系统性肥大细胞增多症2021v3-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)SystemicMastocytosisrsionJulyVersion3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon9/2/202110:20:53AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2021NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.tocytosisdex*AaronT.Gerds,MD,MS/Chair‡†ÞCaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitute*JasonGotlib,MD,MS/Vice-Chair‡StanfordCancerInstituteHarisAli,MD‡ξCityofHopeNationalMedicalCenterPrithvirajBose,MD‡TheUniversityofTexasMarianaCastells,MD,PhDÞσ/AdjunctPanelMemberDana-Farber/BrighamandWomen’senterMichaelW.Deininger,MD,PhD‡HuntsmanCancerInstituteattheUniversityofUtahAndrewDunbar,MD†MemorialSloanKetteringCancerCenterAmroElshoury,MD‡RoswellParkComprehensiveCancerCenterTracyI.George,MD≠HuntsmanCancerInstituteattheUniversityofUtahKrishnaGundabolu,MBBS‡Fred&PamelaBuffettCancerCenterElizabethHexner,MD‡ξAbramsonCancerCenterheUniversityofPennsylvaniaGabrielaS.Hobbs,MD‡MassachusettsGeneralHospitalCancerCenterTaniaJain,MBBS†TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsCatrionaJamieson,MD,PhD‡UCSanDiegoMooresCancerCenterAndrewT.Kuykendall,MD‡ÞMoffittCancerCenterYazanMadanat,MD‡UTSouthwesternSimmonsComprehensiveCancerCenterBrandonMcMahon,MD‡UniversityofColoradoCancerCenterSanjayR.Mohan,MD‡Vanderbilt-IngramCancerCenterStephenOh,MD,PhD‡SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineAnimeshPardanani,MBBS,PhD‡MayoClinicCancerCenterNikolaiPodoltsev,MD,PhD‡YaleCancerCenter/SmilowCancerHospitalErikRanheim,MD,PhD≠UniversityofWisconsineCancerCenteresPanelDisclosuresLindsayRein,MD‡DukeCancerInstituteRachelSalit,MD‡FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceBradyL.Stein,MD,MHS‡ÞRobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityMosheTalpaz,MD†UniversityofMichiganRogelCancerCenterPankitVachhani,MD‡O'NealComprehensiveCancerCenteratUABMarthaWadleigh,MD‡†Dana-Farber/BrighamandWomen’senterKatherineWalsh,MD†‡TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteDawnC.Ward,MD≠UCLAJonssonComprehensiveCancerCentererPhDQAllergy/Immunology‡Hematology/HematologyoncologyÞInternalmedicine†Medicaloncology≠PathologyξTransplantation*DiscussionWritingCommitteeMemberVersion3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.astocytosisPanelMembersyofGuidelinesUpdates•DiagnosticAlgorithm(SM-1)•Workup(SM-2)•TreatmentforIndolentSystemicMastocytosis(ISM)andSmolderingastocytosisPanelMembersyofGuidelinesUpdates•DiagnosticAlgorithm(SM-1)•Workup(SM-2)•TreatmentforIndolentSystemicMastocytosis(ISM)andSmolderingSystemicMastocytosis(SSM)(SM-3andSM-4)•TreatmentforAggressiveSystemicMastocytosis(ASM)(SM-5)•TreatmentforSystemicMastocytosiswithanAssociatedHematologicNeoplasm(SM-AHN)(SM-6andSM-7)•TreatmentforMastCellLeukemia(SM-8)•2017WorldHealthOrganization(WHO)ClassificationofMastocytosis(SM-A)•2017WHODiagnosticCriteriaforCutaneousandSystemicMastocytosis(SM-B)•2017DiagnosticCriteriafortheVariantsofSystemicMastocytosis(SM-C)•WHOCriteriaforB-FindingsandC-Findings(SM-D)•IWG-MRT-ECNMCriteriaforEligibleOrganDamagetoAssessClinicalImprovementandTreatmentResponse(SM-E)•RecommendationsforHistopathologyAnalysisandKITD816VMutationTesting(SM-G)•AdversePrognosticVariablesandRiskStratificationinSystemicMastocytosis(SM-H)•SignsandSymptomsofMastCellActivationandPotentialTriggersofMastCellActivation(SM-I)•Anti-MediatorDrugTherapyforMastCellActivationSymptoms(SM-J)•SpecialConsiderationsfortheManagementofPatientswithSystemicMastocytosis(SM-K)•ManagementofMidostaurinToxicity(SM-L)•ManagementofAvapritinibToxicity(SM-M)tocytosisdexedNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2021.Version3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.fferentiatedSMWDSMmnupperpathway•MonitorforprogressionofAHNandSMcomponentFifthcolumn,lowerpathway:•MonitorforprogressionofAHNandSMcomponentFootnotefferentiatedSMWDSMmnupperpathway•MonitorforprogressionofAHNandSMcomponentFifthcolumn,lowerpathway:•MonitorforprogressionofAHNandSMcomponentFootnote•"u"isnewtothepage:ThesealgorithmsrefertoSM-AHNwithmyeloidAHNsaremyeloidneoplasms...SM-Bbmodifiedtoincludethefollowing:NormalmastcellmarkersincludeaseisthemostspecificmarkerofmastcellsloneisnotsufficienttoestablishmastcelllineageUPDATEStocytosisdexsionoftheNCCNGuidelinesforSystemicMastocytosisfromVersioninclude•Avapritinib(ifplatelets≥50x109/L)isapreferredregimenforaggressivesystemicmastocytosis(ASM)withthefollowingfootnote:AvapritinibisnotrecommendedforthetreatmentofpatientswithadvancedSMwithplateletcountsoflessthan50x109/L.Forthemanagementofavapritinibtoxicity,seeSM-M.(AlsoforSM-7[SM-AHN],SM-8[MastCellLeukemia]).SM-K,2of4•Bullet6underPregnancy,addedavapritinibtothe2ndsentence.SM-M•ManagementofAvapritinibToxicityisanewpage.MS-1•TheDiscussionhasbeenupdatedtoreflectthechangestothealgorithm.sionoftheNCCNGuidelinesforSystemicMastocytosisfromVersioninclude•Discussionsectionhasbeenupdatedtoreflectthechangesinthealgorithm.SM-ChmastcellsinbonemarrowaspirateisreferredtoasASMintransformationASMtUpdatesinVersion1.2021oftheNCCNGuidelinesforSystemicMastocytosisfromVersion1.2020include:eosinophiliaispresenteosinophiliaispresentthenscreenforFIPLPDGFRAfusiongene.ThirdcolumnThirdcolumnUsefulinCertainCircumstances,modified:•Biopsyprovenadult-onsetMIS.•ImatinibonlyifforKITD816Vmutationnegative•ImatinibonlyifforKITD816Vmutationnegativeorunknown;orifWell-•..andKITD816Visnegative•Newcolumnheadersadded:pThirdcolumn:DiagnosticCriteriapFourthcolumn:Diagnosis•Fifthcolumn:±Hereditaryalpha-tryptasemia(HαT)Footnotesneoplasms,whichcomprisethemajorityofcases.cmodifiedfirstsentence:Theoverwhelmingmajority(about90%)ofneoplasms,whichcomprisethemajorityofcases.cmodifiedfirstsentence:Theoverwhelmingmajority(about90%)ofinpatientswithSM,especiallyindolentorsmolderingSM(ISM/SSM).Itmayalsobefoundwithcutaneousmastocytosis.HαTisassociatedwithanincreasedriskofseveremediatorsymptoms/anaphylaxis.References:•GreinerG,etal.Blood2021;137:238–247andLyonsJJ,etal.JAllergyClinImmunol2021;147:622-632arenewtofootnote"f."•Updated:PardananiA.AmJHematol2019;94:363-377.Sixthbullet,modified:•Cytogeneticsisnowasub-bulletunderBonemarrowaspirateandbiopsyEighthbullet,modified:•MoleculartestingforKITD816Vusinganassaywithhighsensitivity(eg,allele-specificoligonucleotidequantitativereversetranscriptasePCR[ASO-qPCR]ordigitaldropletPCR).IfnegativeforKITD816VmutationandVersion3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.SM>ISM/SSM,particularlyinareasofmastcellaggregates.Ninthbulletsecondsentencemodified:MyeloidmutationpanelsmmendedforthedetectionofKITDVNextgenerationsequencingNGSassayscanexhibitSM>ISM/SSM,particularlyinareasofmastcellaggregates.Ninthbulletsecondsentencemodified:MyeloidmutationpanelsmmendedforthedetectionofKITDVNextgenerationsequencingNGSassayscanexhibitlowsensitivityandhighersensitivityassaysshouldalwaysbeperformedshouldformedonthebonemarrowbutcanbeperformedontheralbloodinthepresenceofanAHNandorcirculatingmastcellsMyeloidmutationpanelsarenotrecommendedfortheofKITDVofapproximatelygsThirdbulletmodified:Skeletalinvolvement,withlargeosteolyticlesionsifthesizeofthelesioniscmitisconsideredlarge)withorwithoutpathologicfractures(pathologicfracturescausedbyosteoporosisdonotqualifyasaC-finding).Smallosteolyticand/orscleroticlesionsdonotdefineadvancedSM.SM-F(2of2)"§"Fifthsentencemodifiedtoinclude"ormastcellleukemia"SMGof3)Firstbullet,modified:Reviewofthebonemarroworotherextracutaneousorgansforinvolvementbyneoplasticmastcellsshouldbeundertakenbyahematopathologistand/orcenterwithexpertiseinthepathologyofmastcelldiseases.managementofpatientswithmastcelldiseases.ThirdbulletmodifiedBonemarrowaspirateandbiopsy...mastcellsWell-differentiatedSMisamorphologicvariantpresentinallsubtypesofSM.ASMintransformation(ASM-t).correspondingfootnoteIntheabsenceofahighlysensitivetocytosisdexsionoftheNCCNGuidelinesforSystemicMastocytosisfromVersionincludeSM-C•SignificanteditsmadetoMastcellleukemia.FootnoteASMwith≥5%mastcellsinbonemarrowaspirateisreferredASMwith≥5%mastcellsinbonemarrowaspirateisreferredtoasFirstFirstbulletdeletedandbefore(focal,denseaggregates)Sixthbulletmodified...whichisrelativelycommoninadvancedFourthbulletmodifiedBonemarrowcorebiopsy(1–2cm)...percentmastcellburdenandmorphologyofmastcellsinbiopsy(eg,multifocaldenseinfiltratesSixthbulletmodified...whichisrelativelycommoninadvancedSMGof3)thhighsensitivitywithSMGof3)thhighsensitivitywiththefollowingquantitativePCRassay,qualitativePCRcanbeused.•Secondbullet,secondandthirdsentencesarenew:Freshbonemarrowaspirateispreferable,butformalin-fixedparaffin-embeddedtissuecanalsobeused.DecalcifiedtissuetypicallyinterfereswithDNA/RNAassays,andthus,decalcifiedBMshouldnotbeusedformutationalanalysis.IfinitialscreeningoftheperipheralbloodfailstodetecttheKITD816VmutationinapatientwithsuspectedSM,testingofthebonemarrowshouldbeundertakenwithahighlysensitiveassay(eg,ASO-qPCRordigitaldropletPCR).•Fourthbullet,#3,modified:Patientsarepositiveforothermutationsatcodon816(D816H,D816Y,others)orinotherregionsofKITthatarenotdetectablebyhigh-sensitivityassays(eg,ASO-qPCRordigitaldropletPCR).•Fifthbullet,modifiedtoinclude:(eg,ASO-qPCRordigitaldropletPCR)•Eighthbullet,modifiedtoinclude:byhigh-sensitivityassays(eg,ASO-qPCRordigitaldropletPCR)SM-G(3of3)•Thefollowingreferenceisnew:GreinerG,GurbiszM,RatzingerF,etal.DigitalPCR:AsensitiveandprecisemethodforKITD816Vquantificationinmastocytosis.ClinChem2018;64:547-555.SM-H(5of5)•GlobalPrognosticScoreModel(GPSM)forpredictingPFSandOSinpatientswithSystemicMastocytosisarenewtables,withthefollowingcorrespondingreference:Muñoz-GonzálezJI,Ǻlvarez-TwoseI,Jara-AcevedoM,etal.Proposedglobalprognosticscoreforsystemicmastocytosis:aretrospectiveprognosticmodellingstudy.2021;8:e194-e204.ectedmastcellstocytosisintheskinimmunohistochemistrye•ScreenforFIP1L1-PDGFRAifeosinophiliaispresentandKITD816VisnegativeSM-1PrintedbyMinTangon9/2/202110:20:53AM.Forpersonaluseonly.Notapprovedforectedmastcellstocytosisintheskinimmunohistochemistrye•ScreenforFIP1L1-PDGFRAifeosinophiliaispresentandKITD816VisnegativeSM-1tocytosisdexDIAGNOSTICALGORITHMFORTHEPATIENTPRESENTINGWITHSIGNSORSYMPTOMSOFMASTOCYTOSISastcellactivationsyndromeMMASalsoreferredCRITERIAsyndrome[MCAS])giderothercausessyndrome[MCAS])giderothercausesforactivationsymptomsboranaphylaxis,and/orincreasedserumtryptase[MIS],B-orC-findings,dorabnormalbloodcounts)provenadultonsetMISEvaluationforsystemicmastocytosis(SM)•Bonemarrowbiopsyorbiopsyoforganwithsuspectedextracutaneousinvolvement•MoleculartestingforKITD816V(SeeSM-2);ifneeded,additionalKITgenesequencing•Mastcellimmunophenotypingusingflowcytometryand/ortoasprimarymastcelltoasprimarymastcellactivationand/orCD25+mastcells)allactivationegsecondaryMCAS)gllactivationegsecondaryMCAS)greditarygiesdrugsconnectiveyptasemiatissuedisordersinfections)elleASanaphylaxisgcASanaphylaxisgcmastocytosisSMCutaneousmastocytosisa,h1minoror≥3minorcriteriaaaThediagnosisofmastocytosisaThediagnosisofmastocytosisanditssubtypesisbasedonthe2017WHOCriteriaedandImmunohistochemistrymarkersincludeCD117,CD25,andtryptase.Forbothtechniques,CDImmunohistochemistrymarkersincludeCD117,CD25,andtryptase.Forbothtechniques,CD30isoptional.AlsoseeSM-2.fHαTisamultisystemdisordercharacterizedbyduplicationsandtriplicationsintheTPSAB1geneencodinga-tryptaseassociatedwithelevationofthebasalserumtryptaselevelandsymptomsincludingcutaneousflushingandpruritus,dysautonomia,functionalgastrointestinalsymptoms,chronicpain,andconnectivetissueabnormalities,includingjointhypermobility.(LyonsJJ,etal.NatGenet2016;48:1564-1569).HαTmaybediagnosedalone,butisalsoenrichedinpatientswithSM,especiallyindolentorsmolderingSM(ISM/SSM).Itmayalsobefoundinpatientswithcutaneousmastocytosis.HαTisassociatedwithanincreasedriskofseveremediatorsymptoms/anaphylaxis.(GreinerG,etal.Blood2021;137:238-247andLyonsJJ,etal.JAllergyClinImmunol2021;147:622-632).cytogenetic/molecularanalyses.See2017WorldHealthOrganizationClassificationofMastocytosis(SM-A);see2017WHODiagnosticCriteriaforCutaneousandSystemicMastocytosis(SM-B);andsee2017DiagnosticCriteriafortheVariantsofSystemicMastocytosis(SM-C).bPatientsshouldbecounseledaboutthesigns/symptomsandpotentialtriggersofmastcellactivation(SeeSM-I).Multidisciplinarycollaborationwithsub-specialists(eg,anesthesiaforprocedures/surgery;high-riskobstetricsforpregnancy)isrecommended(SeeSM-K).cSerumtryptaselevelmaybe<20ng/mLoronlytransientlyelevated.dSeeWHOCriteriaforB-FindingsandC-FindingsinPatientswithSystemicMastocytosisgSpecificcriteriahavebeenestablishedforprimaryandsecondaryMCAS(AkinC.Mastcellactivationsyndromes.JgSpecificcriteriahavebeenestablishedforprimaryandsecondaryMCAS(AkinC.Mastcellactivationsyndromes.JAllergyClinImmunol2017;140:349-355).(SeeDiscussion).hManagementofcutaneousmastocytosisisnotincludedintheseguidelines.Referraltocenterswithexpertiseincutaneousmastocytosisisstronglyrecommended.Improvement(CI)andTreatmentResponse(SM-E).B-andC-findingsareusedforthediagnosisoftheWHOsubtypeofSM(SM-CandSM-D)andIWG-MRT-ECNMcriteriaareusedtoestablisheligibleorgandamagefindingsforclinicaltrialenrollmentandtoadjudicateresponsetotherapy(SM-E).eMastcellmarkersbyflowcytometryimmunophenotypingincludeCD117,CD25,andCD2.AdaptedfromPardananiA.Systemicmastocytosisinadults:2019updateondiagnosis,riskstratificationandmanagement.AmJHematol2019;94:363-377.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.FISHasneededforassociatedhematologicneoplasm(AHN)-relatedabnormalitiesjMoleculartestingforKITD816Vusinganassaywithhighsensitivity(eg,allele-specificoligonucleotidequantitativereversetranscriptasePCR[ASO-qPCR]ordigitaldropletPCR).j,k,lIfnegativeFISHasneededforassociatedhematologicneoplasm(AHN)-relatedabnormalitiesjMoleculartestingforKITD816Vusinganassaywithhighsensitivity(eg,allele-specificoligonucleotidequantitativereversetranscriptasePCR[ASO-qPCR]ordigitaldropletPCR).j,k,lIfnegativeforKITD816Vmutationandeosinophiliaispresent,thenscreenforFIP1L1-PDGFRAfusiongene.MyeloidmutationpanelegcontainingSRSFASXLRUNX1)j,k,lEvaluationofBandCFindingsandOrganInvolvementdCTMRIorultrasoundoftheabdomen/pelvisantoevaluateforosteopeniaosteoporosisMetastaticskeletalsurveytoevaluateforosteolyticlesionsdirectedbiopsyegendoscopyliverbiopsyasneededwithimmunohistochemistryeandCDasacontrolTcellmarkerAssessmentofsymptomburdenandqualityoflifeQOLusingtheMastocytosisSymptomAssessmentformMSAFandtheMastocytosisQualityofLifeQuestionnaire(MQLQ)mComprehensivemetabolicpanelwithuricacid,lactatedehydrogenase(LDH),andliverfunction(SM-3)and(SM-4)ndweightlosstocytosisdexWORKUPFORSUSPECTEDSYSTEMICMASTOCYTOSISiGeneralDiagnosticStudiesexaminationforMISspleenandliversizebypalpation;documentationofmedications,transfusionhistory,•H&P,includingexaminationforMISspleenandliversizebypalpation;documentationofmedications,transfusionhistory,erumtryptaselevelerumtryptaseleveldifferentialExaminationofbloodsmeareg,monocytosis,eosinophilia,dysplasia)jBonemarrowaspirateandbiopsywithj:pFlowcytometry:CD34,CD117,CD25,CD2;CD30(optional)pImmunohistochemistry:CD117,CD25,tryptase;CD30(optional)togenetics•24-hoururinestudiesforbiochemicalevidenceofmastHLAtestingifconsideringHLAtestingifconsideringallogeneichematopoieticcelltransplantHCT)CLASSIFICATIONiISMSmolderingSM(SSM)(SM-3)and(SM-4) matologicneoplasmSMAHNmatologicneoplasmSMAHN(SM-6)and(SM-7)astcellleukemiadSeeWHOCriteriaforB-FindingsandC-FindingsinPatientswithSystemicMastocytosis(SM-D)andIWG-MRT-ECNMCriteriaforEligibleOrganDamagetoAssessClinicalImprovement(CI)andTreatmentResponse(SM-E).B-andC-findingsareusedforthediagnosisoftheWHOsubtypeofSM(SM-CandSM-D)andIWG-MRT-ECNMcriteriaareusedtoestablisheligibleorgandamagefindingsforclinicaltrialenrollmentandtoadjudicateresponsetotherapy(SM-E).iSee2017DiagnosticCriteriafortheVariantsofSystemicMastocytosis(SM-C).jSeeRecommendationsforHistopathologyAnalysisandKITD816VMutationTestinginSystemicMastocytosis(SM-G1of3)and(SM-G2of3).kPreferredonthebonemarrow,asyieldfromtheperipheralbloodmaybelower;exceptionsmaybepatientswithSM-AHNorMCL.SeeSM-G2of3.lSeeAdversePrognosticVariablesandRiskStratificationinSystemicMastocytosis(SM-H).mvanAnrooijD,etal.Allergy2016;71:1585-1593.MSAFandMQLQhavebeenvalidatedonlyinpatientswithISM,notinpatientswithmoreadvancedformsofmastcelldisease.ToaccessthequestionnairesforMSAFandMQLQ,select"SupportingInformation"and"SeeAppendixS1andAppendixS2."Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.SM-2Version3.2021,07/09/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.B-indings)dPrintedbyMinTangon9/2/202110:20:53AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2021NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.B-indings)dtocytosisdexTREATMENTFORINDOLENTSYSTEMICMASTOCYTOSIS(ISM)ANDSMOLDERINGSYSTEMICMASTOCYTOSIS(SSM)lB-indings)dB-indings)detomsofdiseasebtomsofdiseasebidknowntriggersofmastcellactivationb•Carryinjectableepinephrine(2autoinjectors)tomanageanaphylaxis•AssesssymptomburdenandQOLusingMSAF•CounselpatientsregardingsignsandMQLQmtionssrecommended.•Referraltospecializedcenterstionssrecommended.stronglyAsymptomaticticmptomsofdiseasebselpatientsmptomsofdiseaseb•H&•H&P,labsannuallyorsoonerfornewclinicalissues•DEXAscanevery1–3yearsforpatientswithosteopenia/osteoporosis•AssesssymptomburdenandQOLusingMSAFandMQLQmonorClinicaltrialSymptomaticbPatientsshouldbecounseledaboutthesigns/symptomsandpotentialtriggersofmastcellactivation(SeeSM-I).Multidisciplinarycollaborationwithsub-specialists(eg,anesthesiaforprocedures/surgery;high-riskobstetricsforpregnancy)isrecommended(SeeSM-K).dSeeWHOCriteriaforB-FindingsandC-FindingsinPatientswithSystemicMastocytosis(SM-D)andIWG-MRT-ECNMCriteriaforEligibleOrganDamagetoAssessClinicalImprovement(CI)andTreatmentResponse(SM-E).B-andC-findingsareusedforthediagnosisoftheWHOsubtypeofSM(SM-CandSM-D)andIWG-MRT-ECNMcriteriaareusedtoestablisheligibleorgandamagefindingsforclinicaltrialenrollmentandtoadjudicateresponsetotherapy(SM-E).iSee2017DiagnosticCriteriafortheVariantsof