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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
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