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NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)ChronicLymphocyticLeukemia/SmallLymphocyticLymphomarsionJuneNCCNGuidelinesforPatients?availableat/patientsVersion3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:39:08AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussion*WilliamG.Wierda,MD,PhD/Chair??TheUniversityofTexas*JenniferBrown,MD,PhD/Vice-Chair?Dana-Farber/BrighamandWomen'senterJeremyS.Abramson,MD,MMSc??MassachusettsGeneralHospitalCancerCenterFarrukhAwan,MD??TUTSouthwesternSimmonsComprehensiveCancerCenterSyedF.Bilgrami,MD?YaleCancerCenter/SmilowCancerHospitalGregBociek,MD,MSc?ξFred&PamelaBuffettCancerCenterDanielleBrander,MD?DukeCancerInstituteAsherA.Chanan-Khan,MD??MayoClinicCancerCenterSteveE.Coutre,MD?StanfordCancerInstituteRandallS.Davis,MD?O'NealComprehensiveCancerCenteratUABHerbertEradat,MD,MS??UCLAJonssonComprehensiveCancerCenteresPanelDisclosuresChristopherD.Fletcher,MD?UniversityofWisconsineCancerCenterSamehGaballa,MD?MoffittCancerCenterArminGhobadi,MD?TξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineMuhammadSaadHamid,MD?St.JudeChildren'sResearchHospital/TheUniversityofTennesseeHealthScienceCenteriscoHernandezIlizaliturriMDComprehensiveCancerCenterBrianHill,MD,PhD?CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstitutePaulKaesberg,MD?TUCDavisComprehensiveCancerCenterManaliKamdar,MD?UniversityofColoradoCancerCenterLawrenceD.Kaplan,MD?UCSFHelenDillerFamilyComprehensiveCancerCenterNadiaKhan,MD?FoxChaseCancerCenterThomasJ.Kipps,MD,PhD?UCSanDiegoMooresCancerCenterShuoMa,MD,PhD?RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityAnthonyMato,MD?MemorialSloanKetteringCancerCenterClaudioMosse,MD,PhD≠Vanderbilt-IngramCancerCenterStephenSchuster,MD??AbramsonCancerCenterheUniversityofPennsylvaniaTanyaSiddiqi,MD?CityofHopeNationalMedicalCenterDeborahM.Stephens,DO?HuntsmanCancerInstituteattheUniversityofUtahChaitraUjjani,MD?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceNinaWagner-Johnston,MD?TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsJenniferA.Woyach,MD?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandeResearchInstituteJ.ChristineYe,MD,MSc?UniversityofMichiganRogelCancerCenterξBonemarrowtransplantation?Hematology/HematologyoncologyTInternalmedicine?Medicaloncology≠Pathology/Hematopathology*DiscussionWritingCommitteeMemberVersion3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:39:08AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionlievesthatthebestmanagementforanylievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.aryoftheGuidelinesUpdatesCLL/SLLDiagnosis(CSLL-1)CLL/SLLWorkup(CSLL-2)SLL/Localized(LuganoStageI)(CSLL-3)CLL(RaiStages0–IV)orSLL(LuganoStageII–IV)(CSLL-3)CLL/SLLWithoutDeletionof17p/TP53Mutation(CSLL-4)CLL/SLLWithDeletionof17p/TP53Mutation(CSLL-5)ionforCLLSLLCSLLACLL/SLLStagingSystems(CSLL-B)SupportiveCareforPatientswithCLL/SLL(CSLL-C)SuggestedTreatmentRegimens(CSLL-D)ResponseDefinitionAfterTreatmentforCLL/SLL(CSLL-E)SpecialConsiderationsfortheUseofSmall-MoleculeInhibitors(CSLL-F)Venetoclax:RecommendedTLSProphylaxisandMonitoringBasedonTumorBurden(CSLL-G)rsandProgressionHTferentialDiagnosisofMatureBCellasmsSeeNCCNGuidelinesforBCellLymphomasTheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicalcircumstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetwork?(NCCN?)makesnorepresentationsorwarrantiesofanykindregardingtheircontent,useorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinghtsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.nibwasaddedasacategoryApreferredrecommendationrbiditiesandPatientsageynibwasaddedasacategoryApreferredrecommendationrbiditiesandPatientsageywithoutsignificantcomorbiditiesChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionUpdatesinVersion3.2022oftheNCCNGuidelinesforCLL/SLLfromVersion2.2022include:MS-1?Thediscussionsectionwasupdatedtoreflectchangesinthealgorihtm.sionoftheNCCNGuidelinesforCLLSLLfromVersionincludeGlobal?Suggestedtreatmentregimenreferenceswereupdated.CLLSLLwithoutdelpTP53CLLSLLwithoutdelpTP53mutation,First-linetherapyCSLLD2of6CLLSLLwithoutdelp/TP53mutation,Second-lineandSubsequentTherapypPatientsage≥65yCSLLD2of6CLLSLLwithoutdelp/TP53mutation,Second-lineandSubsequentTherapy?ZanubrutinibwasmovedfromanOtherrecommendedregimentoaPreferredregimenandthequalifier,"forpatientswithintoleranceorcontraindicationtootherBTKi"wasremoved.CSLL-D3of6?CLL/SLLwithdel(17p)/TP53mutation,First-lineandSecond-lineandSubsequentTherapy?ZanubrutinibwasmovedfromanOtherrecommendedregimentoaPreferredregimenandthequalifier,"forpatientswithintoleranceorcontraindicationtootherBTKi"wasremoved.CSLL-F1of3?SpecialConsiderationsfortheUseofSmall-MoleculeInhibitors?Zanubrutinib,Mostcommonadverseevents(AEs)(allgrades)andAdverseeventsofspecialinterest(AESI)updatedbasedonTamC,etal.Zanubrutinibmonotherapyforpatientswithtreatmentnaivechroniclymphocyticleukemiaand17pdeletion.Haematologica2020;106:2354-2363.UPDATESVersion3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:39:08AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionsionoftheNCCNGuidelinesforCLLSLLfromVersionincludeSuggestedtreatmentregimenandotherreferenceswereupdatedthroughouttheguidelines.SmallLymphocyticLymphoma?Diagnosis,Essentialp1stbulletrevised:Hematopathologyreviewofperipheralbloodsmearandallslides...WorkupEssentialstbulletrevised"Historyandphysicalexamincludingmeasurementofsizeofliverandspleenandpalpablelymphnodes."?Evaluateforindicationsfortreatment,Significantdisease-relatedsymptoms,thefollowingwererevised:pDrenchingnightsweatspUnintentionalweightloss(≥10%inprevious6months)?CLL/SLLwithoutdel(17p)/TP53mutationpFootnotesrevised"ConsiderBTKmutationanalysisifthepatientpreviouslyhadibrutinibintoleranceandacalabrutiniborzanubrutinibuseisplanned,aspatientswithBTKmutationareunlikelytorespondtoacalabrutiniborzanubrutinib"to"TestingforBTKandPLCG2mutationsmaybeusefulinpatientswithdiseaseprogressionornoresponsewhileonBTKinhibitortherapy.BTKandPLCG2mutationstatusaloneisnotanindicationtochangetreatment."(AlsoforCSLL-5)?CLL/SLLwithdel(17p)/TP53mutationpFirst-linetherapy,1stbullet,sub-bulletwasrevised:Chemoimmunotherapyisnotrecommendedsincedel(17p)/TP53mutationisassociatedwithlowresponserates.(AlsoaddedtoCSLL-D3of6)?Footnoteremoved:Patientswithlowpercentageofdel17p-positivecellsshouldberetestedduetochanceoffalse-positiveresults.?Footnoteremoved:Forpatientswithcomplexkaryotype(≥3abnormalities)achievingremissionwithorafterBTKinhibitortherapy,considerdiscussionofallogeneicHCT;however,availabledatadonotsupportthisashighlyeffective(JaglowskiSM,etal.BrJHaematol2012;159:82-87).?PrognosticinformationforCLL/SLLpCpG-stimulatedmetaphasekaryotyperevised:(≥3unrelatedclonalchromosomeabnormalitiesinmorethanonecellonkaryotype).CSLL-C3of5?Rarecomplicationsofmonoclonalantibodytherapy,bulletrevisedbyadding:Analternativeanti-CD20monoclonalantibodycouldbeusedforpatientswithintolerance(includingthoseexperiencingseverehypersensitivityreactionsrequiringdiscontinuationofchosenanti-CD20monoclonalantibody).CSLL-C4of5?Recurrentsinopulmonaryinfections,2ndbullet,1stsub-bulletrevisedfrom"Beginmonthlysubcutaneousimmunoglobulin(SCIG)orIVIG0.3–0.5g/kg"to"Beginmonthlyintravenousimmunoglobulin(IVIG)0.3–0.5g/kgormaysubstituteasubcutaneousimmunoglobulin(SCIG)productgivenweeklyatappropriatelyadjustedequivalentdoses."CSLL-C5of5?Vaccination,5thbulletrecommendationsforCOVID-19vaccinationadded.PrintedbyMinTangon6/4/20227:39:08AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionsionoftheNCCNGuidelinesforCLLSLLfromVersionincludeCSLL-D1of6?CLL/SLLwithoutdel(17p)/TP53mutation,First-linetherapypQualifierrevisedfrom"Frailpatientwithsignificantcomorbidity(notabletotoleratepurineanalogs)ORPatientsaged≥65yandyoungerpatientswithsignificantcomorbidities(creatinineclearance[CrCl]<70mL/min)"to"Patientsage≥65yORPatientsage<65yearswithsignificantcomorbidities(creatinineclearance[CrCl]<70mL/min)."AlsoforSecond-lineandSubsequentTherapy.pPatientsage≥65yORPatientsage<65ywithsignificantcomorbidities?Otherrecommendedregimens–Obinutuzumabwasaddedtohigh-dosemethylprednisolone(HDMP)asanalternativetorituximabwithacategory2Brecommendation.–Obinutuzumabchangedfromacategory2Btoacategory2ArecommendationpPatientsage<65ywithoutsignificantcomorbidities?Otherrecommendedregimens–HDMP+rituximabchangedfromacagtegory2Btocategory3–ObinutuzumabwasaddedtoHDMPasanalternativetorituximabwithacategory3recommendation–FR(fludarabine+rituximab)changedfroma2Btoacategory3recommendation–PCR(pentostatin,cyclophosphamide,rituximab)wasremoved?Removed:PostFirst-LineChemoimmunotherapyMaintenanceTherapy,Considerlenalidomideforhigh-riskpatients(bloodMRD≥10-2or≥10-4and<10withunmutatedIGHV)afterfirst-linetherapyCSLL-D2of6?CLL/SLLwithoutdel(17p)/TP53mutation,Second-lineandSubsequentTherapypPatientsage≥65yORPatientsage<65ywithsignificantcomorbidities?DuvelisibmovedfromPreferredtoOtherrecommendedregimens?Idelalisib+rituximabmovedfromPreferredtoOtherrecommendedregimens?Otherrecommendedregimens–HDMP+rituximabchangedfromacagtegory2Atocategory2B–ObinutuzumabwasaddedtoHDMPasanalternativetorituximabwithacategory2Brecommendation–Dose-denserituximabchangedfroma2Btoacategory3recommendation–Alemtuzumab±rituximabwasremoved–Reduced-doseFCRwasremoved–Reduced-dosePCRwasremoved–Bendamustine,rituximab+ibrutinibwasremoved–Bendamustine,rituximab+idelalisibwasremovedpPatientsage<65ywithsignificantcomorbidities?DuvelisibmovedfromPreferredtoOtherrecommendedregimens?Idelalisib+rituximabmovedfromPreferredtoOtherrecommendedregimens?Otherrecommendedregimens–HDMP+rituximabchangedfromacagtegory2Atocategory2B–ObinutuzumabwasaddedtoHDMPasalterativetorituximabwithacategory2Brecommendation–Alemtuzumab±rituximabchangedfroma2Atoacategory3recommendation–Bendamustine,rituximab+ibrutinibchangedfroma2Btoacategory3recommendation–FC+ofatumumabchangedfroma2Atoacategory3recommendation–PCRwasremoved–Bendamustine,rituximab+idelalisibwasremoved?Removed:PostSecond-LineChemoimmunotherapyMaintenanceTherapy(forcompleteorpartialresponseaftersecond-linetherapy),LenalidomideandOfatumumab(category2B).CSLL-D3of6?CLL/SLLwithdel(17p)/TP53mutation,Second-lineandSubsequentTherapypDuvelisibmovedfromPreferredtoOtherrecommendedregimenspIdelalisib+rituximabmovedfromPreferredtoOtherrecommendedregimensCSLL-D4of6?Footnotehrevised:Anti-CD20monoclonalantibodiesinclude:rituximab,ofatumumab,orobinutuzumab.WhileofatumumabisnolongercommerciallyavailableforCLL,itmaybeobtainedforclinicaluse.?Footnoteqadded:WhileofatumumabisnolongercommerciallyavailableforCLL,itmaybeobtainedforclinicaluse.ThesectionforSpecialConsiderationsfortheUseofSmall-MoleculeInhibitorswasextensivelyrevised.Version3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESCpGstimulatedmetaphasekaryotypeforcomplexkaryotypeeralbloodmarkersbckappa/lambda,CD19,CpGstimulatedmetaphasekaryotypeforcomplexkaryotypeeralbloodmarkersbckappa/lambda,CD19,CD20,CD5,CD23,CD10;ifflowisusedtoestablishdiagnosis,usuallyCD200-.alywithmonoclonalBlymphocytesxLinperipheralbloodybyIHCbCDCDCDCDCDcyclinD1.LEF1expressionmaydistinguishCLLfromMCL,whichisusuallyLEF1-.?AbsolutemonoclonalBlymphocytecountcINFORMATIVEFORPROGNOSTICAND/ORTHERAPYDETERMINATION:d?FISHtodetect:+12;del(11q);del(13q);del(17p)FlowcytometryofbloodisadequateforthediagnosisofCLL/SLL(biopsyisgenerallynoturfaceChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionDIAGNOSISaESSENTIAL:tativeofthetumorifthediagnosiswasmadeonalymphnodeorbonetativeofthetumorifthediagnosiswasmadeonalymphnodeorbonemarrowbiopsyalsoincludecytospinforalsoincludecytospinforcyclinDorfluorescenceinsituhybridizationFISHfort;14);tqvCD0positivitymaydistinguishtqvCD0positivitymaydistinguishCLLfrommantlecelllymphoma(MCL),whichisMonoclonalB-celllymphocytosis(MBL)?AbsolutemonoclonalB-lymphocytecount<5x109/L?Alllymphnodes<1.5cm?Noanemia?Nothrombocytopenia?Noorganomegaly?NoconstitutionalsymptomsMolecularanalysistodetectIGHVmutationstatuseaCasesdiagnosedasB-cellprolymphocyticleukemia(B-PLL)areexcludedfromthisguideline.bTypicalimmunophenotype:CD5+,CD23+,CD43+/-,CD10-,CD19+,CD20dim,sIgdim+,andMolecularanalysistodetectIGHVmutationstatuseaCasesdiagnosedasB-cellprolymphocyticleukemia(B-PLL)areexcludedfromthisguideline.bTypicalimmunophenotype:CD5+,CD23+,CD43+/-,CD10-,CD19+,CD20dim,sIgdim+,andcyclinD1-.Note:SomecasesmaybesIgbright+orCD23-ordim,andsomeMCLmaybeCD23+;cyclinD1immunohistochemistryorFISHfort(11;14)shouldbeconsideredinallcases,especiallyforthosewithanatypicalimmunophenotype(ie,CD23dimornegative,CD20bright,sIgbright).ofSLLshouldonlybemadewheneffacementoflymphnodearchitectureisseen.dSeePrognosticInformationforCLL/SLL(CSLL-A).eIGHVmutationstatusispreferredoverflowcytometry.Ifnotavailable,determinationofCD38,CD49d,andZAP-70expressionbyflowcytometry,methylation,orimmunohistochemistrymaybeobtainedassurrogatemarkersforIGHVmutationstatus.Evaluationofthesemarkerscanbechallengingandisnotrecommendedoutsidethesettingofaclinicaltrial.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.CSLL-1Version3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.etamicroglobulinLactatedehydrogenaseLDHicacidUnilateralbonemarrowaspiratebiopsyg?HepatitisBhandCtestingiftreatmentcontemplatedMultigatedacquisitionMUGAscan/echocardiogramifetamicroglobulinLactatedehydrogenaseLDHicacidUnilateralbonemarrowaspiratebiopsyg?HepatitisBhandCtestingiftreatmentcontemplatedMultigatedacquisitionMUGAscan/echocardiogramifanthracycline-basedregimenisPregnancytestinginwomenofchildbearingageifsystemictherapyorRTplannedDiscussionoffertilityissuesandspermbankingPETCTscantodirectnodalbiopsyifhistologictransformationissuspectedSeeHTChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionWORKUP?Historyandphysicalexamincludingmeasurementofsizeofliverandspleenandpalpablelymphnodes?Performancestatus?Bsymptoms?CBCwithdifferential?Comprehensivemetabolicpanel?QuantitativeimmunoglobulinsabdominalpelvicCTwithcontrastofdiagnosticqualityifabdominalpelvicCTwithcontrastofdiagnosticqualityifclinicallyindicatedflizedLuganoStageICLL(RaiStages0–IV)orSLL(LuganoStageII–IV)(SeeCSLL-3)fOutsideclinicaltrials,CTscansarenotnecessaryfordiagnosis,surveillance,routinemonitoringoftreatmentresponse,orprogression.CTscansmaybewarrantedfortheevaluationofsymptomsofbulkydiseaseorfortheassessmentofriskforTLSpriortoinitiatingvenetoclax.gMaybeinformativeforthediagnosisofimmune-mediatedordisease-relatedcytopenias.hHepatitisBtestingisindicatedbecauseoftheriskofreactivationduringtreatment(eg,immunotherapy,chemoimmunotherapy,chemotherapy,targetedtherapy).SeeTreatmentandViralReactivation(CSLL-C1of4).TestsincludehepatitisBsurfaceantigen(HBsAg)andcoreantibodyforapatientwithnoriskfactors.ForpatientswithriskfactorsorprevioushistoryofhepatitisB,adde-antigen.Ifpositive,checkviralloadandconsultwithgastroenterologist.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.CSLL-2Version3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:39:08AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionNCCNGuidelinesVersion3.2022NCCNnChronicLymphocyticLeukemiaSmallLymphocyticLymphomaDiscussionPRESENTATIONiSLL/Localized(LuganojStageI)CLL(RaiStagesjorSLL(LuganojgesIIIVnalRT(24–30nalRT(ifindicated)indicationsfortreatment:ligibleforclinicaltrialignificantdiseaserelatedtomsStagesinpreviousmonthsandreatenedendorganfunctionreatenedendorganfunctionressivebulkydiseasencmbelowcostalginlymphnodescmpresentgressivegressiveanemia?ProgressivethrombocytopeniamoidrefractoryautoimmunesgressivecytopenianHistologicHistologicprogressionofCLL/SLL?Priortoinitiationoftreatment,evaluatepFISHfordel(17p)pTP53mutationstatuspCpG-stimulatedkaryotype?IGHVmutationstatus(ifnotpreviouslydonenotherapyonotherapyogingasappropriateCLL/SLLWithdel(17p)/TP53Mutation(SeeCSLL-5)iSeeSupportiveCareforPatientswithCLL/SLL(CSLL-C).jSeeRaiandBinetClassificationSystems(CSLL-B1of2)andLuganoModificationofAnnArborStagingSystem(CSLL-B2of2).mPlateletcounts>100,000cells/mmaretypicallynotassociatedwithclinicalrisk.kThedoseisdeliveredin1.5–2.0Gy/fraction.SeeNCCNGuidelinesforB-CellnSelectpatientswithmild,stablecytopenia(ANC<1000/μL,Hgb<11g/dL,orLymphomas,PrinciplesofRadiationTherapyforadditionaldetails.platelet<100,000/μL)maycontinuetobefollowedwithobservation.lAbsolutelymphocytecountaloneisnotanindicationfortreatmentsinceoIGHVmutationstatusdoesnotchangeovertimeandanalysisdoesnotneedtoleukostasisisrarelyseeninCLL.berepeatedifpreviouslydonepriortoinitiationoftreatment.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.CSLL-3Version3.2022,06/03/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.iesqswithdelp?CLL/SLLwithoutdel(17p)/TP53mutationpSeeSuggested

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