内科学第六篇 第九章 白血病.ppt

第六篇血液系统疾病 第九章 白血病 Leukemia 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 Erythrocytes transportoxygen NeutrophilBasophilEosinophilMonocytes Macrophage Defenseagainstinfection Platelets Mediatebloodclotting T lymphocytes antigenpresenting B lymphocytesPlasmacell Sourceofantibodies Pluripotentialstemcells Myeloidstemcells Lymphoidstemcells Unipotentialprogenitorcells Immaturehematopoieticcells maturehematopoieticcells Hematopoiesiscomposesoftheoptionsofcommitmenttodifferentlineagesandtheprogressivestagesofmaturationatwhichpartialorcompletearrestcanoccur resultsinthewidearrayofmalignantdisease Leukemia Stemcell Progenitorcell Immaturecell Maturecell AccumulationofmutationsofDNAwithinapluripotentialstemcellorveryearlyprogenitorcellgivesrisetoleukemicstemcells Normalstemcell Leukemicstemcell Etiology Pathogenesis EnvironmentalfactorsAcquireddiseases LesionstotheDNA Clonalexpansion Alotofenvironmentalfactorshasbeenreportedtocauseleukemia However onlyfourofthemarefirmlyestablishedcausalagents Theyare IrradiationexposureChronicbenzeneexposureChemotherapeuticagentsLeukemiavirusinfection Environmentalfactorscauseleukemia Inheritedsyndromessuchasataxia telangiectasia downsyndromepredisposetosubsequentdevelopmentofleukemia Usually thesekindsofsyndromessharethecommonfeaturesthattheyallhavehereticdefectsintheirgenomegavebytheirparents Inheritedsyndromespredisposetoleukemia Acquireddiseasepredisposetoleukemia Leukemiamayalsodevelopfromtheprogressionofotherclonaldisordersofhematopoieticstemcells Ploycythemiavera idiopathicmyelofibrosis etc LeukemiaClassification Thereareatleastdozensofvarietiesofleukemia Theyareclassifiedbyhowquicklyitprogresses Acuteleukemiaisfast growingandcanoverrunthebodywithinafewweeksormonths ByContrast chronicleukemiaisslow growingandprogressivelyworsenoveryears Acuteversuschronicleukemia Acute thebloodcellsofacuteleukemiaremaininanimmaturestate sotheyreproduceandaccumulateveryrapidly Therefore theyneedtreatmentimmediately otherwisethediseasemaybefatalwithinfewmonthsChronic inChronicleukemia thebloodcellseventuallymature orpartiallymature Buttheyarenot normal Theyremaininthebloodmuchlongerthannormalbloodcellsandtheycannotactfunctionalcellswell Myelogenousversuslymphocyticleukemia Iftheleukemiccellsarisefrommyeloidpluripotentialstemcells myeloidleukemia Iftheleukemiccellsarisefromlymphocyticpluripotentialstemcells lymphocyticleukemia Clinicalmanifestations Leukemichematopoiesis Normalhematopoiesis marrowfailure Infiltration Marrowfailure Anemia lossoferythocytes fatigues pallorweakness reducedexercisetoleranceFeverandinfection Poorinfectionfighters Abnormalbleeding lossofplatelets Infiltrations Oraltissue swollenpainful andbleedinggumsSplenomegalyandhepatomegalyLymphnodeenlargementBoneorjointpainCNS headaches seizures weakness blurredvisionandvomiting BloodtestfindingsAnemiaisaconstantfeature Nucleatedredcellsorimmatureredbloodcellmaybepresent Thrombocytopeniaisnearlyalwayspresentatthetimeofdiagnosis Thetotalleukocytecountscanbehigh normalorlow Immaturehematopoieticcellsarealmostpresentintheblood Marrowfindings Normalbonemarrow AMLmarrow Cytogeneticfindings Diagnosis Classification Othernewlydevelopedmethods Morphology thebonemarrowcellsareevaluatedaccordingtotheirsize shape andcontentofgranulesandthentheyareclassifiedwithrespectedtomaturityCytochemistrystaining identificationofthechemicalcomponentsofcellsisconductedtodistinguishdifferenttypesofleukemia Cytochemistryoftenusespecialcoloreddyes Acuteleukemia AML ALL M0 undifferentiatedAMLM1 Myeloblasticleukemia withoutmaturation M2 Myeloblasticleukemia withmaturation M3 promyelocyticleukemiaM4 MyelomonocyticleukemiaM5 MonocyticleukemiaM6 ErythroleukemiaM7 MegkaryoblasticleukemiaL1 MatureappearinglymphoblastsL2 ImmatureandvariouslyshapedlymphoblastsL3 Lymphoblastsarelargeanduniform P142 CDtables AlotofCDprovidescluesforthediagnosis FlowCytometry Immunohistochemistry 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 sIg Inserttable 90 ofthecaseswithleukemiahavenon randomizedtranslocation P118typesoftranslocations CML AML M2 AML M3 AML M4 AML AML M4E0 Othernewdevelopedmethods DifferentialDiagnosis Pseudoleukemia Myelodysplasticsyndrome Nonleukemicpancytopenia Treatment SupportivecaresandpreparationofthepatientsAntileukemictherapyTherapyofthecentralnervoussystemStemcelltransplantation AnemiaHemorrhageInfection HematologicalsupportTransfusionofPlateletsTransfusionofpackedredcellsTransfusionsofgranulocytesTransfusionsofIgG InfectioncontrolSpecialprecautions protectiveisolation Eliminationofcontaminatedfoods Oralanddigestivesystemcare Broadspectrumantibiotics GM CSFadministration Antileukemictherapy Chemotherapytokillleukemiacellsusingstronganti cancerdrugs Treatmentphases Inductiontherapy theaimistobringaboutremission thatisleukemiccellsarenolongerfoundinthebonemarrowandtherecoveryofnormalhematopoiesisPost remissiontherapy toeliminateanyleukemiacellspotentialhidinginthebody Specialsubtypes AcutepromyelocyticLeukemia APL becauseofthesmallparticles procoagulants insidetheAPLcell DICarecommonlyseeninthistypeofAML Normal APL GenesessentialfordifferentiationareshutdownbythefusionproteinsPML RARalpha Differentiationagents all transretinoicacid arsenictrioxide Hyperleukecytosis causeabatchofcomplicationsandshouldbetreatedusingleukapheresis exchangingtransfusion orpreinductiontreatmentpriortointensivechemotherapy Acuteleukemiaover60yearsofageislessresponsivetochemotherapyStandardtwo drugstherapycanbeused CR30 Intoleranttostandardtherapy Low doseofAra Ccanbeusedfor14 28days TherapyoftheCNSleukemia TheCNSisafrequentsanctuarysiteforleukemiccellsbecausemostofthechemotherapydrugsarenotabletoreachtheCNS SometypesofacuteleukemiahavetendencytobewithCNSleukemiasuchasAML M4 M5 ALL Intrathecalchemotherapy Cranialirradiation Stemcelltransplantations ThemainpurposeofBMTandPBSCTincancertreatmentistomakeitpossibleforpat