慢性粒細胞白血病英文

CHRONICMYELOIDLEUKAEMIADrRoslineHassanDepartmentofHaematologySchoolofMedicalSciencesUniversitiSainsMalaysiaLeukaemiasWhatareLeukemiasNeoplasmofwhitebloodcellanditsprecursorClonalproliferationsandaccumulationofcellsinmarrowClassifyasAcuteleukaemiasChronicleukaemiasTypesofLeukaemiaAcute:NomaturationbeyondblastChronic:MaturationbeyondblastLymphocytic(BorTlineage)ALLCLLMyeloid–granulocytesErythroidsMonocytesPlateletsAMLCMLIntroduction-CMLClonalmalignantmyeloproliferativedisordercharacterizedbyincreasedproliferationofthegranulocyticcelllinewithoutthelossoftheircapacitytodifferentiateResultsinincreasesinmyeloidcells,erythroidcellsandplateletsinperipheralbloodandmarkedmyeloidhyperplasiainthebonemarrowOriginateinasingleabnormalhaemopoieticstemcellIntroduction-CMLIncidence:1per100,000(UK)Accountsfor7-15%ofallleukaemiainadultsMedianage:53yearsAllagegroups,includingchildren,canbeaffectedIntroduction-CMLEtiologyNotclearLittleevidenceofgeneticfactorslinkedtothediseaseIncreasedincidenceSurvivorsoftheatomicdisastersatNagasaki&HiroshimaPostradiationtherapyLeukaemogenesisLeukaemogenesisPhiladelphiachromosomeisanacquiredcytogeneticanomalythatischaracterizesinallleukaemiccellsinCML90-95%ofCMLptshavePhchromosomeReciprocaltranslocationofchromosome22andchromosome9LeukaemogenesisBCR(breakpointclusterregion)geneonchromosome22fusedtotheABL(Ablesonleukemiavirus)geneonchromosome9Phchromosomeisfoundonmyeloid,monocytic,erythroid,megakaryocytic,B-cellsandsometimesT-cellproofthatCMLderivedfrompluripotentstemcellLeukaemogenesisMolecularconsequenceofthet(9;22)isthefusionproteinBCR–ABL,whichhasincreasedintyrosinekinaseactivityBCR-ABLproteintransformhematopoieticcellssothattheirgrowthandsurvivalbecomeindependentofcytokinesItprotectshematopoieticcellsfromprogrammedcelldeath(apoptosis)ClinicalFeaturesDiseaseisbiphasic,sometimestriphasic40%asymptomaticChronicphaseSplenomegalyoftenmassiveSymptomsrelatedtohypermetabolismWeightlossAnorexiaLassitudeNightsweatsClinicalFeaturesClinicalfeaturescont…FeaturesofanaemiaPallor,dyspnoea,tachycardiaAbnormalplateletfunctionBruising,epistaxis,menorrhagiaHyperleukocytosisthrombosisIncreasedpurinebreakdown:goutVisualdisturbancesPriapismLabfeaturesPeripheralbloodfilmAnaemiaLeukocytosis(usu>25x109/L,freq>100x109/LWBCdifferentialshowsgranulocytesinallstagesofmaturationBasophiliathrombocytosisLabfeaturesBonemarrowHypercellular(reducedfatspaces)Myeloid:erythroidratio–10:1to30:1(N:2:1)Myelocytepredominantcell,blastsless10%Megakaryocytesincreased&dysplasticIncreasereticulinfibrosisin30-40%LabfeaturesOtherlabfeatures:NAPreducedSerumB12andtranscobalaminincreasedSerumuricacidincreasedLactatedehydrogenaseincreasedCytogenetic:PhiladelphiachromosomeLaboratory-summaryLabinvestigationtoconfirmdiagnosisFullbloodpictureNeutrophilalkalinephosphataseBonemarrowcytogeneticPhasesAcceleratedphaseMediandurationis3.5–5yrsbeforeevolvingtomoreaggressivephasesClinicalfeaturesIncreasingsplenomegalyrefractorytochemoIncreasingchemotherapyrequirementLabfeaturesBlasts>15%inbloodBlast&promyelocyte>30%inbloodBasophil20%inbloodThrombocytopeniaCytogenetic:clonalevolutionPhasesBlasticphaseResemblesacuteleukaemiaDiagnosisrequires>30%blastinmarrow2/3transformtomyeloidblasticphaseand1/3tolymphoidblasticphaseSurvival:9mosvs3mos(lymvsmyeloid)GeneralManagementDiscussionwithfamilyThedisease&diagnosisPrognosisChoicesoftreatmentCytotoxicdrugvsbonemarrowtransplantSideeffectCML-principlesoftreatmentRelievesymptomsofhyperleukocytosis,splenomegalyandthrombocytosisHydrationChemotherapy(bulsuphan,Hydoxyurea)Controlandprolongchronicphase(non-curative)alphainterferon+chemotherapyimatinibmesylatechemotherapy(hydroxyurea)CML-principlesoftreatmentTreatmentcont…Eradicatemalignantclone(curative)allogeneictransplantationalphainterferon?imatinibmesylate/STI571?(Thyrosinekinaseinhibitor)ChemotherapyBusulphanAlkylatingagentPreferredinolderpts(notcandidatefortransplant)Sideeffect:prolongedmyelosuppressionPulmonaryfibrosisSkinpigmentationinfertilityChemotherapyHydoxyuresFewersideeffectActsbyinhibitingtheenzymeribonucleotidereductaseHaematologicalremissionsobtainin80%forbothdrugsHoweverdiseaseprogressionnotalteredandpersistenceofPhchromosomecontainingcloneChemotherapyRecombinanthumanα-InterferonProlongchronicphaseandincreases