兒童急性淋巴細(xì)胞白血病2022.v1-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)PediatricAcuteLymphoblasticLeukemiarsionOctoberVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:48:14AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexPatrickBrownMD/Chair€eSidneyKimmelComprehensiverCenteratJohnsHopkins*HirotoInaba,MD,PhD/Vice-Chair€St.JudeChildren'sResearchHospital/TheUniversityofTennesseeeCenterCancerResearchCenterianceJillBeck,MD€Fred&PamelaBuffettCancerCenterJongChungMD€prehensiveCancerCenterusanColaceMDMSCIeOhioStateUniversityComprehensivecerCenterJamesCancerHospitaldSoloveResearchInstituteinCurranMDxloanKetteringCancerCenterMariDallas,MD?€CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitutetiroDeOliveiraMDeCancerCenterRoswellParkComprehensiveCancerCenterCarrieKitko,MDx€Vanderbilt-IngramCancerCenterMDCancerCenterMDordCancerInstituteCathyLee-Miller,MD?€CarboneCancerCenteronsinigMDnshensiveCancerCenterrInstituteattheUniversityofUtahValentinaNardi,MD≠M(fèi)assachusettsGeneralHospitalCancerCenterJennaRossoff,MDx?RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityAnn&RobertH.LurieChildren'sHospitalofChicagoLauraSchuettpelz,MD,PhD€SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineBijalShah,MD€MoffittCancerCenterShilpaShahani,MD€CityofHopeNationalMedicalCenteranMDancerInstituteJessicaSun,MD?€DukeCancerInstituteDavidTeachey,MD€AbramsonCancerCenterattheUniversityofPennsylvania-ensHospitalofPhiladelphiaVictorWong,MD€UCSanDiegoMooresCancerCenter-RadyChildren'sHospitalofSanDiegoGregoryYanik,MD€UniversityofMichiganRogelCancerCenterdiMScFreedmanCassPhDesPanelDisclosuresxBonemarrowtransplantation?Hematology/Hematologyoncology≠Pathology€Pediatriconcology§Radiotherapy/Radiationoncology*DiscussionSectionWritingCommitteeVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:48:14AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexlievesthatthebestmanagementforlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.yoftheGuidelinesUpdatesDiagnosis(PEDALL-1)WorkupandRiskStratification(PEDALL-2)?B-ALLPh-negativeorPh-likeInductionandConsolidationTherapy(PEDALL-3)?B-ALLPh-positiveInductionandConsolidationTherapy(PEDALL-5)?T-ALLInductionandConsolidationTherapy(PEDALL-6)?InfantALLInductionandConsolidationTherapy(PEDALL-7)Surveillance(PEDALL-8)B-ALLFirstRelapseDisease(PEDALL-9)T-ALLFirstRelapseDisease(PEDALL-10)MultipleRelapseorRefractoryDisease(PEDALL-11)psforBALLPEDALLApportiveCarePEDALLBramedullaryInvolvementPEDALLCationsforVulnerablePopulationsPEDALLDionDefinitionsPEDALLEfSystemicTherapyPEDALLFEDALLGlDiseasePEDALLIllTransplantPEDALLJTheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2021.Version1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.cancerpredispositionsyndromesprinciplesofcancerriskaspossibleandwithinonehourofpresentationwithfever,andneutropenia,andorsepsis.forGeneticcancerpredispositionsyndromesprinciplesofcancerriskaspossibleandwithinonehourofpresentationwithfever,andneutropenia,andorsepsis.forGeneticFamilialHighRiskAssessmentBreastlfebrilefemalepatientsandinfantsorinanypatientwithassessmentandcounselingshouldbetakenintoconsideration(SeeanandPancreaticdexidelinesforPediatricAcuteLymphoblasticLeukemiafromVersionincludePEDALL-1Prophylaxisguidelines:clonetofacilitatesubsequentminimalresidualdiseaseMRD)analysis?Diagnosis,thirdbulletmodified:BaselinecharacterizationofleukemicclonetofacilitatesubsequentminimalresidualdiseaseMRD)analysisowcytometricandormolecularcharacterizationofleukemiconetofacilitatesubsequentminimalresidualdiseaseMRDanalysistropeniadurationofdaysowcytometricandormolecularcharacterizationofleukemiconetofacilitatesubsequentminimalresidualdiseaseMRDanalysistropeniadurationofdaysuntilcountrecoveryafterexpectedhematologicnadir(ANCexpectedhematologicnadir(ANC>200orAPC>500/mm3).rmicafunginorotherechinocandinantifungaldrugsduringinductionandpotentiallyduringotherhighintensityphases.ciatedechinocandinantifungaldrugsduringinductionandpotentiallyduringotherhighintensityphases.ciatedwithALLriskhavebeenreportedAcompletefamilyverandneutropeniaalthoughdenovomutationshavebeenreported.genitourinarysymptomsorwithaurinarycatheterinplacebefore?Footnotegenitourinarysymptomsorwithaurinarycatheterinplacebeforeempiricalantibioticsaredispensed.tisagenlecleucelisunclear.empiricalantibioticsaredispensed.ALLBofperipheralbloodandpersistentBALLBofFeverandneutropenia(continued),thirdbullet,secondsub-bulletwithdurableFeverandneutropenia(continued),thirdbullet,secondsub-bulletaddedInitiateormodifyantimicrobialtherapiesaccordinglyregistrationtrial,relapse-freeaddedInitiateormodifyantimicrobialtherapiesaccordinglypenetrateintotheCSFonly9%ofpatientsproceedingtoHCT(penetrateintotheCSFALLBof2018;378:439-448).SeeALLBof?Anthracycline-RelatedCardiotoxicity:Secondbullet,firstsub-(?Anthracycline-RelatedCardiotoxicity:Secondbullet,firstsub-ulletthirdsubulletthirdsubbulletmodifiedMitoxantroneMultiplytotaldosebyxmitoxantronehasbeenconsideredtobe4to5timesbyxmitoxantronehasbeenconsideredtobe4to5timesmorecardiotoxicmorecardiotoxicthandoxorubicin,butnewerdatasuggestitmightbeasmuchasbeasmuchas10timesmoretoxic).PEDALL-B6of9?HyperleukocytosispReferenceadded:LocatelliPEDALL-B6of9?HyperleukocytosispReferenceupdated:BrownPA,etal.JAMA2021;325:833-842.ahighWBCcountLmalepatients,thosewithaT-cellphenotypeinfantsandthosewithKMTAorBCRABLrearrangements.?InfectionControl:fornewlydiagnosedpatients,viralserologies(ie,HSVIgG,CMVIgGEBVpanelandquantitativeimmunoglobulinsieIgAIgM,IgG)shouldbeassessedmaybeconsidered.UPDATESVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:48:14AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexidelinesforPediatricAcuteLymphoblasticLeukemiafromVersioninclude?BehaviorandPsychosocialSupport:pSecondbulletadded:Neurocognitivemonitoringduringtherapyshouldbeconsideredforallpatients,givenestablishedriskforneurocognitivelateeffectsassociatedwithintrathecalchemotherapy.pThirdBulletadded:Neurocognitivemonitoringcouldoccuratcompletionoftreatmentand/oratschoolentryorre-entry.Baselineassessmentmaybeconsideredtoprovideacontextinwhichtoappreciatechange.pFourthbulletadded:Considerreferralforacomprehensiveneuropsychologicalassessmentifthereisevidenceofnewconcernsorchange.PEDALL-B8of9?CerebralThrombosis,Ischemia,orStroke:Firstbulletmodified:Discontinueasparaginase.Considerantithrombotictherapy.Ifsymptoms/signsfullyresolve,canresumeasparaginase.Considerantithromboticprophylaxiswhenresumingasparaginase.PEDALL-B9of9?Referenceshavebeenadded:pEganG,RobinsonPD,MartinezJPD,etal.Efficacyofantibioticprophylaxisinpatientswithcancerandhematopoieticstemcelltransplantationrecipients:Asystematicreviewofrandomizedtrials.CancerMed2019;8:4536-4546.pLehrnbecherT,FisherBT,PhillipsB,etal.Guidelineforantibacterialprophylaxisadministrationinpediatriccancerandhematopoieticstemcelltransplantation.ClinInfectDis2020;71:226-236.pFeijenEAM,LeisenringWM,StrattonKL,etal.Derivationofanthracyclineandanthraquinoneequivalenceratiostodoxorubicinforlate-onsetcardiotoxicity.JAMAOncol2019;5:864-871.PEDALL-C?EvaluationandTreatmentofExtramedullaryInvolvement:pSeventhbullet,sub-bulletremoved:IfTBIisdone,recommendeddosingis12–14Gyat1.5–2Gy/fraction.pSeventhbullet,sub-bulletadded:SeeConditioningRegimeninthePrinciplesofHematopoieticCellTransplant(PEDALL-J3of5)PEDALL-E2of3?RiskStratificationDefinitions:Tableheadingsmodified:LowFavorableRiskandStandardAverageRiskPEDALL-F5of12?RegimenComponentspPh-positiveALL:?Modified:StandardarmofCOGAALL1631(basedonCOGAALL1122/EsPhALLregimen):imatinibordasatinibc;combinedwithanHRbackboneoftheBerlin-Frankfurt-MünsterregimenpInduction:?Removed:Cyclophosphamide,mercaptopurine,cytarabine,methotrexate,imatinib/dasatinib?Added:EsPhALLbackbone(cyclophosphamide,mercaptopurine,cytarabine,methotrexate)+imatinib/dasatinibPEDALL-F6of12?Footnoteadded:ForpatientswithMRD≥5x10-4attheendofinductiontherapy,myeloidtypeconsolidationtherapy(eg,ADE/MAE)canbeconsidered.(StutterheimJ,etal.JClinOncol2021;39:652-662.)PEDALL-F7of12?Ph-negativeALLpOtherRecommendedRegimens:?Firstbulletmodified:UKALLR3backbonechemotherapyregimenPEDALL-F8of12?Ph-PositiveALLpOtherRecommendedRegimens:?Bulletremoved:Backbonechemotherapy+TKI,followedbyHCTafterCRachieved?Footnoteadded:HCTshouldbeconsideredafterCRachieved.PEDALL-F10of12?Footnoteumodified:TheCIBMTRtrackssafetyandefficacydatafollowingcommercialCART-celltherapy.Fordetailsandcellulartherapydatacollectionforms,see/DataManagement/DataCollectionForms/Pages/index.aspx.see/DataManagement/DataCollectionForms/Documents/4100/Rev5.0/4100R5.pdf.PEDALL-F11of12?Referenceshavebeenupdated.Version1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.dexidelinesforPediatricAcuteLymphoblasticLeukemiafromVersionincludePEDALLFofpSeventhbullet,firstsub-bullet,fourthPEDALLFof?Referenceshavebeenupdated.monitoringfrequencymaybe?Referenceshavebeenupdated.DALLGofrelapseorDALLGofDosingGuidelinesforThiopurinesBasedonTPMTPhenotypepSeventhbullet,firstsubDosingGuidelinesforThiopurinesBasedonTPMTPhenotypetechniques,abaselinesample(ie,priortocharacterizetheleukemiccloneModified:StartingdoseshouldbebasedontreatmentprotocolmayModified:Startingdoseshouldbebasedontreatmentprotocol(typically75mg/m2/day).PEDALL-I2(typically75mg/m2/day).?Modified:StartingdoseshouldbebasedontreatmentprotocolpBerryDA,ZhouS,HigleyModified:Startingdoseshouldbebasedontreatmentprotocol(typically60mg/m2/day).diseasewithclinicaloutcomeinpediatricand(typically60mg/m2/day).DALLGofleukemia.JAMADALLGofDosingGuidelinesforThiopurinesBasedonNUDT15PhenotypepCherianS,SomaLADosingGuidelinesforThiopurinesBasedonNUDT15PhenotypediseaseinBlymphoblasticleukemia/lymphomaAmJModified:StartingdoseshouldbebasedModified:Startingdoseshouldbebasedontreatmentprotocol(typically75mg/m2/day)(typically75mg/m2/day).pFirstbulletmodified:BothTBIandModified:StartingdoseshouldbebasedontreatmentprotocolhavebeenusedModified:Startingdoseshouldbebasedontreatmentprotocol(typically60mg/m2/day).RetrospectivestudiesRandomized(typically60mg/m2/day).ResponseCriteriaforBloodandBoneMarrow,thirdbullet,ResponseCriteriaforBloodandBoneMarrow,thirdbullet,firstsub-childrenwithALL.Non-TBI–containingregimensareundercurrentlletlletaddedNOTEMRDassessmentisnotincludedinmorphologicassessmentandshouldbeobtained(SeePEDALL-I)pThirdbulletadded:Forinfants:assessmentandshouldbeobtained(SeePEDALL-I)PEDALL-I1of2?MinimalResidualDisease:pSecondbulletmodified:MRDPEDALL-I1of2?MinimalResidualDisease:pSecondbulletmodified:MRDisanessentialcomponentofpatientevaluationoverthecourseofsequentialtherapy.IfavalidatedMRDassessmenttechnologywithappropriatesensitivity(atleast10-4)isnotavailablelocally,therearecommerciallyavailabletests.pFifthbulletmodified:ThemostfrequentlyemployedmethodsforMRDassessmentinclude6-colorflowcytometryassays...pSeventhbulletmodified:CurrentflowcytometryorPCRmethodscandetectleukemiccellsatasensitivitythresholdofatleast1x10-4(<0.01%)bonemarrowmononuclearcells(MNCs).PCR/NGSmethodscandetectleukemiccellsatasensitivitythresholdof<1x10-6(<0.0001%)boneMNCs.TheconcordanceratefordetectingMRDbetweenthesemethodsatthislevelofdetectionis>90%.isSeePEDALL-F,2of12.PEDALL-J5of5?Referencesadded:pPetersC,DalleJ-H,LocatelliF,etal.TotalbodyirradiationorchemotherapyconditioninginchildhoodALL:Amultinational,randomized,noninferiorityphaseIIIstudy.JClinOncol2021;39:295-307.pTomizawaD,MiyamuraT,ImamuraT,etal.Arisk-stratifiedtherapyforinfantswithacutelymphoblasticleukemia:areportfromtheJPLSGMLL-10trial.Blood2020;136:1813-1823.generallyhighgenerallyhighMethodsnotachievingthesesensitivitylevelsarenotrecommended.Baselineflowcytometricandormolecularcharacterizationofleukemicclonetofacilitatesubsequentminimalresidualdisease(MRD)analysisi(seePEDALL-I)ReversetranscriptasepolymerasechainreactionRTPCRtestingBCRABLinBaselineflowcytometricandormolecularcharacterizationofleukemicclonetofacilitatesubsequentminimalresidualdisease(MRD)analysisi(seePEDALL-I)ReversetranscriptasepolymerasechainreactionRTPCRtestingBCRABLinBALL(quantitativeorAdditionaloptionaltestsinclude:dexDIAGNOSISacutelymphoblasticThediagnosisofALLgenerallyrequiresdemonstrationof≥20%bonemarrowlymphoblastse,f,guponhematopathologyreviewofbonemarrowaspirateandbiopsymaterials,whichincludes:mprehensiveflowcytometricimmunophenotypingh?MorphologicassessmentofWright-Giemsa–stainedbonemarrowaspiratesmears,andhematoxylinandeosin(H&E)–stainedmprehensiveflowcytometricimmunophenotypinghONOptimalriskstratificationandtreatmentplanningrequiretestingmarroworperipheralbloodlymphoblastsforspecificrecurrentgeneticabnormalitiesusing:?KaryotypingofG-bandedmetaphasechromosomesmajorrecurrentgeneticabnormalitiesb?Interphasefluorescenceinsituhybridization(FISH)testing,includingprobesmajorrecurrentgeneticabnormalitiesbqualitative)includingdeterminationoftranscriptsize(ie,p190vs.p210)pIfBCR-ABL1negative:encouragetestingforgenefusionsandmutations?Additionalassessment(eg,microarraycGH)incasesofaneuploidyorfailedkaryotype?Assessmentofvariouspotentiallyactionableorprognosticmutations(seeGeneticRiskGroups[PEDALL-A])CLASSIFICATION?Together,thesestudiesallowdeterminationoftheWorldHealthOrganization(WHO)ALLsubtypesandgeneticriskgroups(seeGeneticRiskGroupsforB-ALL[PEDALL-A])?PatientsshouldundergoevaluationandtreatmentatspecializedcentersFootnotesonPEDALLANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PEDALL-1PrintedbyMinTangon7/14/20229:48:14AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexFOOTNOTESaThepediatricALLpanelconsiders“pediatric”toincludeanypatientaged18yearsandyounger,andcertainadolescentandyoungadult(AYA)patientsolderthan18yearsofage.PracticepatternsvarywithregardtoAYApatientsfromcentertocenterintermsofwhetherALLpatientsaretreatedprimarilybypediatricoradultoncologists.ThisguidelineisintendedtoapplytoAYApatientstreatedinapediatriconcologysetting,andthismayincludepatientsuptoage30years.TheNCCNGuidelinesforAcuteLymphoblasticLeukemiaareintendedtoapplytoAYApatientstreatedinanadultoncologysetting.bSubtypes:B-celllymphoblasticleukemia/lymphomawithrecurrentgeneticabnormalitiesincludeshypodiploidy,hyperdiploidy,andcommonlyoccurringtranslocations:t(9;22)(q34.1;q11.2)[BCR-ABL1];t(v;11q23.3)[KMT2Arearranged];t(12;21)(p13.2;q22.1)[ETV6-RUNX1]dual-colorprobesettodetectcryptict(12;21),whichwillalsoallowdetectionofiAMP21(when≥5copiesoftheRUNX1genearedetected);t(1;19)(q23;p13.3)[TCF3-PBX1];t(5;14)(q31.1;q32.3)[IL3-IGH];B-celllymphoblasticleukemia/lymphoma,nototherwisespecified;B-lymphoblasticleukemia/lymphoma,BCR-ABL1–like;B-lymphoblasticleukemia/lymphomawithiAMP21;andearlyT-cellprecursor(ETP)lymphoblasticleukemia.AdditionalFISHprobesthatmaybeusefulinclude:centromericprobesforchromosomes4,10,and17todetecthyperdiploidy;CDKN2Aat9p21.3todetectdeletions;probestodetectcryptict(X;14)(p22;q32)/t(Y;14)(p11;q32)IGH-CRLF2rearrangements;andprobestodetectcrypticJAK2andFGFR1rearrangements.cCriteriaforclassificationofmixedphenotypeacuteleukemia(MPAL)shouldbebasedontheWHO2016criteria.NotethatinALL,myeloid-associatedantigenssuchasCD13andCD33maybeexpressed,andthepresenceofthesemyeloidmarkersdoesnotexcludethediagnosisofALL,norisitassociatedwithadverseprognosis.dBurkittleukemia/lymphoma;seetheNCCNGuidelinesforB-CellLymphomas.eWhiletheseguidelinespertainprimarilytopatientswithleukemia,patientswithlymphoblasticlymphoma(LL)(B-orT-cell)wouldlikelyalsobenefitfromALL-likeregimens.SuchpatientsshouldbetreatedinacenterthathasexperiencewithLL.fIftherearesufficientnumbersofcirculatinglymphoblasts(atleast1,000permicroliterasageneralguideline)andclinicalsituationprecludesbonemarrowaspirateandbiopsy,thenperipheralbloodcanbesubstitutedforbonemarrow.gInmanytreatmentprotocols,avalueof>25%marrowblastsisusedtodefineleukemia.Unlikewithmyeloidleukemias,thereisnoagreed-uponlowerlimitfortheproportionofblastsrequiredtoestablishadiagnosisofALL.Ingeneral,thediagnosisshouldbeavoidedwhenthereare<20%blasts.PresentationsofALLwithlowblastcountsareuncommon;thereisnocompellingevidencethatfailuretotreatapatientwhenthereare<20%marrowlymphoblastshasanadverseeffectonoutcome.SwerdlowSH,CampoE,HarrisNL,etal.WHOClassificationofTumoursofHaematopoieticandLymphoidTissues.Revised4thed.IARCPress:Lyon2017.hThefollowingimmunophenotypicfindingsareparticularlynotable:CD10negativitycorrelateswithKMT2Arearrangement(KMT2Ar);ETPT-ALL(typicallylackingexpressionofCD5,CD8,andCD1aandexpressionofoneormoremyeloid/stemcellmarkers);CD20positivity:definitionnotclear,moststudieshaveused>20%ofblastsexpressingCD20;andCRLF2overexpressionasasurrogateforgenomicalterationsoftheCRLF2gene(HarveyRC,WoodBL,ChemIM,etal.IdentificationofCRLF2genomiclesionsinpatientswithpediatricB-precursoracutelymphoblasticleukemia[BCPALL]byflowcytometryorquantitativeRT-PCR:AChildren'sOncologyGroup[COG]Study.Blood2012;120:2529).FlowcytometricDNAploidyanalysiscouldbeconsideredforrapididentificationofhyperdiploidandhypodiploidB-ALL.iByeitherflowcytometricanalysisorbyidentificationofclonalimmunoglobulinorT-cellreceptorgenerearrangements.jTheBCR-ABL1–like(Ph-like)phenotypeisassociatedwithrecurrentgenefusionsandmutationsthatactivatetyrosinekinasepathwaysandincludesgenefusionsinvolvingABL1,ABL2,CRLF2,CSF1R,EPOR,JAK2,orPDGFRBandmutationsinvolvingCRLF2,FLT3,IL7R,SH2B3,JAK1,JAK3,andJAK2(incombinationwithCRLF2genefusions).Testingfortheseabnormalitiesatdiagnosismayaidinriskstratification.Low-densityarray(LDA)(HarveyRC,etal.Blood2013;122:21),next-generationsequencing(NGS)-basedassays,andmultiplexRT-PCRareusedtodetectasignatureorcrypticrearrangementsandmutationscharacteristicofBCR-ABL1–likeALL.Thesafetyandefficacyoftargetedagentsinthispopulationisanareaofactiveresearch.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PEDALL-1AVersion1.2022,10/01/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ncerriskassessmentandcounselingshouldbetakenintoconsideration(SeeNCCNGuidelinesformutationshavebeenreported.PrintedbyMinTangon7/14/20229:48:14AM.ncerriskassessmentandcounselingshouldbetakenintoconsideration(SeeHYPERLINK"/professionals/physician_gls/pdf/genet