第六篇 第九章 白血病

第六篇血液系统疾病

第九章白血病(Leukemia)周剑峰学时数：3学时讲授目的和要求1.掌握急、慢性白血病的临床表现，实验室检查及诊断标准，治疗原则。2.熟悉急性白血病FAB分型，联合化疗的原则，完全缓解的概念。讲授主要内容概述病因和发病机制临床表现实验室检查诊断标准鉴别诊断治疗概述Erythrocytes:transportoxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefenseagainstinfectionPlatelets:MediatebloodclottingT-lymphocytes:antigenpresentingB-lymphocytesPlasmacell:SourceofantibodiesPluripotentialstemcellsMyeloidstemcellsLymphoidstemcellsUnipotentialprogenitorcellsImmaturehematopoieticcellsmaturehematopoieticcellsHematopoiesiscomposesoftheoptionsofcommitmenttodifferentlineagesandtheprogressivestagesofmaturationatwhichpartialorcompletearrestcanoccur,resultsinthewidearrayofmalignantdisease-Leukemia.StemcellProgenitorcellImmaturecellMaturecellAccumulationofmutationsofDNAwithinapluripotentialstemcellorveryearlyprogenitorcellgivesrisetoleukemicstemcells.NormalstemcellLeukemicstemcell病因和发病机制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临床表现ClinicalmanifestationsLeukemichematopoiesisNormalhematopoiesismarrowfailureInfiltrationMarrowfailureAnemia(lossoferythocytes):fatigues,pallorweakness,reducedexercisetolerance.Feverandinfection(Poorinfectionfighters).Abnormalbleeding(lossofplatelets).InfiltrationsOraltissue:swollenpainful,andbleedinggums.Splenomegalyandhepatomegaly.Lymphnodeenlargement.Boneorjointpain.CNS-headaches,seizures,weakness,blurredvisionandvomiting.实验室检查

BloodtestfindingsAnemiaisaconstantfeature.Nucleatedredcellsorimmatureredbloodcellmaybepresent.Thrombocytopeniaisnearlyalwayspresentatthetimeofdiagnosis.Thetotalleukocytecountscanbehigh,normalorlow.

Immaturehematopoieticcellsarealmostpresentintheblood.MarrowfindingsNormalbonemarrowAMLmarrowCytogeneticfindings诊断标准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细胞B细胞（4%）B细胞前体

CD7（敏感），cCD3（特异）CD19(敏感),cCD79a(特异)成熟T细胞（18%）前T细胞（6%）前B-细胞（9%）早期前-B细胞（52%）前-前-B细胞（11%）sIg,sIgInserttable90%ofthecaseswithleukemiahavenon-randomizedtranslocation.P118typesoftranslocationsCMLAML-M2AML-M3AML-M4AMLAML-M4E0Othernewdevelopedmethods鉴别诊断DifferentialDiagnosisPseudoleukemiaMyelodysplasticsyndromeNonleukemicpanc