骨髓增生異常綜合癥2022.v3（英文）-NCCN腫瘤臨床實(shí)踐指南

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)MyelodysplasticSyndromesersionJanuaryNCCNGuidelinesforPatients?availableat/patientsVersion3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:18:48AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dex*PeterL.Greenberg,MD/Chair?TStanfordCancerInstitute*RichardM.Stone,MD/ViceChair??Dana-Farber/BrighamandWomen’senterArefAl-Kali,MD?MayoClinicCancerCenterJohnM.Bennett,MDT?≠UniversityofRochesterUmaBorate,MD?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteAndrewM.Brunner,MD??MassachusettsGeneralHospitalCancerCenterWanxingChai-Ho,MD?UCLAJonssonComprehensiveCancerCenterPeterCurtin,MD??CityofHopeNationalMedicalCenterCarlosM.deCastro,MD??DukeCancerInstituteH.JoachimDeeg,MD??FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceAmyE.DeZern,MD,MHS??TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsesPanelDisclosuresShiraDinner,MD??RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityCharlesFoucar,MD?UniversityofMichiganRogelCancerCenterKarinGaensler,MD?UCSFHelenDillerFamilyComprehensiveCancerCenterGuillermoGarcia-Manero,MD??TheUniversityofTexasElizabethA.Griffiths,MDT??RoswellParkComprehensiveCancerCenterDavidHead,MD≠Vanderbilt-IngramCancerCenterBrianA.Jonas,MD,PhD??UCDavisComprehensiveCancerCenterSiobanKeel,MD?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceYazanMadanat,MD?UTSouthwesternSimmonsComprehensiveCancerCenterLoriJ.Maness,MD?Fred&PamelaBuffettCancerCenterJamesMangan,MD?UCSanDiegoMooresCancerCenterShannonMcCurdy,MD?AbramsonCancerCenterattheUniversityofPennsylvaniaChristineMcMahon,MD?UniversityofColoradoCancerCenterBhumikaPatel,MD?CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstituteVishnuV.Reddy,MD≠?O'NealComprehensiveCancerCenteratUABDavidA.Sallman,MD??MoffittCancerCenterRoryShallis,MD?YaleCancerCenter/SmilowCancerHospitalPaulJ.Shami,MD?HuntsmanCancerInstituteattheUniversityofUtahSwapnaThota,MD?St.JudeChildren'sResearchHospital/TheUniversityofTennesseeHealthScienceCenterAsyaNinaVarshavsky-Yanovsky,MD,PhD?FoxChaseCancerCenterPeterWestervelt,MD,PhD??SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineerPhDerBSNRN?HematologyTInternalmedicine?Medicaloncology≠Pathology￥Patientadvocate*DiscussionsectionwritingcommitteeVersion3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.plasticSyndromesPanelMembersaryoftheGuidelinesUpdatesonMDSlassificationMDSManagementofLowerRiskDiseaseIPSSRplasticSyndromesPanelMembersaryoftheGuidelinesUpdatesonMDSlassificationMDSManagementofLowerRiskDiseaseIPSSRVeryLowLowIntermediateRiskDiseaseMDS)anagementofLowerRiskDiseaseIPSSRVeryLowLowIntermediateRiskDiseaseMDSnagementofHigherRiskDiseaseIPSSRIntermediateHighVeryHighRiskDiseaseMDSrtiveCareMDSWHOClassificationofMDSandMyelodysplastic/MyeloproliferativeOverlapNeoplasms,2017WHOficationandManagementMDSAoringSystemsMDSBsFrequentlySomaticallyMutatedinMDSMDSClialHighRiskAssessmentHereditaryMyeloidMalignancyPredispositionSyndromesMDSDsociatedWithHereditaryMyeloidMalignanciesMDSEmendationsforFlowCytometryMDSFdexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.ofPreferenceAllrecommendationsareconsideredappropriateSeeNCCNCategoriesofPreferenceTheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicalcircumstancestodetermineanypatientscareortreatment.TheNationalComprehensiveCancerNetwork?(NCCN?)makesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:18:48AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexsionoftheNCCNGuidelinesforMyelodysplasticSyndromesfromVersionincludeitialEvaluationpBullet12revised:...particularlyinpatientsyoungerthan4050yearsofage.MDS-7?SupportiveCarepRevisedsub-bullet:Transfusionproductsshouldbeirradiatedwith25Gyorperinstitutionstandard.pRevisedsub-bullet:Patientswith≥5%marrowblastswhoarecandidatesforreduced-intensityconditioning(RIC)shouldreceiveareencouragedtoreceive"debulking"therapywithHMAorinductionchemotherapy.MDS-B(2of3)?AddedlinksforWPSSrisks.Discussion?TheDiscussionwasupdatedtoreflectthechangesinthealgorithm.sionoftheNCCNGuidelinesforMyelodysplasticSyndromesfromVersioninclude?Modifiedfootnoteu,addedeltrombopag:Patientsgenerally≤60yandwith≤5%marrowblasts,orthosewithhypocellularmarrows,PNHclonepositivity,orSTAT-3mutantcytotoxicT-cellclones.ISTincludesequineATG±cyclosporinA±eltrombopag.Additionally,forseverethrombocytopenia,eltrombopagalonecouldbeconsidered.MDS-6AModifiedfootnotennSomeemergingdatahaveshownefficacyofnovelagents,includingvenetoclaxincombinationwithhypomethylatingagentsortargetedIDH1/2inhibitorsforcytoreductionforpatientswithhigh-riskMDS(DiNardoC,etal.NEnglJMed2018;378:2386-2398)hohaveHMArefractorydiseaseWhenusedascytoreductionforMDSincombinationwithHMAvenetoclaxhasbeeneffectivelygiveninmonthlycoursesofdaysGarciaJSetalASHAnnualMeeting020:Abstract656).shouldnotextendbeyond14days.Repeatofmarrowevaluationaftercyclesisimportantimperativetoclarifyensurerecoveryofhematopoiesisandpotentialrequirementforfurthertherapy.Clinicaltrialsarepreferred.(SeeDiscussion).Version3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESPrintedbyMinTangon3/14/20227:18:48AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexsionoftheNCCNGuidelinesforMyelodysplasticSyndromesfromVersionincludeitialEvaluationpBullet12revised:...particularlyinpatientsyoungerthan40patientsyearsoldofage.?FootnotesforInitialEvaluationofMDSpFootnoteerevised:...Functionallaboratorystudiesandconstitutional(germline)genetictestingusinglargenext-generationsequencing(NGS)panelstoincludegeneslistedonMDS-E,wholeexomeorwholegenomesequencingcomplementedwithinsilicocopynumbervariant(CNV)calling,and/orlaboratoryanalysisforCNVssuchasmicroarraytestingisrecommendedforpatientsshownonMDS-D5of5.canassistinthediagnosisofthesesyndromes...pFootnotefrevised:Inpatientsyoungerthan40patientsyearsoldofage,CSAisdueto...CSAmayappearlateduetolyonizationinX-linkedsideroblasticanemia(notlimitedtoyoungerpatientsandpatientsolderthan>60yearsoldofageatriskforgermlineDDX41andshorttelomeresyndromes).gpClassification?Classificationmovedtomiddlecolumnpathway.?PrgnosticCategory:IPSS-R:VeryLow,Low,Intermediate;IPSS:Low/Intermediate-1;WPSS:VeryLowLowIntermediate?ManagementofLower-RiskDisease(IPSS-RVery-Low-,Low-,IntermediateRiskDisease)pTitlechangedtotextnotedabove.pClinicallysignificantcytopenia(s)orincreasedmarrowblasts?Nodel(5q)+othercytogenicabnormalities:AddedSeeMDS-4.RemovedSerumEPO≤500mU/mL,SerumEPO>500mU/mL.pClinicallyrelevantthrombocytopeniaorneutropeniaorincreasedmarrowblasts?Otherrecommended,added:DecitabineorOraldecitabineandcedazuridine?Footnotetrevised:Oraldecitabineandcedazuridine(DEC-C)couldbeconsideredasasubstitutionforintravenousdecitabineinpatientswithIPSSIntermediate-1andabove.(AlsoforMDS-5A,MDS-6A)?PageorderofMDS-4andMDS-5hasbeenrevised.pFollow-up,Lowerpathway:withringsideroblasts≥15%(orringsideroblasts≥5%withanSF3B1mutation).Noresponse,luspatercept-aamt,seepathwayforSerumEPO>500mU/mL(poorprobabilitytorespondtoIST)(SeeMDS-5).pFollow-up,Lowerpathway:...withringsideroblasts≥15%(orringsideroblasts≥5%withanSF3B1mutation).Noresponse,considerlenalidomide,seepathwayforSerumEPO>500mU/mL(poorprobabilitytorespondtoIST)(SeeMDS-5)pFootnotezrevised:Exceptforpatientswithlowneutrophilcountsorlowplateletcounts.Recommendedinitialdoseis:10mg/dayfor21outof28daysor28daysmonthlyfor2–4monthstoassessresponse(SeeDiscussion).AlternativeoptiontolenalidomidemayincludeaninitialtrialofESAsinpatientswithserumEPO≤500mU/mL.Usecautionforpatientswithlowplateletandneutrophilcounts;(AlsoonMDS-5,MDS-5A)?PrognosticCategory:IPSS-R:VeryLow,Low,Intermediate;IPSS:Low/Intermediate-1;WPSS:VeryLow,LowIntermediate?ManagementofLower-RiskDisease(IPSS-RVery-Low-,Low-,Intermediate-RiskDisease)pTitlechangedtotextnotedabove.pSerumEPO≤500mU/mLpathway:Noresponseafter3mo6–8weeksorerythroidresponseNoresponseafter4mo6-8weekspSerumEPO?500mU/mLpathway:GoodprobabilitytorespondtoIST:?ATGor?ATG+cyclosporinAor?ATG+eltrombopag(category2B)or?ATG+cyclosporinA+eltrombopag(category2B)pSerumEPO?500mU/mLpathway:PoorprobabilitytorespondtoIST:?OtherRecommended,added:orOraldecitabineandcedazuridine?Noresponsewithin6cyclesofazacitidineor4cyclesofdecitabineororaldecitabineandcedazuridineorintolerance.?Footnotebbrevised:EncouragingdDataareemerginghavedemonstratedingtheeffectivenessofluspatercept...Forlower-riskMDSpatientslackingRStreatedwithluspatercept,encouragingalbeitlimiteddatahaveemerged(36%HI-Ein44patients)inabstractform[PlatzbeckerVersion3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATES?Sub-bullet1new:Transplantandnon-transplantpatientsshouldreceivesupport,?Sub-bullet2new:Transfusionproductsshouldbeirradiatedwith25Gy.?Sub-bullet3new:Patients?Sub-bullet1new:Transplantandnon-transplantpatientsshouldreceivesupport,?Sub-bullet2new:Transfusionproductsshouldbeirradiatedwith25Gy.?Sub-bullet3new:Patientswith≥5%marrowblastswhoarecandidatesforreduced-intensityconditioning(RIC)shouldreceive"debulking"therapywithHMAorinductionchemotherapy.Transplantationshouldbecarriedoutaslongaspatientsareresponding;itshouldnotbe?Sub-bullet1new:Patientsshouldreceiveantibioticprophylaxisatleastaslongastheyareonimmunosuppressivetherapy.?Sub-bullet2new:DetailedrecommendationsareprovidedintheGuidelinesgeneratedbytheAmericanSocietyofTransplantationandCellularTherapy(ASTCT,formerlyASBMT).SeeNCCNGuidelinesforMDSwhohaveHMA-refractorydisease(DiNardoC,etal.NEnglJMedClinicaltrialsarepreferred.(SeeDiscussion).(24%)...ContinueddexsionoftheNCCNGuidelinesforMyelodysplasticSyndromesfromVersioninclude?SupportiveCarepBullet1,Pre-Transplantnew:U,et?SupportiveCarepBullet1,Pre-Transplantnew:approvalhasnotyetoccurredforuseofthedrugforRSnegativepatients.Werecommendsuchpatientsenterclinicaltrialsforuseofluspatercept.?Footnoteddrevised:requirementby3to4months3to6monthsoftreatment.?Footnoteggrevised:...ISTincludesequineATG±cyclosporinA±eltrombopag(category2Bforeltrombopagcombinations).delayeduntiltheresponseislost.?CytokinespG-CSFsub-bulletdelayeduntiltheresponseislost.?CytokinespG-CSFsub-bullet1revised:G-CSFreferstothefollowingagent:filgrastim,filgrastim-sndz,andtbo-filgrastim...Intermediate-2,High;WPSS:High,Very-High(MDS-6)ManagementofHigher-RiskDisease(IPSS-RIntermediate-,High-,Very-High-RiskDisease)pTitlechangedtotextnotedabove.pTransplantcandidate,addedthefollowingtreatmentoptions:?Oraldecitabineandcedazuridinefollowedbyallo-HCT?Clinicaltrialfollowedbyallo-HCTp?OraldecitabineandcedazuridineasanoptionunderOtherRecommended.pRelapseafterallo-HCTorNoresponse?OraldecitabineandcedazuridineasanoptionunderOtherRecommendedpTheCategoriesofPreferencehavebeenappliedtothetreatmentregimensHematopoieticCellTransplantation.MDS-6ApFootnotessnew:AnFDA-approvedbiosimilarisanappropriatesubstitute?Footnotellrevised:AllogeneicHCTfromthemostsuitabledonor...Earlyforfilgrastim.NusedascytoreductionforMDS,shouldnotextendusedascytoreductionforMDS,shouldnotextendbeyond14days.Repeat?Referencesupdated.UPDATESVersion3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:18:48AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexionoftheNCCNGuidelinesforMyelodysplasticMDS-C(3of3)?Referencenew:LinderK,IragavarapuC,LiuD.SETBP1mutationsasabiomarkerformyelodysplasia/myeloproliferativeneoplasmoverlapsyndrome.BiomarkRes.2017;5:33.MDS-D(1of5)ticFamilialHighRiskAssessmentHereditaryMyeloidMalignancyPredispositionSyndromespBullet1revised:Patients...clonalhematopoiesis,oftenrarelyrespondpoorly...pBullet3revised:...germlineDDX41mutations.Patientsyoungerthan40yearsYoungerpatientswithMDS...MDS-D(2of5)eticFamilialHighRiskAssessmentHereditaryMyeloidMalignancyPredispositionSyndromespBullet1revised:...Consultationwithahereditary...below;pBullet5new:LimitationsoftheproposedapproachpBullet6new:SurveillanceMDS-D(4of5)ticFamilialHighRiskAssessmentHereditaryMyeloidMalignancyPredispositionSyndromespBullet5new:Limitationsoftheproposedapproach?Sub-bullet1new:ThecurrentcriteriaarefocusedmainlyonknowngeneticpredispositionsyndromestoMDSorAML.Theproposedagethresholdof50yearsatthetimeofdiagnosisisarbitraryandconditionsknowntobediagnosedatolderages(DDX41)withpredispositiontoMDSorAMLduetogermlinemaybemissed.Additionally,therearecertainlygeneticaberrationspredisposingtothedevelopmentofmyeloidneoplasmsthathavenotyetbeenidentifiedandassuch,somepatientsmaynotfittheaforementionedcriteria.Anyclinicalsuspicionofahereditaryconditionnotincludedintheseguidelinesmaystillwarrantareferraltoaninstitutionwithexpertiseinthefield.pBullet6new:Surveillance?Individualswhofulfilltheclinicaldiagnosticcriteriaforamyeloidneoplasmwithagermlinepredisposition,evenifthepathogenicgeneticvariantisundetermined.?Individualswithadeleteriousorlikelydeleteriousgeneticvariantassociatedwithagermlineredisposition,regardlessofclinicalpresentation.sfromVersionincludeofticFamilialHighRiskAssessmentHereditaryMyeloidMalignancyPredispositionSyndromespWhomtoTest??Bullet1new:Aberrationsofchromosome7andage<50?Bullet7revised:AllogenicsiblingrelateddonorpSubsequentSteps?Arrow3revised:Ifchromosomal...DNAorwholeexomeorgenomepFootnoteerevised:Geneticcounseling...FeursteinS,etal.Leukemia2021;35:2439-2444.MDS-E(1of6)?GeneMutationsAssociatedwithHereditaryMyeloidMalignanciespXerodermapigmentosumCnew:GeneXPCdelTG:HematologicFindings/MyeloidMalignancy:IncreasedmyeloidmalignanciesandT-cellacutelymphoblasticleukemiainpeopleaged7–29years;OtherPhenotypesandClinicalFeatures:SensitivitytoUVlight,experiencingseveresunburnswithinminutesofexposure,dryskin(xeroderma),freckling(pigmentosum),hearingloss,poorcoordination,lossofintellectualfunction,seizures,anddevelopmentofsquamouscellcarcinomasandmelanomasoftenasearlyas10yearsoldinsun-exposedareas.pERCC6L2new:Gene:ERCC6L2;HematologicFindings/MyeloidMalignancy:Marrowfailure,MDS,AML;OtherPhenotypesandClinicalFeatures:Skeletal/cardiacabnormalities,neurologicaldefectsalsoassociatedwithsomaticTP53mutationsanderythroleukemia.Pre-existingcytopenias,microcephaly,developmentaldelay,andothercongenitalabnormalities.pFootnotearevised:evolving.NotallofthelistedindividualgenesundertheGenecolumnhavebeenreportedinmyeloidmalignancies.MDS-E(2of6)?GeneMutationsAssociatedwithHereditaryMyeloidMalignanciespLIG-4syndromenew:Gene:LIG-4;HematologicFindings/MyeloidMalignancy:Marrowfailure,lymphoidmalignancy;OtherPhenotypesandClinicalFeatures:Shortstature,microcephaly,combinedimmunodeficiency.MDS-E(5of6)pGeneMutationsAssociatedwithHereditaryMyeloidMalignancies?Referencesupdated(AlsoMDS-E6of6)MDS-F?PagemovedtoMDS-B(3of3).Serumerythropoietinpriortoredbloodcell[RBC]transfusion)RBCfolateserumBcSerumferritinirontotaliron-bindingcapacity(TIBC)DocumentationoftransfusionhistoryThyroidstimulatinghormoneTSH)LactatedehydrogenaseLDHGeneticSerumerythropoietinpriortoredbloodcell[RBC]transfusion)RBCfolateserumBcSerumferritinirontotaliron-bindingcapacity(TIBC)DocumentationoftransfusionhistoryThyroidstimulatinghormoneTSH)LactatedehydrogenaseLDHGenetictestingforsomaticmutations(ie,acquiredmutations)ingenesociatedwithMDSishighlyrecommendeddRecommendadditionalmolecularandgenetictestingforhereditaryogicmalignancypredispositioninasubsetofpatientsticularlyinpatientseyoungerthanyearsofageHIVtestingifclinicallyindicatedConsiderevaluationofcopperdeficiencyinpatientswithGIeremalnutritiongastricbypasssurgeryorpatientsupplementationConsiderdistinctionfromcongenitalsideroblasticanemia(CSA)fdexINITIALEVALUATIONCytopenia(s),aaHP?Completebloodcount(CBC),platelets,differential,reticulocytecount?Examinationofperipheralbloodsmearstandardkaryotyping.bConsidertestingbonemarrowsampleforfibrosis?Bonemarrowstandardkaryotyping.bConsidertestingbonemarrowsampleforfibrosisDiagnosisofMDSestablishedbasedonmorphologic,criteriagcriteriaghificationDSaforMDSnotmettcytopeniassentSeeSpectrumofIndolentMyeloid(MDS-B,3of3)footnotesonMDSANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2022,01/13/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MDS-1PrintedbyMinTangon3/14/20227:18:48AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexFOOTNOTESFORINITIALEVALUATIONOFMDSaMDSisalsosuspectedinthepresenceofperipheralblooddysplasia,blasts,orMDS-associatedcytogeneticabnormalities.Cytopeniasaredefinedasvalueslowerthanstandardlabhematologiclevels,beingcognizantofage,sex,ethnic,andaltitudenorms.GreenbergPL,etal.Blood2016;128:2096-2097.Fordiagnosticfeaturesofprimaryandtherapy-relatedMDSthatrequirecytopenia(s)andhematopoieticcelldysplasia,SeeMDS-A(1of4).bIfstandardcytogenetics(with≥20metaphases)cannotbeobtained,achromosomemicroarray[(CMA),alsoknownaschromosomegenomicarraytesting(CGAT)]orMDS-relatedfluorescenceinsituhybridization(FISH)panelshouldbeperformed.Ifkaryotypeisnormal,thenconsiderCMA.NotethatCMAwilldetectnotonlysomaticbutalsoconstitutional(germline)changes.cRBCfolateisamorerepresentativemeasureoffolatestoresandisthepreferredtesttoserumfolate.SerummethylmalonicacidtestingisanaccuratewaytoassessB12status.dBonemarroworperipheralbloodcellsshouldbeassayedforMDS-associatedgenemutationsusinggenepanelsthatincludegeneslistedonMDS-C.Thesegenemutationscanestablishthepresenceofclonalhematopoiesis,whichcanhelpexcludebenigncausesofcytopeniasincaseswithnon-diagnosticmorphology,butdonotestablishadiagnosisofMDSintheabsenceofclinicaldiagnosticcriteria(SeeGenesFrequentlySomaticallyMutatedinMDS[MDS-C]andDiscussion).Asclonalhematopoiesisisafrequentconsequenceofaging,thefindingofmutationsinMDS-associatedgenesshouldbeinterpretedwithcautionanddoesnotinisolationestablishadiagnosisofMDS.ThemajorityofpatientswithWHO-definedMDShaveasomaticmutationdetectedinoneofthecommonlymutatedMDS-associatedgenes.eAninheritedhematologicmalignancypredispositionsyndromemayaccountforcytopeniaswithorwithoutMDSinsomepatients,whetherpresentingtopediatricoradultcarecenters(eg,GATA2deficiencysyndrome,Shwachman-Di