsyndrome(3),AMLandmyelodysplasticsyndrome,therapyrelatedAlkylatingagentrelatedTopoisomerasellinhibitor-related2024/4/1ppt課件10WHOclassificat102024/4/2ppt課件11

WHOclassification(2001)

1,Acutemyeloidleukemia(AML)(4)

AMLnototherwisecategorizedAMLminimallydifferentiationAMLwithoutmaturationAMLwithmaturationAcutemyelomonocyticleukemiaAcutemonoblasticandmonocyticleukemiaAcuteerythroidleukemiaAcutemegakaryoblasticleukemiaAcutebasophilicleukemiaAcutepanmyelosiswithmyelofibrosisMyeloidsarcoma(5)Acuteleukemiaofambiguouslineage2024/4/1ppt課件11WHOclassific112024/4/2ppt課件12WHOclassification(2001)

2,chronicmyeloidleukemia(1),chronicmyeloproliferativedisease(CMPD)chronicmyelogenousleukemia(cmL)ChronicneutrophilicleukemiaChroniceosinophilicleukemia/hypereosinophilicsyndrome(2),myelodysplastic/myeloprolife-rativedisease(MDS/MPD)ChronicmyelomonocyticleukemiaAtypicalchronicmyeloidleukemiaJuvenilemyelomonocyticleukemia2024/4/1ppt課件12WHOclassificat122024/4/2ppt課件13WHOclassification(2001)

3,Lymphoidneoplasms(1),PrecursorB-cellneoplasm

PrecursorBlymphoblasticleukemia(2),MatureB-cellneoplasm

Chroniclymphocyticleukemia/Smalllymphocyticlymphoma(CLL/SLL)B-cellprolymphocyticleukemiaHairycellleukemiaBurkittlymphoma/leukemia(1),PrecursorT-cellneoplasm

PrecursorTlymphoblasticleukemia(2),MatureT-cellandNK-cellneoplasmsT-cellprolymphocyticleukemiaT-celllargegranularlymphocyticleukemiaAggressiveNKleukemia/lymphomaAdultT-cellleukemia/lymphoma2024/4/1ppt課件13WHOclassificat132024/4/2ppt課件14Epidemiology:incidence3/105

，increasewithyears?acute>chronic,AML>ALLSpecialdistribution:Sexman：female＝2：1AgeALL,adolescent80％<20y;AML,adultCML,20~50yearsold;CLL,50~70yearsoldAreaadultTlymphocyticleukemiaCML,easterncountriesCLL,westerncountries2024/4/1ppt課件14Epidemiology:142024/4/2ppt課件15Epidemiology:

mortality2.51/105Areacity>thecountrysideChina<Singapore<Japan<USA<unitedKingdom<Sweden(7.5～9/105)Inorderofthemortalityofmalignanttumorsin1～14y，leukemiaismosthighin15～44y，leukemiaisthirdhigh(<stomachCa<liverCa)inallperson,leukemiaissixthoreighthhigh2024/4/1ppt課件15Epidemiology:m152024/4/2ppt課件16Etiologyradiation1、atombomb1Km1.5km2km

（長(zhǎng)崎）×100×22×2.62、highdoseXradiotherapy、32PtherapyChemicals

benzenchemotherapy-relatedleukemia(47/440000)2024/4/1ppt課件16Etiologyradiat162024/4/2ppt課件17

virusATLV

1981，Japan(鹿兒島)

electricmicroscope：virusCTheserumantibodytiterofATLVdecreasewiththedistancefrom鹿兒島Genetics

twin(sameegg)0.2~0.25sibling10/105Down‘ssyndrome(21+)40－60/105

Fanconianemia4/66Etiology2024/4/1ppt課件17virusATLV19172024/4/2ppt課件18

fromotherblooddisordersMyeloproliferativeDisease(MPD)

chronicmyeloidleukemia(CML)polycythemiavera(PV)primarythrombocythemia(PT)myelofibrosis(MF)

myelodysplasticsyndrome(MDS)paroxysmalnocturnalhemoglobinuria(PNH)lymphomaormyelomaEtiology2024/4/1ppt課件18

fromother182024/4/2ppt課件19MechanismRadiation,chemicals,virus,genetics&otherblooddisordersChromosometranslocation

FusiongeneformationFusionprotein（enzyme……）

MalignantbiologicbehaviorsMalignantblooddisorders2024/4/1ppt課件19MechanismRadiat192024/4/2ppt課件201,fever,bleeding,anemiaWBC↓→immune↓(～AIDS)→feverTheplacewhereskinandmucosameet:respiratorytube,mouth,perineum,anusInflammatoryreactionisweakG－B(psuedomonasaeruginosa……),interstitialpneumonia(peumocystiscarinii,CMV，herpesvirus),candidaPLT↓

bleeding

skin,mucosaorcranialcavityRBC↓

anemiaAcuteleukemiaClinicalManifestation2024/4/1ppt課件201,fever,bleed202024/4/2ppt課件21AcuteleukemiaClinicalManifestation2、infiltration

Lymphadenopathy,maybenottender;splenomegalyandhepatomegaly,sternaltendernessSpecialinfiltrationareaChloromas:skin,orbit(granulocyticsarcoma)Painlessenlargementoftesticle(ALL)CNSinvolvement,paraplegia(ALL,M4,M5)gingivitis(M4,M5)

2024/4/1ppt課件21Acuteleukemia212024/4/2ppt課件22AcuteleukemiaClinicalManifestation3、AbnormalmorphologypicturesofbloodandbonemarrowBlood：WBCfrom<1×109/L(nonleukemoid)to>100×109/L(hyperleukocytosis),blastsarepresent,anemia,PLT↓BM：proliferative(orhypoplastic)，blasts>20%,Auer‘srods(+),erythropoiesis↓，megakaryocytopoiesis↓2024/4/1ppt課件22Acuteleukemia222024/4/2ppt課件23Normalbonemarrowcell2024/4/1ppt課件23Normalbonemar232024/4/2ppt課件24leukemiacells(showAuer’srods)2024/4/1ppt課件24leukemiacells242024/4/2ppt課件25Clinic

DiagnosisofALThebloodcell↓andluekemiacell↑areshownbyclinicalsigns,symptomsandthefeaturesoflaboratoryandimagingexaminations.blastmorethan20%innonerythrocyticcells(NEC)ofbonemarrowsmearMICMTYPINGDIAGNOSISMorphology,Immunology,Cytogenetics,Molecular2024/4/1ppt課件25ClinicDiagnosi252024/4/2ppt課件26morphology

lymphoblastmyeloblastmonoblastplasma少，透明中，Auer‘s多，泡沫樣chromatin粗粒細(xì)砂 細(xì)chromosome短粗細(xì)長(zhǎng)

粗 Accompany破碎C,幼淋粒系幼單,成熟單POX － ＋/＋＋粗粒－/＋細(xì)粒NSE － －/+,NaF不抑制＋,NaF抑制PAS 粗粒－結(jié)塊彌漫一片紅鐘表面樣2024/4/1ppt課件26morphology262024/4/2ppt課件27IMMUNO-PHENOTYPING

mab M1 M2 M3 M4 M5 M6 M7CD13 + + + + + - -CD33 + + + + + - -CD14 - ± - + + - -CD41 - - - - - - +Ret - - - - - + -Lectoferrin- + - + - - - CD19 CD7 HLA-DR CD3 MPO T - + - + - B + - + - -2024/4/1ppt課件27IMMUNO-PHENOTYP272024/4/2ppt課件28

ChromosometranslocationFusiongeneM2t(8;21)AML1/ETOM3

t(15;17)PML/RAR

M4inv(16),t(16;16)CBF

/MYH11M5t(4;11),11q23MLLabnormalitesALL(15%)L3t(9;22)t(8;14)BCR/ABLMYC,IgHrearrangement2024/4/1ppt課件28Chromosome282024/4/2ppt課件29DifferentialDiagnosisofALMyelodysplasticsyndrome(MDS)

refractoryanemiaorpancytopenia,BM:dysplasiaandblasts<20%Leukemoidreaction

matureleukocytesproliferativewouldplayamainrole,NAP↑,ifprogenitorincrease,onlyshortlyontimeCML:matureprogenitors↑

E↑、B↑，NAP=0,ph'(＋)，bcr-abl(+)Stomatitis，Infectiousmononucleosis，ITP,AA，agranulocytopenia

Thereisnoblastsinbonemarrow2024/4/1ppt課件29DifferentialDi292024/4/2ppt課件30TherapeuticprincipleofAL:early，combine，full，interval，bystageswhyearly?Thehyperplasia&infiltrationcouldbringthedifficultyontherapyTumorlysisLeukemiacellenterintotheareaprotectedbythebarrierbetweenbloodandbrain

2024/4/1ppt課件30Therapeuticpri302024/4/2ppt課件31TherapeuticprincipleofAL:early，combine，full，interval，bystagescombinationregimenofthesedrugswhichhave

differenttyping,actionandtoxicityareused

Toincreasecurativeeffectanddecreasetoxicityanti-infection,supportandchemotherapytobedoneatsametimeifitwerenecessary

2024/4/1ppt課件31Therapeuticpri312024/4/2ppt課件32Cellcycleandchemotherapy

Go(sourceofrelapse) endcell apoptosis(differentiation)

sensitiveinsensitiveG1SG2M2024/4/1ppt課件32Cellcycleand322024/4/2ppt課件33Thedrugtyping

CCSA CCNSAAntimetabolicdrugs alkylatingdrugsS,6MP,6TG,Ara-C,CC,mustine，CTX，BU,CB1348MTX,HUm-CCNUS/G2VP16,VM26 anthracyclineantibiotics

MVCR,VDSbleomycinA5(平陽霉素)G1G2,L-ASP,prednisoneharringtonine(三尖杉)

theeffectisincreasedbytimetheeffectincreasedbydosage2024/4/1ppt課件33Thedrugtyping332024/4/2ppt課件34DifferentActionofDrugs嘌呤堿嘧啶堿

6MP6TGMTX 氮雜胞苷核苷酸

MTXHU

脫氧核苷酸

VM26 Ara-C,CC

蒽環(huán)類抗生素DNA破壞烷化劑，CCNUAMSARNADNAL－ASPVCR,VM26protein子細(xì)胞DNA蒽環(huán)類：阿霉素，表阿霉素，柔紅，阿克拉，米妥蒽醌烷化劑：CTX，氮芥，BU，CB1348，CCNU，BCNUVP162024/4/1ppt課件34DifferentActi342024/4/2ppt課件35Thetoxicityofthedrugs

烷化劑 抗代謝類VCR三尖杉激素蒽環(huán)類BM抑制 ＋＋＋ ＋＋＋－＋＋－＋＋＋脫發(fā)＋＋ ＋ ＋＋＋口腔潰瘍 ＋＋＋

胃腸反應(yīng) ＋＋＋＋＋ ＋＋＋周圍N炎 ＋＋＋

心毒 ＋＋

＋＋＋免疫抑制＋＋＋＋＋＋＋＋＋＋＋＋＋＋誘變畸變 √ √ √√√√出血性膀胱炎＋＋＋

肝毒 ＋ ＋ ＋＋＋2024/4/1ppt課件35Thetoxicityof352024/4/2ppt課件36TherapeuticprincipleofAL:early，combine，full，interval，bystagesfull

thedosageshouldbefullthedrugshouldworkinallperiodofcellcycleKillingthecellsinallperiodofcellcycleTheregimenwouldbeusedrepeatedlyrepeatedlycouldmakeG0→cycle&controlthesourceofrelapse（MRD)

2024/4/1ppt課件36Therapeuticpri362024/4/2ppt課件37TherapeuticprincipleofAL:early，combine，full，interval，bystagesIntervalfor3~4weeksbeforenexttherapy

Leukemiacellnormalcell

Whengetdisease

thegreaterpartofcellstheproliferationis

isnotinG0period

inhibited

easilykilledbychemotherapyinG0perioddoublingtime

longshortRecoverinintervalnoteasytorecovereasytorecover

2024/4/1ppt課件37Therapeuticpri372024/4/2ppt課件38TherapeuticprincipleofAL:early，combine，full，interval，bystages

inductionconsolidationmaintenanceofCR6cycles3～5years?1011～1013106～8104（MRD）

preventCNSleukemia

ToreduceMRDstepbystep,keeptheDFSforlongtimeCR:therearenotanemia,fever,hemorrhageandinfiltrationHb>100g/L,WBC<10×109/L,PLT>100×109/BM,blasts<5%2024/4/1ppt課件38Therapeuticpri382024/4/2ppt課件39（1）Regimen

induced

remissionforALLVP (classical) VCR1～2mg+NS20ccVqw Prednisone20~30mg/dp.o useittillCR,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.2024/4/1ppt課件39（1）Regimenind392024/4/2ppt課件40（2）Regimen

induced

remissionforANLLHOAP(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%2024/4/1ppt課件40（2）Regimenin402024/4/2ppt課件41

（3）Regimen

induced

remissionforALPML(M3):retinoidacid(ATRA)60－80mgp.oMayaddAs2O35mgVgtt×28dUsechemotherapyinconsolidationstageUsethelowmolecularheparinwhenwithDICHypoplasticleukemia:CAG/CHGAra-C12.5mgMqd×21d,G-CSF300

gMqd×21dharringtonine1mgM/aclarubicin10mgVqd×21dHyperplasticleukemia(WBC>100×109/L)TherapeuticLeukapheresistotreattheLeukostasisTopreventtumorlysissyndromeImmunotherapy:CD33

monoantibody+drug2024/4/1ppt課件41（3）Regimenin412024/4/2ppt課件42

(4)supportivecareforALantibiotics（倒階梯）,IVIG,rhG-CSFconponenttransfusiontherapyRBC,rhEPOplateletVeinhighnutritionprotectheart,liver&kidney2024/4/1ppt課件42(4)support422024/4/2ppt課件43Theregimen

inconsolidationremissionstageUsingdifferentinductionremissionregimenalternatelyforsixcyclesHemapoieticstemcelltransplantation

M3inCR2CouldbecurableExpensiveandhighrisk2024/4/1ppt課件43Theregimen

in432024/4/2ppt課件44

theregimen

inmaintenanceremissionstageNotmaintaintherapyforAMLunlessleukemiarelapse.Protectthecapacityofbodyimmunityimprovequalityoflife

TotreatALLwithoutHSCTintervaltimewillbeextendedusingthedifferentinductionremissionregimenalternatelyfor3~5YwilltakeCTX，6-MP，6-TG&MTX,P.Oinintervaltime2024/4/1ppt課件44

theregimen

i442024/4/2ppt課件45

CNSleukemiaIncidence:ALL10－40%，ANLL2－4%Couldbefoundinyouthage，whosufferedfrominfiltration,easilyonsetinremissionstagealways

ClinicalexaminationIntracranialhypertensionThesignsofmeningesstimulatedthesignsofnervesinjureCSFexaminationpresure>200mmH20,sugar

，protein（>40mg/dl),WBC>10/mm3couldfindleukemiacells2024/4/1ppt課件45CNSleukemi452024/4/2ppt課件46

ThetreatmentofCNSleukemia

ThepreventionofCNSleukemiaAfterCR,MTX5－10mgsheathrejectionqw×6IncidenceofCNSleukemia

,<5%ThetreatmentofCNSleukemiaHighdoseMTXinjectionMTX5－10mgsheathenjectionBiw－qw(dilutionwithinjectionwater3ml,adddexamethasome5mg)2.4Gy60Coradiationtohead2024/4/1ppt課件46Thetreatmen462024/4/2ppt課件47ChronicMyelogenousLeukemia(CML)

aClonalproliferativedisorderofpluripotentstemcellAbout15~25%ofallcasesofleukemiaAges25~60years,slightlymore