白血病幻灯片

Leukemia（白血病）

陈方平白血病Leukemia

TherapyandPrognonisContentsOutlineClassificationClinicalfeaturesDiagnosisAcuteleukemaChronicleukema白血病WhatIsLeukemia?CancerofthewhitebloodcellsAcuteorChronicAffectsabilitytoproducenormalbloodcellsBonemarrowmakesabnormallylargenumberofimmaturewhitebloodcellscalledblasts白血病Definition

AbnormalityofWBCMarrowfailureInfiltrationoftissues

HematopoieticstemcellmalignanciesMalignantproliferationofleukemiccells白血病DevelopmentofLeukemiaintheBloodstreamStage1-NormalStage2-SymptomsStage3-DiagnosisStage4-WorseningStage5a-AnemiaStage5b-InfectionLegendWhiteCellRedCellPlateletBlastGermSourcesfromLeukemia,byD.NewtonandD.Siegel白血病HistoryMeans“whiteblood”inGreekDiscoveredbyDr.AlfredVelpeauinFrance,1827NamedbypathologistRudolfVirchowinGermany,1845白血病ResultsinChina（N/100,000）Morbilityinadults2.01.0

ANLL

ALLCMLCLL1.620.690.360.05Morbility白血病EtiologyVirusRadiationChemicalsInheritanceOtherkindsofhematopoieticdisease白血病ClassificationofleukemiaAcuteChronicMyeloidoriginLymphoidoriginAcuteMyeloidLeukemia(AML)AcuteLymphoblasticLeukemia(ALL)ChronicMyeloidLeukemia(CML)ChronicLymphocyticLeukemia(CLL)白血病HematopoieticStemCellLifespanDecadesYearsMonthsWeeks,DaysRedbloodcellsWhitebloodcellsPlatelets白血病LifespanDecadesYearsMonthsWeeks,DaysRedbloodcellsWhitebloodcellsPlateletsHematopoieticStemCell白血病RedbloodcellsWhitebloodcellsPlateletsHematopoieticStemCell白血病RedbloodcellsWhitebloodcellsPlateletsHematopoieticStemCell白血病AcuteLeukemiaHematopoieticStemCell白血病HematopoieticStemCellChemotherapy白血病HematopoieticStemCellRedbloodcellsWhitebloodcellsPlateletsRemissionResidualleukemiastemcells白血病HematopoieticstemcellNeutrophilsEosinophilsBasophilsMonocytesPlateletsRedcellsMyeloidprogenitorLymphoidprogenitorB-lymphocytesT-lymphocytesPlasmacellsgerminalcenternaïveALLAML白血病differentiationblockenhancedproliferationAcuteLeukemia+Gainoffunctionmutationsoftyrosinekinaseseg.FLT3,c-KITmutationsN-andK-RASmutationsBCR-ABLTEL-PDGFbRLossoffunctionoftranscriptionfactorsneededfordifferentiationeg.AML1-ETOCBFb-SMMHCPML-RARaTwo-hitmodelofleukemogenesis白血病ClassificationofacuteleukemiaALLmainlychildrenM>Fcurablein70%ofchildrencurableinminorityofadultsAMLmainlyadultsM>Fcurableinminorityofadults白血病Clinicalfeatures

(一)MalignantproliferationofleukemiccellsMarrowfailureInfiltrationoftissuesAnemiaFeverBleedingAcuteleukemia白血病Clinicalfeatures

(二)AcuteleukemiaAnemia

(progressive,weakness,pale)Fever(mostlybyinfection)

CommonSevereUncontrolledPathogen：G-、G+、virus、funguset.al白血病Clinicalfeatures

(三)AcuteleukemiaBleeding

Common、progressivelocus：skinandmucous

（purpura、ecchymosis

）

Bleedingofinternalorgans白血病petechiaecchymosispurpura白血病Clinicalfeatures

(三)AcuteleukemiaInfiltrationoftissues/organsLymphnode,enlargementofliverandspleenBonepainCNSL（中枢神经系统白血病）

Mouth、skin、eye（Granulocyticsarcoma

）

Other（testis）白血病Infiltrationoftissues(gum)白血病Infiltrationoftissues(skin)白血病lymphadenopathy白血病Splenomegaly白血病Laboratory(一)Bloodtest

WBC+DC：HyperleukocyticAL(＞100×109/L)

Hypoplastic

AL(lowerthannormal)

Blasticcellandjuvenilecells

HB+RBCPtAcuteleukemia白血病PicturesOfBloodNormalhumanbloodWhiteCellRedCellPlateletBloodwithleukemiaBlastsRedCellPlateletWhiteCell白血病Marrowblasticcells≥30%normalbloodcellsreducedhypoplasticleukemiaAuerrods数的异常质的异常AcuteleukemiaLaboratory(二)白血病Siteformarrowsamples白血病MarrowBiopsy:CellularorHypercellularHypocellular白血病

NormalAML

ALL

Auerrods白血病ClassificationofacuteleukemiaMethods1.FAB2.MICM白血病SubclassificationALL

Commontype(pre-B)B-cellT-cellUndifferentiated白血病ALLL1(85%):smaller,highn/cratio,indistinctnucleoli白血病ALLL2(14%):larger,morecytoplasm,pleomorphic,moredistinctnucleoli白血病ALLL3(1%):cytoplasmicbasophilia(Ig),vacuoles(Burkitt’sleukemia)白血病MyelomonoFABofAML白血病AMLFrench-American-British(FAB)ClassificationM0:MinimallydifferentiatedleukemiaM1:MyeloblasticleukemiawithoutmaturationM2:MyeloblasticleukemiawithmaturationM3:HypergranularpromyelocyticleukemiaM4Eo:Variant:IncreaseinabnormalmarroweosinophilsM4:MyelomonocyticleukemiaM5:MonocyticleukemiaM6:Erythroleukemia(DiGuglielmo'sdisease)M7:Megakaryoblasticleukemia白血病形态学Morphology免疫学

Immunology细胞遗传学Cytogenetics分子生物学MolecularbiologyMICMClassificationofacuteleukemia白血病MPO(right)&Sudanblack(left)showingintenselocalisedpositivityinblasts白血病Laboratory（三）Chemicaldye

L(淋)M（粒）N（单）POX

-++～+++-～+NSE

--～+++～+++NaF

-+

PAS+～++-～++～++Acuteleukemia白血病AcuteleukemiaLaboratory(四)Immunology

ANLL—CD13、CD33、CD14

T-ALL—CD3、CD2、CD7、CD8B-ALL—CD10、CD19、CD22

、HLA-DR

cytogeneticsandmolecularbiology

Ｍ3T(15;17)(q22;q21)PML-RARaL1T(9,22)(q34;q11)BCR-ABL

白血病

AcuteleukemiaMethod：twostepsDifferentialdiagnosisAcuteleukemiawithnormalamountofWBCs

①AA②PNH③ITP④recoveryofleukophenia⑤MDS⑥IDAAcuteleukemiawithhigheramountofWBCs①infectiousmonocytosis②leukemoidreaction

Diagnosis白血病TherapyofAL（一）SupportivemedicalcareControllinginfectionAvoidingbleedingandanemiaHematopoieticCellfactorsProtectionofimportantorgans白血病TherapyofAL（二）ChemotherapyPurpose：

firstgoalisCR，furtherRxtopreventrelapse

CR(completeremission)symptomsandsignsdisappearPB：HB≥100g/lN≥1.5×109/lPt≥100×109/lwithnoleukocyteBMBlastcells≤5%Rules：early,complete,combined

intermittent,differentstage白血病

TherapyofAL（三）Chemotherapy3stagesinduction（初治）→consolidation（巩固强化）→maintenance（维持治疗）leukemiccells1010-13106-8104（symptom）（CR）（maintenance）白血病othersRadiotherapy

OnlyforCNSL、TestisleukemiaandBMTHSCTransplantationGeneTherapy

TherapyofAL（三）白血病Hematopoieticstemcelltransplantationpermits“rescue”fromotherwiseexcessivelytoxictreatmentadditionaladvantageofgraft-vs-leukemiaeffectinallogeneictransplantstrade-offforallogeneictransplantation:greateranti-leukemiceffectbutmoretoxic白血病

Factors

Age、amountofWBCs、MDSFAB、cytogeneticAcuteleukemiaprognosis白血病PrognosisAdultAMLAdultALLsimilartoorworsethanAML白血病ClinicalPresentation:Itcanoccurinanyage.Butthemostagepresentationisbetween40-60.Symptomsrelatedtohypermetabolism:(weightloss,lassitude,anorexiaornightsweats).(Goutorrenalimpairmentcausedbyhyperuriceamia).Bonemarrowfailure:Anemia.白血病CML

Ph+vePh–ve,BCR-abl+vePh–ve,BCR-abl-veEosinophilicLeukemia

Ph:PhiladelphiachromosomeBCR:Breakpointclusterregion;abl:AbelsononcogeneChronicmyeloidleukemia白血病Picture4.Bonemarrowfilmat400Xmagnificationdemonstratescleardominanceofgranulopoiesis.Thenumberofeosinophilsandmegakaryocytesisincreased.白血病Philadelphia:Isthechromosomewhichresultfromthet(9;22)(q34;q11)partoftheAbelsonproto-oncogeneABLismovedtotheBCRgeneonchromosome22&partofchromosome22movestochromosome9.Theabn