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第六篇血液系統疾病
第九章白血病(Leukemia)周劍峰學時數:3學時講授目的和要求1.掌握急、慢性白血病的臨床表現,實驗室檢查及診斷標準,治療原則。2.熟悉急性白血病FAB分型,聯合化療的原則,完全緩解的概念。講授主要內容概述病因和發病機制臨床表現實驗室檢查診斷標準鑒別診斷治療概述Erythrocytes:transportoxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefenseagainstinfectionPlatelets:MediatebloodclottingT-lymphocytes:antigenpresentingB-lymphocytesPlasmacell:SourceofantibodiesPluripotentialstemcellsMyeloidstemcellsLymphoidstemcellsUnipotentialprogenitorcellsImmaturehematopoieticcellsmaturehematopoieticcellsHematopoiesiscomposesoftheoptionsofcommitmenttodifferentlineagesandtheprogressivestagesofmaturationatwhichpartialorcompletearrestcanoccur,resultsinthewidearrayofmalignantdisease-Leukemia.StemcellProgenitorcellImmaturecellMaturecellAccumulationofmutationsofDNAwithinapluripotentialstemcellorveryearlyprogenitorcellgivesrisetoleukemicstemcells.NormalstemcellLeukemicstemcell病因和發病機制Etiology&PathogenesisEnvironmentalfactors
AcquireddiseasesLesionstotheDNAClonalexpansionAlotofenvironmentalfactorshasbeenreportedtocauseleukemia.However,onlyfourofthemarefirmlyestablishedcausalagents.Theyare:IrradiationexposureChronicbenzeneexposureChemotherapeuticagentsLeukemiavirusinfectionEnvironmentalfactorscauseleukemiaInheritedsyndromessuchasataxia-telangiectasia,downsyndromepredisposetosubsequentdevelopmentofleukemia.Usually,thesekindsofsyndromessharethecommonfeaturesthattheyallhavehereticdefectsintheirgenomegavebytheirparents.InheritedsyndromespredisposetoleukemiaAcquireddiseasepredisposetoleukemiaLeukemiamayalsodevelopfromtheprogressionofotherclonaldisordersofhematopoieticstemcells.Ploycythemiavera,idiopathicmyelofibrosis,etc.LeukemiaClassificationThereareatleastdozensofvarietiesofleukemia.Theyareclassifiedbyhowquicklyitprogresses.Acuteleukemiaisfast-growingandcanoverrunthebodywithinafewweeksormonths.ByContrast,chronicleukemiaisslow-growingandprogressivelyworsenoveryears.AcuteversuschronicleukemiaAcute:thebloodcellsofacuteleukemiaremaininanimmaturestate,sotheyreproduceandaccumulateveryrapidly.Therefore,theyneedtreatmentimmediately,otherwisethediseasemaybefatalwithinfewmonths.Chronic:inChronicleukemia,thebloodcellseventuallymature,orpartiallymature.Buttheyarenot“normal”.Theyremaininthebloodmuchlongerthannormalbloodcellsandtheycannotactfunctionalcellswell.MyelogenousversuslymphocyticleukemiaIftheleukemiccellsarisefrommyeloidpluripotentialstemcells:myeloidleukemiaIftheleukemiccellsarisefromlymphocyticpluripotentialstemcells:lymphocyticleukemia臨床表現ClinicalmanifestationsLeukemichematopoiesisNormalhematopoiesismarrowfailureInfiltrationMarrowfailureAnemia(lossoferythocytes):fatigues,pallorweakness,reducedexercisetolerance.Feverandinfection(Poorinfectionfighters).Abnormalbleeding(lossofplatelets).InfiltrationsOraltissue:swollenpainful,andbleedinggums.Splenomegalyandhepatomegaly.Lymphnodeenlargement.Boneorjointpain.CNS-headaches,seizures,weakness,blurredvisionandvomiting.實驗室檢查
BloodtestfindingsAnemiaisaconstantfeature.Nucleatedredcellsorimmatureredbloodcellmaybepresent.Thrombocytopeniaisnearlyalwayspresentatthetimeofdiagnosis.Thetotalleukocytecountscanbehigh,normalorlow.
Immaturehematopoieticcellsarealmostpresentintheblood.MarrowfindingsNormalbonemarrowAMLmarrowCytogeneticfindings診斷標準Diagnosis&ClassificationOthernewlydevelopedmethodsMorphology:thebonemarrowcellsareevaluatedaccordingtotheirsize,shape,andcontentofgranulesandthentheyareclassifiedwithrespectedtomaturity.Cytochemistrystaining:identificationofthechemicalcomponentsofcellsisconductedtodistinguishdifferenttypesofleukemia.Cytochemistryoftenusespecialcoloreddyes.AcuteleukemiaAMLALLM0:undifferentiatedAMLM1:Myeloblasticleukemia(withoutmaturation)M2:Myeloblasticleukemia(withmaturation)M3:promyelocyticleukemiaM4:MyelomonocyticleukemiaM5:MonocyticleukemiaM6:ErythroleukemiaM7:MegkaryoblasticleukemiaL1:MatureappearinglymphoblastsL2:ImmatureandvariouslyshapedlymphoblastsL3:Lymphoblastsarelargeanduniform.P142(CDtables)AlotofCDprovidescluesforthediagnosisFlowCytometryImmunohistochemistry
ImmnuophenotypingpanelusedinSt.JudeChildren’sresearchhospitalU.S.A.CD13CD33CD19CytoCD79aCD7CytoCD3AML----B-ALL----T-ALL----Byusingthismethodofanalysis,onecanmakeafirmdiagnosisin99%ofcases.免疫表型分型方案T細胞B細胞(4%)B細胞前體
CD7(敏感),cCD3(特異)CD19(敏感),cCD79a(特異)成熟T細胞(18%)前T細胞(6%)前B-細胞(9%)早期前-B細胞(52%)前-前-B細胞(11%)sIg,sIgInserttable90%ofthecaseswithleukemiahavenon-randomizedtranslocation.P118typesoftranslocationsCMLAML-M2AML-M3AML-M4AMLAML-M4E0Othernewdevelopedmethods鑒別診斷DifferentialDiagnosisPseudoleukemiaMyelodysplasticsyndromeNonleukemicpanc
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