儿童侵袭性成熟B细胞淋巴瘤2022.v2-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)PediatricAggressiveMatureB-CellLymphomasersionSeptemberVersion2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexMatthewBarthMD/Chair€ComprehensiveCancerCenter*AnaC.Xavier,MD/Vice-Chair€Children'sofAlabama/O'NealComprehensiveCancerCenteratUABSaroArmenian,DO,MPH€‡CityofHopeNationalMedicalCenternthonyNAudinoMDeOhioStateUniversityComprehensivecerCenterJamesCancerHospitaldSoloveResearchInstituteDavidBloom,MDфUniversityofMichiganRogelCancerCenterJongChungMD€prehensiveCancerCenteresMDrBostonChildrensCancerdBloodDisordersCenterdrensHospitaloMooresCancerCenterJamesB.Ford,DO€Fred&PamelaBuffettCancerCenterCancerCenteresPanelDisclosuresRabiHanna,MD€ξCaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussignstituteRobertHayashi,MD€ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineCathyLee-Miller,MD€UniversityofWisconsinCarboneCancerCenterAndreaJuditMachnitz,MD€фTheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsnsHospitalColoradoofColoradoCancerCenterDordCancerInstitutePaulL.Martin,MD,PhD€ξDukeCancerCenterDavidMcCall,MD€TheUniversityofTexascoMDnshensiveCancerCenterAbramsonCancerCenterheUniversityofPennsylvaniaMikhailRoshal,MD,PhD≠MemorialSloanKetteringCancerCenterSophieSong,MD,PhD≠UCLAJonssonComprehensiveCancerCenterJoannaWeinstein,MD€RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversitySaraZarnegar-Lumley,MD,MS€Vanderbilt-IngramCancerCentercMillianMSξBonemarrowtransplantationфDiagnosticradiology‡Hematology/HematologyoncologyÞInternalmedicine≠Pathology€Pediatriconcology*DiscussionWritingCommitteeMemberVersion2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexlievesthatthebestmanagementforanypatientlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.aryoftheGuidelinesUpdates•Diagnosis(PBCL-1)•AdditionalDiagnosticTesting(PBCL-2)•Workup(PBCL-3)•RiskGroupDefinitions(PBCL-4)•Staging(PBCL-5)eLargeBcellLymphomaBCLtinalLargeBCellLymphoma•PrinciplesofDiagnosticPathology(PBCL-A)•PrinciplesofSystemicTherapy(PBCL-B)•ResponseCriteria(PBCL-C)•PrinciplesofSupportiveCare(PBCL-D)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2022.Version2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexGuidelinesforPediatricAggressiveMatureBCellLymphomasfromVersionincludeGeneralChanges•NewsectionswereaddedforthediagnosisandmanagementofprimarymediastinallargeB-celllymphoma(PMBL).ABBR1reviationsGuidelinesforPediatricAggressiveMatureBCellLymphomasfromVersioninclude•Titlecombined:DiagnosisofPediatricAggressiveMatureB-CellLymphomas•Diagnosisrevised:PediatricBurkittlymphoma(BL)andPediatricdiffuselargeB-celllymphoma,nototherwisespecified(DLBCL,NOS)includingadolescentandyoungadult(AYA)patientstreatedinthepediatriconcologysetting•Footnotefrevised:SeePrinciplesofDiagnosticPathology(PBCL-A)•AdditionalDiagnosticTesting:EssentialpBullet2movedfromsub-bullettobullet:Fluorescenceinsituhybridization(FISH):C-MYCrearrangement•Workup:EssentialpBullet6;sub-bullet7revised:Considerglucose-6-phosphatedehydrogenase(G6PD)testingformalepatients•Workup:UsefulUnderCertainCircumstancesp5thBulletadded:ConsiderbaselineIgpanel,ifuseofrituximabiscontemplated•RiskGroupDefinitionspTherapyHeaderRevised:InductionTherapy/InitialTreatmentInitialTherapypGroupClassification◊GroupBremoved:AllcasesnoteligibleforGroupAorGroupC(unresectedstageIandnon-abdominalstageII,stageIII,andnon-CNSstageIVwith<25%bonemarrowinvolvement)◊GroupB(Lowrisk)added:UnresectedstageIandnon-abdominalstageIIorstageIIIwithlowLDH(≤2timestheupperlimitofnormal[ULN])◊GroupB(Highrisk)added:StageIIIwithhighLDH(>2timesULN,andallnon-centralnervoussystem(CNS)stageIVwithbonemarrowinvolvement(<25%lymphomacells)•Footnoteqadded:Minard-ColinV,AupérinA,PillonM,etal.Rituximabforhigh-risk,matureB-cellnon-Hodgkin'slymphomainchildren.NEnglJMed2020;382:2207-2219.•Footnotexrevised:Reassesssitesoforiginaldiseasewithradiologicimagingstudiesasindicated.(SeePBCL-3)(AlsoonPBCL-6)•Footnoteaarevised:Residualmassshouldbebiopsiedpriortocategorizingitasresidualdisease.Repeatbiopsyofresidualmassshouldbeconsideredpriortoadditionaltherapy.(AlsoonPBCL-6,PBCL-7,andPBCL-8)•Footnoteremoved:TheBerlin-Frankfurt-Münster(BFM)grouphasequivalentregimensthatarenotstandardlyusedinNorthAmerica.(AlsoonPBCL-6,PBCL-7,andPBCL-8)•Footnoteremoved:RadiationtherapyrarelyhasaroleinpediatricaggressivematureB-celllymphomasduetotherapidlysisoftumortochemotherapyandtheavoidanceoflong-termsideeffectsinchildren.(AlsoonPBCL-6,PBCL-7,andPBCLPrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexGuidelinesforPediatricAggressiveMatureBCellLymphomasfromVersionincludepAfterGroupB(lowrisk),Toppathwayrevised:UnresectedStageIandornon-abdominalStageII•Footnoteremoved:AnyStageIIIpatientwithLDH≤2timestheupperlimitofnormal(ULN),andallStageIorIIpatientswhoarenotfullyresectedGroupA.•Footnoteremoved:HighLDH:>2timestheULN.LowLDH:≤2timestheULN.•Footnoteremoved:AnyStageIIIpatientwithLDH>2timesULN,andallnon-CNSStageIVpatientswith<25%bonemarrowinvolvement.•Footnoteggrevised:Reassesssitesoforiginaldiseasewithradiologicimagingstudiesasindicated(SeePCBL-3).BonemarrowandCSFstudiesshouldalsobeperformedifbonemarroworCSFwereinitiallyinvolved.(AlsoonPBCL-8)•Footnoteiirevised:ForpatientsonregimenC1therapywithlessthan20%responsetothereductionphase,continueregimenC1therapyorchangetoregimenC3therapy.•Headingrevised:DiseaseSurveillance/Follow-uppBullet3revised:UltrasoundofabdominaltumorsAbdominalultrasoundpBullet4,sub-bulletrevised:FDG-PET/CTorFDG-PET/MRIorCTchestwithIVcontrastandCTabdominal/pelviswithIVandoralcontrast.ConsiderFDG-PET/CTorFDGPET/MRIifrelapseissuspectedbasedonCTscanfindings.•Footnotejjrevised:pathologicconfirmationofrelapseisrecommendedbeforestartingrelapsetherapyforrelapseddisease,andrestagingworkupshouldbecompletedasforinitialdiagnosis.PBCL-A(1of3)•Headingrevised:PrinciplesofDiagnosticPathology(AlsoonPBCL-A2of3andPBCL-A3of3)pSub-headingrevised:Diagnosis-MorphologypSub-headingrevised:Diagnosis-ImmunophenotypingUPDATESVersion2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexGuidelinesforPediatricAggressiveMatureBCellLymphomasfromVersionincludePBCL-A(2of3)•Sub-headingrevised:Diagnosis-CytogeneticsandMolecularStudiespBullet1,sub-bullet5revised:...high-gradeB-celllymphoma(“double”or“triplehit”),IGH/BCL2andBCL6rearrangementpstatusmaybeinterrogatedbyFISHlymphomas(HGBLs)withtranslocationsofMYCandBCL2and/orBCL6rearrangements,IGH/BCL2andBCL6rearrangementstatusmaybeinterrogatedbyFISH.asdetectedbyFISHorstandardcytogenetics("double-hit"or"triple-hit").Atpresent,high-gradeB-celllymphomaHGBCListhoughttobeuncommon..Pediatrichigh-gradeB-celllymphomaHGBCListreatedwiththesameregimenaspediatricBL.SeetheNCCNGuidelinesforB-CellLymphomasforafulldiscussiononhighgradeB-celllymphomasHGBCL.PBCL-B(2of10)•PreferredRegimensforGroupBpBullet1revised:POG9219Regimen(asforGroupAonPBCL-B1of10)–OnlyforUnresectedStageIand/orNonabdominalStageII,normalLDHPBCL-B(4of10)•PreferredRegimensforGroupCpCOGANHL1131(basedonFAB/LMB96withomissionofM3andM4cycles)RegimenC1◊RegimenC1/Pre-phaseCOP:Leucovorindoseandscheduleremovedfromthetable.PBCL-B(9of10)•Footnoteaadded:RadiationtherapyrarelyhasaroleinpediatricaggressivematureB-celllymphomas.(AlsoforallotherappropriatePBCL-Bpages)•Footnotecrevised:AlargebodyofmaturedatashowsthattheBFMregimensareassafeandefficaciousasthePOG,FAB/LMB,andCOGregimens.However,theyarenotstandardlyroutinelyusedinNorthAmerica.PBCL-B(10of10)•Headingrevised:PreferredRegimensforInitial/InductionTherapy•Footnoteremoved:IntergroupRandomizedTrialforChildrenorAdolescentsWithB-CellNonHodgkinLymphomaorB-AcuteLeukemia:RituximabEvaluationinHighRiskPatients.GustaveRoussy,CancerCampus,GrandParis;Children'sOncologyGroup;2017.PBCL-D(1of5)PrinciplesofSupportiveCare•TumorLysisSyndromepBullet2revised:TLScanbeasymptomaticbutorcancauseseizures,cardiacarrhythmias,acuterenalfailure,neuromuscularabnormalities,hypotensionand/ordeathPBCL-D(3of5)•Headingrevised:FollowingInitiationofSystemicTherapyChemotherapypBullet1revised:Abdominalpain,bowelobstruction,andbowelperforationhavebeendescribedinpatientstreatedwithrituximab.Thesesymptomsshouldpromptearlydiagnosticevaluationtoincludeplainfilmsand/orCToftheabdomenandpelvis.PBCL-D(4of5)•Headingrevised:SupportiveCareRelatedtoSystemicTherapytheChemotherapyPrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexSde•BiopsypExcisionalorincisionalbiopsyofmostaccessiblesiteispreferred.pTouchpreparationsoffreshlesionaltissueshouldbeencouragedwheneverpossiblesince,ifdoneproperly,theymayrevealessentialcytologicdetailsthatmaybedifficulttodetectinsmallbiopsies(eg,smallneedlecorebiopsy).pAcoreneedlebiopsyislessoptimalbutcanbeusedincircumstanceswhenalymphnodeortumormassisnoteasilyaccessibleforexcisionalorincisionalbiopsy.pCoresmustbeofsufficientsizeandnumbertoallowforevaluationofmorphology,tumorarchitecture,andallnecessaryancillarystudies(immunohistochemistry[IHC],flowcytometry,karyotype,andfluorescenceinsituhybridization(FISH)formajortranslocations,asapplicable).pAfine-needleaspiration(FNA)biopsyaloneisnotsuitablefortheinitialdiagnosisofpediatriclymphoma.pPlacefreshspecimeninsaline,notformalin,ensuringviablediagnostictissueforlogyclogyc•Burkittlymphoma(BL)•DiffuselargeB-celllymphoma,nototherwisespecified(DLBCL,NOS)•PrimarymediastinallargeB-celllymphoma(PMBL)AdditionalosticCLaThePediatricAggressiveMatureB-CellLymphomaspanelconsiders“pediatric”toincludeanypatientaged18yearsandyounger,andAYApatientsolderthan18yearsofage,whoaretreatedinapediatriconcologysetting.PracticepatternsvarywithregardstoAYApatientsfromcentertocenterintermsofwhetherAYApatients(definedbytheNationalCancerInstituteas<39yearsofage)withmatureB-celllymphomaaretreatedprimarilybypediatricoradultoncologists.TheseguidelinesareintendedtoapplytoAYApatientswithgoodorganfunctiontreatedinapediatriconcologysetting.AYApatientstreatedinanadultoncologysettingshouldbetreatedaspertheadultNCCNGuidelinesforB-CellLymphomas.bAlsoseetheNCCNGuidelinesforAdolescentandYoungAdult(AYA)Oncology.cPrinciplesofDiagnosticPathology(PBCLSee-A).dPediatricBLandDLBCLarecurable,butmanagementiscomplex.Itispreferredthattreatmentoccuratcenterswithexpertiseinthemanagementofthesediseases.ePMBLcanbedefinedasaclinicalentitypresentingwithprimarysiteofdiseaseintheanteriormediastinumwithorwithoutothersitesandhistologyofDLBCL.PMBLoverlapswithmediastinalgreyzonelymphomasthathavefeaturesintermediatebetweenPMBLandclassicHodgkinlymphoma,andhaveuniquediagnosticcharacteristics.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PBCL-1orsinglenucleotidepolymorphismSNParrayforqaberrationSHkMYCIHCPrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.NotapprovedfororsinglenucleotidepolymorphismSNParrayforqaberrationSHkMYCIHCNCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexADDITIONALDIAGNOSTICTESTINGcESSENTIAL•Adequateimmunophenotypingtoestablishdiagnosisf,g,hpIHCpanel:Ki-67,BCL2,BCL6,CD3,CD10,CD20,MUM1pFlowcytometry:Surfacekappa/lambda,CD3,CD5,CD10,CD19,CD20,CD45pIHCpanelforPMBL:CD10,CD19,CD20,PAX5,CD23,CD30,BCL2,BCL6,MUM1,andKi-67;EBVisabsentpFlowcytometrypanelforPMBL:Surfacekappa/lambda,CD3,CD5,CD10,CD19,CD20,CD22,•FISH:MYCrearrangementi•FISH:MYCrearrangementipFISHforBCLandBCLrearrangementsjKaryotypet14)orvariantsFISHforBCLandBCLrearrangementsj•TdTIHCorflowcytometry•Clonalitytestingbypolymerasechainreaction(PCR)forimmunoglobulingenerearrangementcPrinciplesofDiagnosticPathology(PBCLSee-A).fTypicalimmunophenotypeofBL:sIg+,CD10+,CD20+,TdT-,Ki-67+(≥95%),BCL2-,BCL6+,simplekaryotypewithMYCrearrangementassoleabnormality.TypicalimmunophenotypeofDLBCL:sIg+,CD20+,TdT-,Ki-67variablyhigh,CD10+/-,BCL6+/-,MUM1+/-,BCL2+/-,variablekaryotypewithMYC,BCL6,BCL2,and/orotherIGHrearrangements.gTypicalimmunophenotypeofPMBL:sIg-,B-cellantigens+(CD19+,CD20+,CD79a+,andPAX5+),CD23+,CD30+,MUM1+,BCL2+/-,andBCL6+/-.EBV-EBERisnegative.SeeUseofImmunophenotyping/GeneticTestinginDifferentialDiagnosisofMatureB-CellandNK/T-CellNeoplasms(NHODG-A)intheNCCNGuidelinesforB-CellLymphomas.hIfflowcytometryisinitiallyperformed,IHCforselectedmarkers(BCL2andKi-67)cansupplementtheflowresults.iOnformalin-fixed,paraffin-embeddedtissue,MYCrearrangementisbestassessedbyMYCbreakapartprobetocaptureanypartnergene.jDouble-andtriple-hitlymphomasarecurrentlynotwelldescribedorstudiedinthepediatricpopulationbutFISHforBCL2andBCL6rearrangementsmaybeconsideredintheAYApopulation.kEBER-ISHismostapplicableinendemicBLorimmunocompromisedclinicalsettingsforeitherBLorDLBCL.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PBCL-2arrowo•Considerbaselineimmunoglobulinpanel,ifuseofontemplatedelvishandwithoutBLorDLBCLarrowo•Considerbaselineimmunoglobulinpanel,ifuseofontemplatedelvishandwithoutBLorDLBCLdIVcontrastRIwithandwithoutcontrastdelaytreatmenttoobtain)mNCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexWORKUPdging•History,includingpersonalandfamilyhistoryofimmunodeficiency•Physicalexamination,withattentiontolymphnodes,Waldeyer’sring,liverandspleensize,effusions,ascites,neurologicsigns•Evaluationforsignsorsymptomsofureteralorbowelobstruction•Evaluationforsignsorsymptomsofspinalcordcompressionorcranialneuropathy•Performancestatus(Lansky/Karnofsky)•LabsabdominalultrasoundifabdominalultrasoundifcrosssectionalimagingnotlepElectrolytes,calcium,phosphorus,bloodureale•Echocardiogram(ECHO)ormultigated•Echocardiogram(ECHO)ormultigatedacquisition(MUGA)scanandECG•Fertilitycounselingrecommended;fertilitypreservationasclinicallyappropriateSeeNCCNGuidelinesforAdolescentandYoungAdult(AYA)OncologypLactatedehydrogenase(LDH)pAspartatetransaminase(AST),alaninetransaminase(ALT),bilirubin,albuminpHepatitisBtesting(HBcAb,HBsAb,HBsAg)pConsiderformalepatientslpConsiderglucose-6-phosphatedehydrogenase(GformalepatientslUSEFULUNDERCERTAINCIRCUMSTANCES•MRIofthehead,ifclinically•MRIofthehead,ifclinicallyindicated•MRIofthespine,ifclinicallyindicated•Flowcytometryofcerebrospinalfluid(CSF)n•Flowcytometry,FISHforMYCrearrangement,andIHCnFlowcytometryofCSFsamplesisnotroutinelyrecommended,•LumbarpuncturepCellcountanddifferentialpCytology,includingtotalnucleatedcellcountandmorphologicreviewofcytospinefullSeePrinciplesofSupportiveCare(PBCLefulatthepathologist'sdiscretion.oForlow-levelormorphologicallyindeterminateinvolvement.mObtainingaPETatthepathologist'sdiscretion.oForlow-levelormorphologicallyindeterminateinvolvement.qualityhigh-resolutionCTorMRI.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PBCL-3Version2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexONSGroupClassification(SeePBCL-5forStaging)InductionTherapy/InitialTreatmentCompletelyresectedstageIorCompletelyresectedabdominalstageIICLUnresectedstageIandnonabdominalstageIIorstageIIIwithlowLDH2timestheupperlimitofnormal[ULN])CLGroupBGroupBStageIIIwithhighLDHtimesULN),orallnon-centralnervoussystem(CNS)stageIVwithbonemarrowinvolvement(<25%lymphomacells)CLGroupCqAnyCNSinvolvementrand/orBonemarrowinvolvement(≥25%lymphomacells)CLprinAPillonMetalRituximabforhighriskmatureBcellnonHodgkinslymphomainchildrenNEnglJMed2020;382:2207-2219.qCairoMS,GerrardM,SpostoR,etal.Resultsofarandomizedinternationalstudyofhigh-riskcentralnervoussystemBnon-HodgkinlymphomaandBacutelymphoblasticleukemiainchildrenandadolescents.Blood2007;109,2736-2743.rTheCNSisconsideredinvolvedifoneormoreofthefollowingapplies:•AnylymphomacellsbycytologyinCSF•AnyCNStumormassbyimaging•Cranialnervepalsy(ifnotexplainedbyextracranialtumor)•Clinicalspinalcordcompression•Parameningealextension:cranialand/orspinalNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PBCL-4Version2.2022,09/12/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon10/4/20227:02:21AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022PediatricAggressiveMatureB-CellLymphomasdexSTAGINGInternationalPediatricNon-HodgkinLymphomaStagingSystems,tStageIAsingletumornotinthemediastinumandabdomenStageII•Asingleextranodaltumorwithregionalnodeinvolvement•Twoormorenodalareasonthesamesideofthediaphragm•Aprimarygastrointestinaltracttumor(usuallyintheileocecalarea),withorwithoutinvolvementofassociatedmesentericnodes,thatiscompletelyresectable(ifascitesorextensionofthetumortoadjacentorgans,itshouldberegardedasstageIII)ageIII•Twoormoreextranodaltumors(includingboneorskin)•