血液系统疾病-白血病

第六篇血液系统疾病第九章白血病(Leukemia)学时数：2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:transportoxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefenseagainstinfectionPlatelets:MediatebloodclottingT-lymphocytes:antigenpresentingB-lymphocytesPlasmacell:SourceofantibodiesLeukemiaClassificationThereareatleastdozensofvarietiesofleukemia.Theyareclassifiedbyhowquicklyitprogresses.Acuteleukemiaisfast-growingandcanoverrunthebodywithinafewweeksormonths.ByContrast,chronicleukemiaisslow-growingandprogressivelyworsenoveryearsAcuteversuschronicleukemiaAcute:thebloodcellsofacuteleukemiaremaininanimmaturestate,sotheyreproduceandaccumulateveryrapidly.Therefore,theyneedtreatmentimmediately,otherwisethediseasemaybefatalwithinfewmonthsChronic:inChronicleukemia,thebloodcellseventuallymature,orpartiallymature.Buttheyarenot“normal”.TheyremaininthebloodmuchlongerthannormalbloodcellsandtheycannotactfunctionalcellswellMyelogenousversuslymphocyticleukemiaIftheleukemiccellsarisefrommyeloidpluripotentialstemcells:myeloidleukemiaIftheleukemiccellsarisefromlymphocyticpluripotentialstemcells:lymphocyticleukemiaClinicalmanifestationsLeukemichematopoiesisNormalhematopoiesismarrowfailureInfiltrationMarrowfailureAnemia(lossoferythocytes):fatigues,pallorweakness,reducedexercisetoleranceFeverandinfection(Poorinfectionfighters)Abnormalbleeding(lossofplatelets)InfiltrationsOraltissue:swollenpainful,andbleedinggumsSplenomegalyandhepatomegalyLymphnodeenlargementBoneorjointpainCNS-headaches,seizures,weakness,blurredvisionandvomitingBloodtestfindingsAnemiaisaconstantfeature.Nucleatedredcellsorimmatureredbloodcellmaybepresent.Thrombocytopeniaisnearlyalwayspresentatthetimeofdiagnosis.Thetotalleukocytecountscanbehigh,normalorlow.ImmaturehematopoieticcellsarealmostpresentinthebloodMorphology:thebonemarrowcellsareevaluatedaccordingtotheirsize,shape,andcontentofgranulesandthentheyareclassifiedwithrespectedtomaturityCytochemistrystaining:identificationofthechemicalcomponentsofcellsisconductedtodistinguishdifferenttypesofleukemia.CytochemistryoftenusespecialcoloreddyesAcuteleukemiaAMLALLM0:undifferentiatedAMLM1:Myeloblasticleukemia(withoutmaturation)M2:Myeloblasticleukemia(withmaturation)M3:promyelocyticleukemiaM4:MyelomonocyticleukemiaM5:MonocyticleukemiaM6:ErythroleukemiaM7:MegkaryoblasticleukemiaL1:MatureappearinglymphoblastsL2:ImmatureandvariouslyshapedlymphoblastsL3:LymphoblastsarelargeanduniformImmnuophenotypingpanelusedinSt.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DifferentialDiagnosisPseudoleukemiaMyelodysplasticsyndromeNonleukemicpancytopeniaTreatment1.Supportivecaresandpreparationofthepatients2.Antileukemictherapy3.Therapyofthecentralnervoussystem4.StemcelltransplantationInfectioncontrolSpecialprecautions:protectiveisolationEliminationofcontaminatedfoodsOralanddigestivesystemcareBroadspectrumantibioticsGM-CSFadministrationTreatmentphasesInductiontherapy:theaimistobringaboutremission,thatisleukemiccellsarenolongerfoundinthebonemarrowandtherecoveryofnormalhematopoiesisPost-remissiontherapy:toeliminateanyleukemiacellspotentialhidinginthebodyNormalAPLGenesessentialfordifferentiationareshutdownbythefusionproteinsPML-RARalphaTherapyoftheCNSleukemiaTheCNSisafrequentsanctuarysiteforleukemiccellsbecausemostofthechemotherapydrugsarenotabletoreachtheCNS.SometypesofacuteleukemiahavetendencytobewithCNSleukemiasuchasAML(M4,M5),ALLStemcelltransplantationsThemainpurposeofBMTandPBSCTincancertreatmentistomakeitpossibleforpatientstoreceiveveryhighdosesofchemotherapyand/orradiationtherapy.Inaddition,re-establishednormalhematopoiesisandimmunesystembythehealthystemcellsfightagainstleukemiaeffectively.SoitchangethevisioninthemedicalhistorythatleukemiaisincurablemalignanciesThreetypesoftransplantationperformedAllogeneictransplantation(HLA-matchedindividualdonors)Syngeneictransplantation:identicaltwinsAutologoustransplantation:patientsreceivetheirownstemcellsClinicalresultsofstemcelltransplantation0%10%20%30%40%50%60%70%80%90%123AMLALLCMLFive-yearsdiseasefreesurvivalrateTransplantationChemotherapyChronicmyelogenousleukemia(CML)复习思考题1.慢性粒细胞白血病与类白血病反应的鉴别要点？2.白血病完全缓解的标准？为何要进行巩固、强化化疗？3.骨髓增生异常综合征的分型、临床表现、与急性白血病的关系？