急性淋巴细胞白血病2021.v4（英文）-NCCN肿瘤临床实践指南

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)AcuteLymphoblasticLeukemiarsionJanuaryNCCNGuidelinesforPatients®availableat:/patientsVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.esPanelDisclosuresPrintedbyMinTangon3/14/20227:25:27AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllesPanelDisclosuresphoblasticLeukemiadexrickABrownMDChaireSidneyKimmelComprehensiverCenteratJohnsHopkins*BijalShah,MD/Vice-Chair†MoffittCancerCenterAnjaliAdvani,MD†‡CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitutePatriciaAoun,MD,MPH≠CityofHopeNationalMedicalCenterMichaelW.Boyer,MD‡ξ€HuntsmanCancerInstituteattheUniversityofUtahPatrickW.Burke,MD†‡UniversityofMichiganRogelCancerCenterDanielJ.DeAngelo,MD,PhD†‡Dana-Farber/BrighamandWomen’senterShiraDinner,MD†‡RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityAmirT.Fathi,MD†‡ÞMassachusettsGeneralHospitalCancerCenterJordanGauthier,MD,MSc‡FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceNitinJain,MD†‡TheUniversityofTexasSuzanneKirby,MD‡DukeCancerInstituteMichaelaLiedtke,MD‡StanfordCancerInstituteMarkLitzow,MD‡MayoClinicCancerCenterAaronLogan,MD,PhD‡ξUCSFHelenDillerFamilyComprehensiveCancerCenterSelinaLuger,MD†AbramsonCancerCenterheUniversityofPennsylvaniaLoriJManess,MD‡Fred&PamelaBuffettCancerCenterStephanieMassaro,MD,MPH€‡YaleCancerCenter/SmilowCancerHospitalRyanJ.Mattison,MD†‡ÞUniversityofWisconsinCarboneCancerCenterWilliamMay,MD€UCLAJonssonComprehensiveCancerCenterOlalekanOluwole,MD‡Vanderbilt-IngramCancerCenterJaePark,MD†MemorialSloanKetteringCancerCenterAmandaPrzespolewski,DO‡RoswellParkComprehensiveCancerCenterSravantiRangaraju,MD†‡O'NealComprehensiveCancerCenteratUABJeffreyE.Rubnitz,MD,PhD€St.JudeChildren’sResearchHospital/TheUniversityofTennesseeHealthScienceCenterGeoffreyL.Uy,MD‡†ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineMadhuriVusirikala,MDξ‡UTSouthwesternSimmonsComprehensiveCancerCenterJamesK.Mangan,MD,PhD‡ξUCSanDiegoMooresCancerCenterBethLynn,RN,BSDeborahFreedman-Cass,PhDMalloryCampbell,PhDdiMScξBonemarrowtransplantation‡Hematology/HematologyoncologyÞInternalmedicine†Medicaloncology≠Pathology€Pediatriconcology§Radiotherapy/RadiationoncologyussionSectionngCommitteeVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:25:27AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.phoblasticLeukemiadexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.tNCCNutionsclickhereinicaltrialsmemberpxofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.oftheGuidelinesUpdatesDiagnosis(ALL-1)WorkupandRiskStratification(ALL-2)Ph+ALL(AYA/Adult)TreatmentInductionandConsolidationTherapy(ALL-3)Ph-ALL(AYA)TreatmentInductionandConsolidationTherapy(ALL-4)Ph-ALL(Adult)TreatmentInductionandConsolidationTherapy(ALL-5)Surveillance(ALL-6)upsforBALLALLAullaryInvolvementALLBtemicTherapyALLDeAssessmentALLFTheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.2022.Version4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:25:27AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.phoblasticLeukemiadexUpdatesinVersion4.2021oftheNCCNGuidelinesforAcuteLymphoblasticLeukemiafromVersion3.2021include:MS-1TheDiscussionsectionhasbeenupdatedtoreflectthechangesinthealgorithm.delinesforAcuteLymphoblasticLeukemiafromVersionincludeALL-7lapsedRefractoryDiseasepPh+B-ALL◊Thefollowingregimenhasbeenaddedasatreatmentoption:Brexucabtageneautoleucel(followingtherapythathasincludedTKIs)pPh-B-ALL◊Thefollowingregimenhasbeenaddedasatreatmentoption:Brexucabtageneautoleucel.•Footnotessadded:SeeNCCNGuidelinesforManagementofImmunotherapy-RelatedToxicities.ALL-D3of10•RegimensforRelapsedorRefractoryPh-PositiveB-ALLpOtherRecommendedRegimens:◊Thefollowingregimenhasbeenadded:Brexucabtageneautoleucel(followingtherapythathasincludedTKIs)◊Referenceadded:ShahBD,GhobadiA,OluwoleOO,etal.KTE-X19forrelapsed/refractoryadultB-cellacutelymphoblasticleukemia.Lancet2021;398:491-502.(AlsoonALL-D4of10)•Footnotepadded:SeeNCCNGuidelinesforManagementofImmunotherapy-RelatedToxicities.(AlsoonALL-D4of10)ALL-D4of10•RegimensforRelapsedorRefractoryPh-NegativeB-ALLpPreferredRegimens ◊Thefollowingregimenhasbeenadded:Brexucabtageneautoleucel(forB-ALL)UpdatesinVersion2.2021oftheNCCNGuidelinesforAcuteLymphoblasticLeukemiafromVersion1.2021include:ALL-C3of4•AsparaginaseToxicityManagementinpatientsyearsasparaginaseErwiniachrysanthemiErwiniaERWaand4)asparaginaseErwiniachrysanthemi(recombinant)-rywn(ERW-pSecondbulletrevised:TherearethreeinpatientsyearsasparaginaseErwiniachrysanthemiErwiniaERWaand4)asparaginaseErwiniachrysanthemi(recombinant)-rywn(ERW-•Hypersensitivity,Allergy,andAnaphylaxispSecondbulletrevised:ErwiniaERW,orERW-rywnmaybeiscommonlyusedasasecond-lineagentinpatientswhohavedevelopedasystemicallergicreactionoranaphylaxisduetoPEGhypersensitivity.•Footnoteaadded:ERWandERW-rywnareforpatientswhohadanallergicreactiontoE.coli-derivedasparaginase.ALL-D1of10•Footnotefadded:ForpatientswhodevelophypersensitivitytoE.coli-derivedasparaginase,ERWorERW-rywncanbesubstitutedasacomponentofthemulti-agentchemotherapeuticregimentocompletethefulltreatmentcourse.(AlsopagesALL-D2of10,andALL-D9of).•TheDiscussionsectionhasbeenupdatedtoreflectthechangesinthealgorithm.oupsforBALLALLAAlsopageALLAoteccConsiderdosemodificationsappropriateforpatientageandperformancestatusSeePrinciplesofSystemicTherapyoupsforBALLALLAAlsopageALLAoteccConsiderdosemodificationsappropriateforpatientageandperformancestatusSeePrinciplesofSystemicTherapyTreatmentofOlderAdultsyearsorAdultswithSubstantialComorbiditiesALL-D9of10).aneuploidyorfailedkaryotype.studiesinALLDatademonstratingtheeffectofWBCcountsonprognosisarelessfirmlyestablishedforadultsthanforthepediatricsupersededbyMRDquantificationaftertreatmentAlsopagesALLALLAALLAandALLFootnotejadded:ALLarisingfrompriorchemotherapyorunderlyinghematologicmalignancymaybeassociatedwithadverseoutcomes.ingandearlyevaluationandsearchforfamilyoranalternativedonorearlytransplantevaluationanddonorsearch.•RiskStratification,toppathway,added:andAdult.ALL-3rraycGHwithchromosomalmicroarrayCMAarraycGHincasesofSayginC,etal.BloodAdv2019;3:4228-4237.phoblasticLeukemiadexdelinesforAcuteLymphoblasticLeukemiafromVersionincludeALL-1•MolecularCharacterizationrecommendedencouragedforgenefusionsandpathogenicmutations,particularlyifknowntobeBCR-ABL1/Ph-negativeorPh-like.pThirdbulletrecommendedencouragedforgenefusionsandpathogenicmutations,particularlyifknowntobeBCR-ABL1/Ph-negativeorPh-like.ificationandclinicalriskgroups.ificationandclinicalriskgroups.ALL-1AFootnoteiaddedHighWBCcount(≥30x109/LforBlineageor≥100x109/LforTlineage)isFootnoteiaddedHighWBCcount(≥30x109/LforBlineageor≥100x109/LforTlineage)isconsideredahigh-riskfactorbasedonsomeALL-2•Ph+AYApathwaywascombinedwiththePh+Adultpathway.•RiskStratificationConsolidationTherapywasextensivelyrevised.Thefollowing:“Allogeneichematopoieticcelltransplantation(HCT),inappropriatecandidatesfollowedbycandidatesfollowedbytheoptiontoconsiderpost-HCTTKIorContinuemultiagentchemotherapy+TKIfollowedbytheoptionmaintenancetherapyTKIwasreplacedwith:omabTKIBALLorContinuemultiagentchemotherapycorticosteroidTKIorAllogeneicHCTinappropriatecandidatesttchemotherapycorticosteroidTKIorAllogenicHCTinappropriatecandidatesnotespAdded:TispreferredwhenpossibleSeeDiscussionAlsopagesALLAandALLBlinatumomabTKITKIintolerantrefractoryBALLorInotuzumabuctionpredictshighrelapseratesandshouldpromptevaluationforallogeneicHCTTherapyaimedateliminatingMRDpriortophoblasticLeukemiadexdelinesforAcuteLymphoblasticLeukemiafromVersionincludeandlevelspromptingallogeneicHCTshouldbeguidedbythespecifictreatmentprotocolbeingused.Ingeneral,MRDpositivityattheandlevelspromptingallogeneicHCTshouldbeguidedbythespecifictreatmentprotocolbeingused.Ingeneral,MRDpositivityatthederusinganderusinganalternativeandmorebroadlyactingTKISeePrinciplesofSystemicTherapyRegimensforPhPositiveoftionsincludeinalphabeticalorderbosutinibdasatinibimatinibnilotiniborponatinibDasatinibandimatinibarethepreferredTKIsforinductiontherapyponatinibisalsopreferredforthehyperCVADregimenNotallTKIshavebeendirectlystudiedwithinthecontextofeachspecificregimenandthepanelnotesthattherearelimiteddataforbosutinibinPh+ALL.UseofaspecificTKIshouldaccountforanticipatedpriorTKIintolerance,BCR-ABL1mutations,anddisease-relatedfeatures.Forcontraindicatedmutations,eeALLDofnagementALLCofAlsopageALLAemissionafterblinatumomabtreatmentispossibleallogeneicHCTshouldbeconsideredasageALLAnsnsincludeCNSprophylaxisSeeEvaluationandTreatmentofExtramedullaryInvolvementALLBOptimaltimingofHCTisnotclearForfitpatientsadditionaltherapyisrecommendedtoeliminateMRDpriortotransplantlogeneicHCTwithMRDisnotoptimalAlsopagesALLAandALLuggestthatforyoungerpatientsagedyparticularlyforthosewhoachieveMRDnegativityallogeneicHCTmaynotofferanadvantageoverchemotherapy+TKI...•Footnoteiiadded:ConsiderretestingforMRDatfirstavailableopportunity.(AlsopageALL-5)ALL-6•Surveillance,OtherGeneralMeasures,firstbulletrevised:Bonemarrowaspiratecanbeconsideredasclinicallyindicatedeveryatafrequencyofupto3–6monthsforatleast5years.ALL-7•Relapsed/RefractoryDiseasep"B"addedtoPh+ozogamicinbosutinibTKIozogamicinbosutinibTKIintolerantrefractoryB-ALL)...neticRiskGroupsforBALLALLALPDGFRAPDGFRBFGFRUPDATESVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ourEetalPhlikeacutelymphoblasticleukemiaahighrisksubtypeinadultsBloodprognosticprofileinpediatricB-cellprecursoracutelymphoblasticleukemia.ourEetalPhlikeacutelymphoblasticleukemiaahighrisksubtypeinadultsBloodprognosticprofileinpediatricB-cellprecursoracutelymphoblasticleukemia.JClinOncol2018;36:1240-1249.rationsdonotconferpoordiscontinueasparaginaseorholdasparaginaseuntil.0mg/dL,thenresumewithveryconsiderationfordosereductionandclosemonitoring.ContinuedHypodiploidALLisalsooftenassociatedwithTPlossoffunctionmutationsandLi-Fraumenisyndrome.ablekinaseactivationlesionsinPhlikeacutelymphoblasticleukemiaNEnglJMedprognosis.phoblasticLeukemiadexdelinesforAcuteLymphoblasticLeukemiafromVersionincludethresholdorotherclearevidenceofhypodiploidclone2014;371:1005-1015.009;360:470-480;StanullaM,DagdanE,ZaliovaM,etal.IKZF1plusdefinesanewminimalresidualdisease-dependentvery-poorpFootnotee:MullighanCG,SuX,ZhangJ,009;360:470-480;StanullaM,DagdanE,ZaliovaM,etal.IKZF1plusdefinesanewminimalresidualdisease-dependentvery-poorALL-BbeadministeredwithinitialLP•EvaluationandTreatmentofExtramedullaryInvolvement,thirdbullet,beadministeredwithinitialLPxicityManagementInotuzumabxicityManagementInotuzumabBlinatumomabandTisagenlecleucelertocilizumabforpatientswithrefractorysevereCRSALL-C(3of4)seToxicityManagementertocilizumabforpatientswithrefractorysevereCRSALL-C(3of4)seToxicityManagementthatthedoseofPEGorCalPEGshouldbecappedatvialIUulletrevisedForGradereactionsandGradereactionsrashflushingurticariaanddrugfeverCwithoutbronchospasmhypotensionedemaorneedforparenteralintervention,theasparaginasethatcausedthereactionmaybecontinuedwithconsiderationforantiallergypremedication(suchashydrocortisone,famotidineorranitidine,diphenhydramine,andacetaminophen).Measuresthatcanbeconsideredforpreventingorlimitingseverityofinfusionreactionsorhypersensitivityreactionsincludeslowingtheinfusiontohoursinfusingnormalsalineconcurrentlyanduseofpremedicationsprovidedabove.TDMforasparaginasetherapyusingtheserumasparaginaseactivity(SAA)isavailableasaCLIA-certifiedtestwithaturnaroundtimeaminimumtroughofIUmLHoweverdataindicatethatwhenSAAlevelsfallbelowIUmL,asparagineisnolongercompletelydepleted,andbeginstorebound,suggestinganoptimaldepleted,andbeginstorebound,suggestinganoptimaltroughof≥0.4IU/mL.Routinepremedicationhasgenerallybeenavoidedinthepastforfearofmasking”hypersensitivityreactions.However,giventhedifficultyindistinguishinghypersensitivityandnonallergicinfusionreactionsandtheavailabilityofTDM,universalpremedicationandTDMcanbeconsidered,whichcanreducetheincidenceandseverityofadverseeventsandtheneedforsubstitutionofpegaspargasewithErwinia.upportiveCareAsparaginaseToxicityManagementcontinuedHepatotoxicityfirstbulletrevisedFordirectbilirubineitherUPDATESVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.geALLDofnatumomabTKIgeALLDofnatumomabTKILLoradultpatientswithsubstantialcomorbiditiesseemabshouldbeconsideredinadditiontochemotherapyforCDpositiveeprimarilyusedininductiontherapyandadditionaltherapyisneededForpostinductioncomponentsseelistedreferencesAlsopageALLDAionsseeALLDofAlsopageALLDofientswhodevelopsevereSKCCALLregimenbasedonCCGregimendaunorubicinvincristineprednisoneandmethotrexatesagedyearsCCALLregimenbasedonCCGregimendaunorubicinvincristineprednisoneandmethotrexateerstartingMPTestingforbothTPMTandNUDTvariantstatusshouldbeconsideredespeciallyforpatientsofEast•Headingrevised:InductionRegimensforPh-PositiveB-ALL.ALLDof10.(AlsopageALL-D2of10)ntsespeciallyinpatientsyearsAlsopageALLDAevisedLinkerdrugregimendaunorubicinvincristinepegaspargaseandprednisonewithrituximabforCDpositivewithaugmentedpegaspargase(patientsaged<60years).phoblasticLeukemiadexdelinesforAcuteLymphoblasticLeukemiafromVersionincludeALL-D(1of10)ofSystemicTherapyALL-D(1of10)otnotesrevisedALLotnotesrevisedolTherAlsopageALLDAolTherAlsopageALLDAtnotesaddedtnotesaddedDAandALLDof•Footnoteremoved:Theseregimensareusedforinductiontherapyandadditionaltherapyisneeded.ALL-D(2of10)•AYAPatientspPreferredregimens,firstandlastoptions,removed:(ongoingstudyinpatientsaged<40years).pOtherRecommendedRegimensalternatingwithhigh-dosemethotrexateandcytarabine;withrituximabforCD20-positivedisease.◊Thirdoptionrevised:Hyperalternatingwithhigh-dosemethotrexateandcytarabine;withrituximabforCD20-positivedisease.AdultAdultPatients5yandwithoutsubstantialcomorbidities)alternatingwithhigh-dosemethotrexateandcytarabine;withrituximabforCD20-positivedisease.alternatingwithhigh-dosemethotrexateandcytarabine;withrituximabforCD20-positivedisease.UPDATESVersion4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.StatementaftertablerevisedFortreatmentofolderadultpatientsywithALLoradultpatientswithsubstantialcomorbiditiesseeALL9PrintedbyMinTangStatementaftertablerevisedFortreatmentofolderadultpatientsywithALLoradultpatientswithsubstantialcomorbiditiesseeALL9phoblasticLeukemiadexdelinesforAcuteLymphoblasticLeukemiafromVersionincludeCDpositivediseasepatientsaged<60years).FifthoptionrevisedLinkerdrugregimenrituximabdaunorubicinvincristineCDpositivediseasepatientsaged<60years).•Headingrevised:RegimensforRelapsed•Headingrevised:RegimensforRelapsedorRefractoryPh-PositiveB-ALL.–Blinatumomab±–Blinatumomab±TKI(forB-ALL)(TKIintolerant/refracory).–Inotuzumabozogamicin±bosutinib(forB-ALL)–Inotuzumabozogamicin±bosutinib(forB-ALL)(TKIintolerant/refractory).TheregimenslistedonALL-D4of10forPh-negativeB-ALLmaybeconsideredforPh-positiveB-ALLrefractorytoTKIs.edMOpADregimencategoryBmethotrexatevincristinepegaspargasedexamethasonewithrituximabforCDpositivediseaseandTKI.•Headingrevised:RegimensforRelapsedorRefractoryPh-NegativeB-ALL.elarabinealoneorelarabinealoneorincombinationegnelarabineetoposidecyclophosphamideforTALLrRRPhnegativeALLonlymethotrexatevincristinepegaspargasedexamethasonewithrituximabforCD20-positivedisease.Newsectionadded:PrinciplesofSystemicTherapy:RegimensforRelapsedorRefractoryPh-NegativeT-ALL.ALLDofandALLALLDofandALLD(7of10)andALL-D(8of10)•Referencesupdated.ALL-D(9of10)mentofOlderAdultsyearsorAdultswithALLSubstantialComorbiditiesAlsopageALLDofFootnotefrevised:TKIoptionsinclude(inalphabeticalorder):bosutinib,dasatinib,imatinib,nilotinib,orponatinib.DasatinibandimatinibarethepreferredTKIsforinductiontherapyponatinibisalsopreferredforthehyperCVADregimenNotallTKIshavebeendirectlystudiedwithinthecontextofeachspecificregimenandthepanelnotesthattherearelimiteddataforbosutinibinPh+ALL.UseofaspecificTKIshouldaccountforanticipatedpriorTKIintoleranceanddiseaserelatedfeatures.Forcontraindicatedmutations,seeALL-D3of10.•Minimal/MeasurableResidualDiseaseAssessmentpFirstbulletrevised:ThepreferredsampleforMRDassessmentisthefirstsmallvolume(ofupto3mL)pullofthebonemarrowaspirate,iffeasible.pThirdbullet,lastsentenceadded:IfvalidatedMRDassessmenttechnologywithappropriatesensitivity(atleast10-4)isnotavailablelocally,therearecommerciallyavailabletests.pSixthbullet,lastsentenceadded:Methodsnotachievingthesesensitivitylevelsarenotsuitable.BaselineflowcytometricandormolecularcharacterizationofleukemicclonetofacilitatesubsequentsurableresidualdiseaseMRDanalysisseeALLFKaryotypingofGbandedmetaphasechromosomesReversetranscriptaseBaselineflowcytometricandormolecularcharacterizationofleukemicclonetofacilitatesubsequentsurableresidualdiseaseMRDanalysisseeALLFKaryotypingofGbandedmetaphasechromosomesReversetranscriptasepolymerasechainreactionRTPCRtestingBCRABLinBALL(quantitativeorAdditionaloptionaltestsinclude:phoblasticLeukemiadexDIAGNOSIScutelymphoblasticsshouldundergoevaluationandtreatmentatspecializedcentersThediagnosisofALLgenerallyrequiresdemonstrationof≥20%bonemarrowlymphoblastsd,euponhematopathologyreviewofbonemarrowaspirateandbiopsymaterials,whichincludes:Comprehensiveflowcytometricimmunophenotypingf•MorphologicassessmentofWright-Giemsa–stainedbonemarrowaspiratesmears,andH&E–stainedComprehensiveflowcytometricimmunophenotypingfOptimalriskstratificationandtreatmentplanningrequiretestingmarroworperipheralbloodlymphoblastsforspecificrecurrentgeneticabnormalitiesusing:entgeneticabnormalitiesa•Interphasefluorescenceinsituhybridization(FISH)testing,includingprobesentgeneticabnormalitiesaqualitative)includingdeterminationoftranscriptsize(ie,p190vs.p210)isrecommendedparticularlyifknowntobeBCRABLPhnegativeorPhlikeisrecommendedparticularlyifknowntobeBCRABLPhnegativeorPhlikeg•Assessmentwithchromosomalmicroarray(CMA)/arraycGHincasesofaneuploidyorfailedkaryotype.ytogeneticandclinicalriskgroupshijinationoftheytogeneticandclinicalriskgroupshijcationonALLANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version4.2021,01/07/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ALL-1PrintedbyMinTangon3/14/20227:25:27AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.phoblasticLeukemiadexFOOTNOTESaSubtypes:B-celllymphoblasticleukemia/lymphomawithrecurrentgeneticabnormalitiesincludeshyperdiploidy,hypodiploidy,andcommonlyoccurringtranslocations:t(9;22)(q34.1;q11.2)[BCR-ABL1];t(v;11q23.3)[KMT2Arearranged];t(12;21)(p13.2;q22.1)[ETV6-RUNX1];t(1;19)(q23;p13.3)[TCF3-PBX1];t(5;14)(q31.1;q32.3)[IL3-IGH];Ph–like;B-lymphoblasticleukemia/lymphomawithiAMP21;earlyT-cellprecursorlymphoblasticleukemia.bCriteriaforclassificationofmixedphenotypeacuteleukemia(MPAL)shouldbebasedontheWHO2016criteria.Notethatin