骨髓增生性肿瘤2022.v3-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)MyeloproliferativeNeoplasmsNCCNGuidelinesforPatients®availableat/patientsVersion3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/15/20229:20:22AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.lasmsdex*AaronT.Gerds,MD,MS/Chair‡†ÞCaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitute*JasonGotlib,MD,MS/Vice-Chair‡StanfordCancerInstituteHarisAli,MD‡ξCityofHopeNationalMedicalCenter*PrithvirajBose,MD‡TheUniversityofTexasAndrewDunbar,MD†MemorialSloanKetteringCancerCenterAmroElshoury,MD‡RoswellParkComprehensiveCancerCenterTracyI.George,MD≠HuntsmanCancerInstituteattheUniversityofUtahKrishnaGundabolu,MBBS‡Fred&PamelaBuffettCancerCenter*ElizabethHexner,MD‡ξAbramsonCancerCenterheUniversityofPennsylvaniaGabrielaS.Hobbs,MD‡MassachusettsGeneralHospitalCancerCenteresPanelDisclosures*TaniaJain,MBBS†TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkins*CatrionaJamieson,MD,PhD‡UCSanDiegoMooresCancerCenterPaulR.Kaesberg,MD‡UCDavisComprehensiveCancerCenterAndrewT.Kuykendall,MD‡ÞMoffittCancerCenterYazanMadanat,MD‡UTSouthwesternSimmonsComprehensiveCancerCenterBrandonMcMahon,MD‡UniversityofColoradoCancerCenterSanjayR.Mohan,MD‡Vanderbilt-IngramCancerCenterKalyanV.Nadiminti,MD‡UniversityofWisconsinCarboneCancerCenterStephenOh,MD,PhD‡SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineAnimeshPardanani,MBBS,PhD‡MayoClinicCancerCenterNikolaiPodoltsev,MD,PhD‡YaleCancerCenter/SmilowCancerHospitalLindsayRein,MD‡DukeCancerInstituteRachelSalit,MD‡FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceBradyL.Stein,MD,MHS‡ÞRobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityMosheTalpaz,MD†UniversityofMichiganRogelCancerCenterPankitVachhani,MD‡O'NealComprehensiveCancerCenteratUABMarthaWadleigh,MD‡†Dana-Farber/BrighamandWomen’senterSarahWall,MD,MPH‡TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteDawnC.Ward,MD≠UCLAJonssonComprehensiveCancerCentererPhD‡Hematology/HematologiconcologyÞInternalmedicine†Medicaloncology≠PathologyξTransplantation*DiscussionWritingCommitteeMemberVersion3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.•2017WHODiagnosticCriteriaforPrimaryMyelofibrosis(MPN-A)•IWG-MRTDiagnosticCriteriaforPostPV/PostETMF(MPN-B)•2017WHODiagnosticCriteriafor•2017WHODiagnosticCriteriaforPrimaryMyelofibrosis(MPN-A)•IWG-MRTDiagnosticCriteriaforPostPV/PostETMF(MPN-B)•2017WHODiagnosticCriteriaforPVandET(MPN-C)•PrognosticSignificanceofMutationsinMPN(MPN-D)•AssessmentofSymptomBurden(MPN-E1of2)•MyeloproliferativeNeoplasmsSymptomAssessmentForm:TotalSymptomScore(MPN-SAFTSS;MPN-10)(MPN-E2of2)•SupportiveCareforPatientswithMPN(MPN-F)•SpecialConsiderationsfortheUseofJAKInhibitors(MPN-G)•SpecialConsiderationsintheTreatmentofPVandET(MPN-H)•DefinitionofResistance/IntolerancetoHydroxyurea(MPN-I)lasmsdexiferativeNeoplasmsPanelMembersryoftheGuidelinesUpdatesMyeloproliferativeNeoplasms:•Workup(MPN-1)•DiagnosisandRiskStratification(MPN-2)Myelofibrosis:•TreatmentforLower-RiskMyelofibrosis(MF-1)•TreatmentforHigher-RiskMyelofibrosis(MF-2)•ManagementofMF-AssociatedAnemia(MF-3)•DiseaseProgressiontoAdvanced-Phase/AML(MF-4)•RiskStratificationforPatientswithMyelofibrosis(MF-A)•2013IWG-MRTANDELNResponseCriteriaforMF(MF-B)PolycythemiaVera:•TreatmentforLow-RiskPolycythemiaVera(PV-1)•TreatmentforHigh-RiskPolycythemiaVera(PV-2)•2013IWG-MRTandELNResponseCriteriaforPV(PV-A)•RiskStratificationforPatientswithPolycythemiaVera(PV-B)EssentialThrombocythemia:•TreatmentforVery-Low-RiskorLow-RiskET(ET-1)•TreatmentforIntermediate-RiskEssentialThrombocythemia(ET-2)•TreatmentforHigh-RiskEssentialThrombocythemia(ET-3)•2013IWG-MRTANDELNResponseCriteriaforET(ET-A)•RiskStratificationforPatientswithEssentialThrombocythemia(ET-B)Myelodysplastic/MyeloproliferativeNeoplasms(MDS/MPN):SeetheNCCNGuidelinesforMyelodysplasticSyndromesbelievesthatthebestnagementforanypatientwithcancerisinatrialoninclinicaltrialsisespeciallyencouragednsNCCNCategoriesofEvidenceandConsensus:Allrecommendationsarecategory2Aunlessotherwiseindicated.SeeNCCNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2022.Version3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.andmonitorfordiseaseprogressionforpatientswithsymptomaticlower-continuedneartothestartofconditioningtherapyfortheimprovementofriskMFwithnoresponseorlossofresponse.splenomegalyandotherdisease-relatedsymptomsandmonitorfordiseaseprogressionforpatientswithsymptomaticlower-continuedneartothestartofconditioningtherapyfortheimprovementofriskMFwithnoresponseorlossofresponse.splenomegalyandotherdisease-relatedsymptoms...(AlsoforMF-4).•Footnote"f"modified:ClinicalbenefitmaynotreachthethresholdoftheMF-3IWGResponseCriteriaandcontinuationofruxolitinibJAKinhibitorsis•Footnote"n"modified:RuxolitiniborfedratinibJAKinhibitorsmaybepriorJAKinhibitorforpatientswithhigher-riskMFwhoarenottransplantlimiteddataregardingtheuseoffedratiniborpacritinibwithHMAs.correspondingtoAlternateoptionnotusedbeforeandmonitorfordisease•Pacritinibhasbeenaddedto"SpecialConsiderationsfortheuseofJAKInhibitors".Footnotefmodified:Clinicalbenefitmaynotreachthethresholdoftherecommendedbasedonthediscretionofthecliniciancontinuedfortheimprovementofsplenomegalyandotherdisease-relatedfootnotecorrespondingtoAlternateoptionnotusedforinitialtreatment•Modifiedfootnote"k":RuxolitiniborfedratinibJAKinhibitorsmaybe•Considerpacritinibforpatientswithplateletcounts≥50x109/Lwithoneofsplenomegalyorotherdisease-relatedsymptoms.ThereareverycandidatesandwithnoresponseorlossofresponseisanewfootnoteMPN-G(5of7)andMPN-G(6of7)progression.lasmsdexsionoftheNCCNGuidelinesforMyeloproliferativeNeoplasmsfromVersionincludeMPN-F1of3•Sub-bullet1underVaccinations:Considerrecombinant(killed)zostervaccineforpatientson,ruxolitinibandfedratiniborpriorto,treatmentwithaJAKinhibitor.MS-1•Thediscussionsectionhasbeenupdatedtoreflectthechangesinthealgorithm.UpdatesinVersion2.2022oftheNCCNGuidelinesforMyeloproliferativeNeoplasmsfromVersion1.2022include:•Considerpacritinibforpatientswithplateletcounts<50x109/L,isa•Considerpacritinibforpatientswithplateletcounts<50x109/L,isanewinhibitorsisrecommendedbasedonthediscretionoftheclinician...•Pacritinibaddedasa•PacritinibaddedasatreatmentoptionforpatientswhoarenotMF-4recommendationusedincombinationwithHMA(azacitidineordecitabine)forthepalliationtransplantcandidateswithplatelets<50x109/L.Thisisacategory2ArecommendationusedincombinationwithHMA(azacitidineordecitabine)forthepalliationsionoftheNCCNsionoftheNCCNGuidelinesforMyeloproliferativeNeoplasmsfromVersioninclude•Bullet8,modified:Moleculartesting(bloodorbonemarrow)•Columnmutationalprognostication,isanewsub-bullet.•"m"modified:Erythropoiesis-mutationalprognostication,isanewsub-bullet.odelsincorporatingothermutationshavebeen•"n"Prostatecancerscreeningformenproposedtoidentifypatientsproposedtoidentifypatientswithmyelofibrosis(MF)aswellasPVandETtobettertobetterestimateoverallsurvivalmyelofibrosisfreesurvivalPVandETwhomaybeatriskofandratesofleukemictransformation•"u",modifiedwhomaybeatriskofandratesofleukemictransformationPlatelets≥50XPlatelets≥50X109/L,NotatransplantcandidateMF-A1of5•PrimaryMFMyelofibrosis(PMF)ommendationfromacategoryBommendationfromacategoryBUPDATESVersion3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/15/20229:20:22AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.lasmsdexionoftheNCCNGuidelinesforMyeloproliferative•Ropeginterferonalfa-2b-njft:pisacategory2Brecommendationforlow-riskpolycythemiaveraunderotherrecommendedregimen.•Column5,Bullet2,modified:Frequentphlebotomyand/orpersistentneedforphlebotomy,butwithpoortoleranceintolerantofphlebotomy(AlsoforPV-2).•Ropeginterferonalfa-2b-njft:pColumn2:otherrecommendedregimenforhigh-riskploycythemiaverapColumn6:ifnotpreviouslyused,underotherrecommendedregimen•Ruxolitinib(category1)recommendationforhigh-riskPVfroma(category2A)•Deleted:Busulfan(PO)(category2B)(especiallyforolderadults)Usefulincertaincircumstances(alsoforET-4).•"j":modifiedtoincludetherapythatdeferhydroxyureaorropeginterferonalfa-2b-njft.•Deleted:AlvarezLarranA,etal.AnnHematol2014;93:2037-2043.(AlsoforET-4)NewpageforMIPSS-PVriskstratificationwiththefollowingreference:TefferiA,GuglielmelliP,LashoTL,etal.Mutation-enhancedinternationalprognosticsystemsforessentialthrombocythaemiaandpolycythaemiavera.BrJHaematol.2020;189:291-302.ET-1•Addedthefollowingto"very-low-risk":(Age≤60years,noJAK2mutation,nopriorhistoryofthrombosis)p"and/orlow-riskJAK2-positivepatients"wasremoved.•Addedthefollowingto"low-risk":(Age≤60years,withJAK2mutation,nopriorhistoryofthrombosis)p"forpatientswithvasomotor/microvasculardisturbancesand/orlow-riskJAK2-positivepatients"wasremoved.ET-2•AddedthefollowingtoIntermediate-risk(Age>60years,noJAK2mutation,nopriorhistoryofthrombosis)p"forvasomotor/microvasculardisturbances"wasremoved.•AddedthefollowingtoHigh-risk(Historyofthrombosisatanyage;or,age>60yearswithJAK2mutation)•Column2,Bullet1,modifiedtoinclude"oranagrelide".ioninclude•NewpageforMIPSS-ETriskstratificationwiththefollowingreference:TefferiA,GuglielmelliP,LashoTL,etal.Mutation-enhancedinternationalprognosticsystemsforessentialthrombocythaemiaandpolycythaemiavera.BrJHaematol.2020;189:291-302.MPN-F(1of3)•Bullet8,sub-bulletsdeleted:pHydrationand/ordiuresispConsidermanagementofhyperuricemiawithallopurinolorrasburicase.pRasburicaseshouldbeconsideredasinitialtreatmentinpatientswithrapidlyincreasingblastcounts,highuricacid,andevidenceofimpairedrenalfunction.MPN-H(1of4)•Bullet1,sub-bullet2,modified:Consideraspirinforpatientswithothercardiovascularriskfactors.Therisksandbenefitsofaspirinplusanticoagulationneedtobeindividualizedonacase-by-casebasis.(referstoallsubtypes)(SeeET-1andET-2).pSub-bullet3,3rdsentence,modified:CautionisrequiredwhenusingantiplateletagentswithanticoagulantsforthetreatmentofthrombosisthromboticdisordersinpatientswithPV.pSub-bullet4,3rdsentence,modified:Thevalueofcytoreductioninreducingfuturevasculareventshasnotbeenstudiedinaprospective,randomizedcontrolledtrialsinPV.•Bullet2,sub-bullet2,2ndsentence,modified:Considertheuseofappropriatecytoreductivetherapytooptimizenormalizeplateletcountswhileminimizinghematologicandnon-hematologictoxicities,seediscussion.•ReferenceupdatedtoZwickerJI,ParanagamaD,LessenDS,etal.Hemorrhageinpatientswithpolycythemiaverareceivingaspirinwithananticoagulant:Aprospective,observationalstudy.Haematologica2021Jun24.doi:10.3324/haematol.2021.279032.Onlineaheadofprint.MPN-H(2of4)and(3of4)•Terminologiesmodifiedtobemoreinclusiveofallsexualandgenderidentities.•Thesectionon"Pregnancy"hasbeensignificantlyedited.ReferencesHematologicmalignanciesinpregnancy:Managementguidelinesfromaninternationalconsensusmeeting.JClinOncol2016;34:501-508,isnewreferringto"DefinitionofHigh-RiskPregnancyinMPN".nosticationeSuspicionof rativeasmsMPNaPrintedbyMinTangon8/15/20229:20:22AM.FornosticationeSuspicionof rativeasmsMPNalasmsdexWORKUP•H&P,includingspleensizebypalpation,evaluationofthrombotic/hemorrhagiceventsandcardiovascularriskfactors•CBCwithdifferential•Comprehensivemetabolicpanelwithuricacid,lactatedehydrogenase(LDH),andliverfunctiontests(LFTs)•FISHormultiplexRT-PCR(ifavailable)forBCR-ABL1toexcludethediagnosisofCML;ifBCR-ABL1-positive,SeeNCCNGuidelinesforChronicMyeloidLeukemia•Examinationofbloodsmearstainbcd•Bonemarrowaspiratewithironstain;bonemarrowbiopsywithstainbcdBonemarrowcytogeneticsblood,ifbonemarrowisinaspirable)(karyotypewithorwithout•Moleculartesting(bloodorBonemarrowcytogeneticsblood,ifbonemarrowisinaspirable)(karyotypewithorwithoutwithPV)ormoleculartestingusingmultigeneNGSpanelthatincludesJAK2,CALR,andMPLeandMPLmutationswithPV)ormoleculartestingusingmultigeneNGSpanelthatincludesJAK2,CALR,andMPLeIfthereisevidenceofmastIfthereisevidenceofmastcellaggregatesinthebonemarrow,SeeNCCNGuidelinesfor•AssessmentofsymptomburdenusingMPNSymptomAssessmentFormTotalSymptomScore(MPN-SAFTSS;MPN-10;MPN-E2of2)•Documentationoftransfusion/medicationhistory•Humanleukocyteantigen(HLA)testing,ifconsideringallogeneichematopoieticcell•Serumerythropoietin(EPO)level•Serumironstudies•uutisneuiredvonWillebranddisease(VWD)and/orotherpProthrombintime(PT),partialthromboplastintime(PTT),fibrinogenSeeWorkupintheNCCNGuidelinesforSystemicePrognosticmodelsincorporatingotherSeeWorkupintheNCCNGuidelinesforSystemic(MF)aswellasPVandETtobetterestimateoverallsurvival,myelofibrosis-freesurvival(PVandET),andloidLymphoidNeoplasmswithratesofleukemictransformation.Next-generationsequencing(NGS)loidLymphoidNeoplasmswithhiliaandTyrosineKinaseFusionGenesbSeeWHODiagnosticCriteriaforPrimaryselectedcircumstanceshiliaandTyrosineKinaseFusionGenesbSeeWHODiagnosticCriteriaforPrimarySeeMPN-cd)WHODiagnosticCriteriaforPVandET.Seemaybeusefulundercertaincircumstances.maybeusefulundercertaincircumstances.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MPN-1Version3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/15/20229:20:22AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.lasmsdexDIAGNOSISi,jMyelofibrosisPolycythemiavera(PV)dthrombocythemiaET)FootnotesonMPNAPROGNOSTICRISKMODELPrimarymyelofibrosis(PMF)b•MIPPS-70orMIPSS-70+Version2.0(preferred)•DIPSS-Plus(ifmoleculartestingisnotavailable)or•DIPSS(ifkaryotypingisnotavailable)Post-PVorPost-ETMFc•MYSEC-PMnalriskmodelksisrevisedlRISKSTRATIFICATIONLower-risk(MF-1)•MIPSS-70:≤3•MIPSS-70+Version2.0:≤3•DIPSS-Plus:≤1DIPSS≤2MYSECPM<14Higher-risk(MF-2)•MIPSS-70:≥4•MIPSS-70+Version2.0:≥4•DIPSS-Plus:>1DIPSS>2MYSECPM≥14Low-risk(PV-1)•Age<60yearsandnopriorhistoryofthrombosisHigh-risk(PV-2)•Age≥60yearsand/orpriorhistoryofthrombosisVery-low-risk(ET-1)•Age≤60years,noJAK2mutation,nopriorhistoryofthrombosisLow-risk(ET-1)•Age≤60years,withJAK2mutation,nopriorhistoryofthrombosisIntermediate-risk(ET-2)•Age˃60years,noJAK2mutation,nopriorhistoryofthrombosisHigh-risk(ET-3)•Historyofthrombosisatanyageorage>60yearswithJAK2mutationNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MPN-2Version3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/15/20229:20:22AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.lasmsdexbSee2017WHODiagnosticCriteriaforPrimaryMyelofibrosis.See(MPN-A).cDiagnosticcriteriaforpost-ETorpost-PVMF.See(MPN-B).dSee2017WHODiagnosticCriteriaforPVandET.See(MPN-C).iThediagnosisofMPNisbasedonthe2017WHOCriteriaandrequiresacombinationofclinical,laboratory,cytogenetic,andmoleculartests.jReferraltospecializedcenterswithexpertiseinthemanagementofMPNisstronglyrecommendedforallpatientsdiagnosedwithMF,PV,orET.kMarchioliR,etal.JClinOncol2005;23:2224-2232.lTherevisedInternationalPrognosticScoreofThrombosisforET(IPSET-thrombosis)ispreferredfortheriskstratificationofET(HaiderM,etal.AmJHematol2016;91:390-394.BarbuiT,etal.BloodCancerJ2015;5:e369).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MPN-2AVersion3.2022,08/11/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.Lower-riska(MPN-10;rialincircumstances:Ruxolitinibssymptomsse Peginterferonalfa-2aNEofevery3–6reaifLower-riska(MPN-10;rialincircumstances:Ruxolitinibssymptomsse Peginterferonalfa-2aNEofevery3–6reaifctionwouldaticallyldexTREATMENTFORLOWER-RISKMYELOFIBROSISContinueobservation(if•symptomaticContinueobservation(if•symptomaticandmonitorforandsymptomsondiseaseprogressionondiseaseprogressionc(MPN- Asymptomatic Asymptomaticrialomaticpatientsshould•(MPN-10;rialomaticpatientsshould•edasnotedbelowAssessedasnotedbelowAssesssymptomburdenusingMPN-SAFTSSResponseorLossDiseaseprogressiongContinuetreatmentiseaseprogressionciseaseprogressioncefMPNMPNEof)AlternateoptionnotusedforinitialtreatmentandefefhMPNMPNEof)Higher-riskseeMF-2;andAdvancedstageMF/AML,seeMF-4aEvaluationforallogeneicHCTisrecommendedforpatientswithlowplateletcountsorcomplexcytogenetics.Identificationof“higher-risk”mutationsmaybehelpfulinthedecision-makingregardingallogeneicHCTforpatientswithPMF.SeePrognosticSignificanceofMutationsinMPN(MPN-D).eSeeSpecialConsiderationsfortheUseofJAKInhibitors(MPN-G).beSeeSpecialConsiderationsfortheUseofJAKInhibitors(MPN-G).fClinicalbenefitmaynotreachthethresholdoftheIWGResponsefClinicalbenefitmaynotreachthethresholdoftheIWGResponseCriteriaandcontinuationofJAKinhibitorsisrecommendedbasedonthediscretionoftheclinician.See2013IWG-MRTandELNResponseCriteriaforMF(MF-B).gAdditionalmoleculartestingusingmulti-geneNGSpanelshouldbeconsideredtoevaluateforhigher-riskmutationsassociatedwithdiseaseprogressioninpatientswithprimaryPMF.SeePrognosticSignificanceofMutationsinMPN(MPN-D).asclinicallyindica