Follicular Lymphoma - NORD (National Organization for Rare ...

Follicular lymphoma is a form of cancer. It is a type of non-Hodgkin lymphoma (NHL), which is a group of related cancers that affect the lymphatic system ... ScrollToTopAboutNewsEventsContactPODCASTStoredonateMenuforPatientsandFamiliesInformation&ResourcesRareDiseaseInformationRareDiseaseVideoLibraryPatientandCaregiverResourceCenterInformationonClinicalTrialsandResearchStudiesGeneTherapyRareDiseaseCentersofExcellenceCOVID-19ResourcesHelptoAccessMedicationsPatientAssistanceProgramsOtherFinancialAssistanceConnectwithOthersFindaPatientOrganizationRareDiseaseDay®PatientStoriesTakeActionAttendEventsAdvocateSupportCloseforPatientOrganizationsJoinMembershipNetworkValueofMembershipMembershipCriteriaApplyforMembershipNonprofitResourcesMembershipBenefitsMembershipResourcesRareLaunch®WebinarSeriesDiversity,Equity&InclusionOtherWaystoPartnerGrowyourorganizationPatientRegistriesAdvocacyRareDiseaseDay®RDCA-DAP®MembershipProfilesAboutourMembersMemberListRareCancerCoalition®CloseforCliniciansandResearchersResourcesResourcesforMedicalProfessionalsRareDiseaseInformationResourcesforyourPatientsContinuingMedicalEducationResearchOpportunitiesResearchGrantProgramRequestsforProposalsResearchGrantRecipientsConnectLendYourExpertiseRareDiseaseDay®CloseNORDRareDiseaseAdvocacyNORD’sPolicyinActionIssueOverviewsNORDontheIssuesNORDStateReportCardNationalPartnershipsTakeActionLocallyJointheRareActionNetwork®ProjectRDACContactYourRepresentativesTakeActionRareInsights®RareInsights®5MythsAboutOrphanDrugsandtheOrphanDrugActCloseGetInvolvedDonateNowGiveWaystoGiveDonatetoResearchNORD®StoreEducateEducationalInitiativesRaiseAwarenessIdentifyRareDiseaseExpertsJoinParticipateinEventsBecomeaMemberRareCancerCoalition®EmploymentOpportunitiesCorporateCouncilAbouttheCorporateCouncilCurrentMembersCouncilCodeofConductJointheCouncilCloseHome/ForPatientsandFamilies/RareDiseaseInformation/FollicularLymphomaRareDiseaseDatabase0-9•A•B•C•D•E•F•G•H•I•J•K•L•M•N•O•P•Q•R•S•T•U•V•W•X•Y•ZPrintFollicularLymphomaNORDgratefullyacknowledgesJamesArmitage,MD,TheJoeShapiroProfessorofMedicine,DivisionofOncology&Hematology,DepartmentofInternalMedicine,CollegeofMedicine,UniversityofNebraskaMedicalCenter,forassistanceinthepreparationofthisreport.SubdivisionsofFollicularLymphomapediatricfollicularlymphomaprimarygastrointestinalfollicularlymphomatransformedfollicularlymphomaGeneralDiscussionFollicularlymphomaisaformofcancer.Itisatypeofnon-Hodgkinlymphoma(NHL),whichisagroupofrelatedcancersthataffectthelymphaticsystem(lymphomas).Thelymphaticsystemfunctionsaspartoftheimmunesystemandhelpstoprotectthebodyagainstinfectionanddisease.Itconsistsofanetworkoftubularchannels(lymphvessels)thatdrainathinwateryfluidknownaslymphfromdifferentareasofthebodyintothebloodstream.Lymphaccumulatesinthetinyspacesbetweentissuecellsandcontainsproteins,fats,andcertainwhitebloodcellsknownaslymphocytes.Aslymphmovesthroughthelymphaticsystem,itisfilteredbyanetworkofsmallstructuresknownaslymphnodesthathelptoremovemicroorganisms(e.g.,viruses,bacteria,etc.)andotherforeignbodies.Groupsoflymphnodesarelocatedthroughoutthebody,including,butnotlimitedto,theneck,underthearms(axillae),attheelbows,andinthechest,abdomen,andgroin.Lymphocytesarestoredwithinlymphnodesandmayalsobefoundinotherlymphatictissues.Inadditiontothelymphnodes,thelymphaticsystemincludesthespleen,whichfiltersworn-outredbloodcellsandproduceslymphocytes,andbonemarrow,whichisthespongytissueinsidethecavitiesofbonesthatmanufacturesbloodcells.Lymphatictissueorcirculatinglymphocytesmayalsobelocatedinotherregionsofthebody.Therearetwomaintypesoflymphocytes:B-lymphocytes(B-cells),whichmayproducespecificantibodiesto“neutralize”certaininvadingmicroorganisms,andT-lymphocytes(T-cells),whichmaydirectlydestroymicroorganismsorcancercells,orassistintheactivitiesofotherlymphocytes.FollicularlymphomaisaB-celllymphoma.ItischaracterizedbythetransformationofaB-cellintoamalignant(cancerous)cell.Abnormal,uncontrolledgrowthandmultiplication(proliferation)ofmalignantB-cellscanleadtoenlargementofspecificlymphnoderegions;involvementofotherlymphatictissuessuchasthespleenorbonemarrow;andspreadtootherbodilytissuesandorgans.Thetermfollicularlymphomacomesfromtheobservationthatthecancercellsaregroupinclusters(orfollicles)withinthelymphnodes.Non-Hodgkinlymphomaincludingfollicularlymphomacanbecharacterizedas“low-grade”(orindolent),meaningthecancertendstogrowslowlyandresultsinfewassociatedsymptomsor“high-grade”(aggressive),meaningthecancertypicallygrowsrapidly.Signs&SymptomsThespecificsymptomsandphysicalfindingsoffollicularlymphomacanvaryfromonepersontoanother,dependingupontheextentandregion(s)ofinvolvementandotherfactors.Follicularlymphomaisdescribedashavingarelapsingandremittingcourse;thecanceralternatesbetweenflaringuporworseningforaperiodoftimeoftenrequiringtreatment,andperiodsoftimewherethecancerisinremissionorlevelsoff.Formanypeople,follicularlymphomaisaslow-growingcancerthatdevelopsovermanyyears.Acommonfindingistheenlargementofaffectedlymphnodes(lymphadenopathy).Lymphnodesmaybecomehardandcanbefelt(palpable)underneaththeskin.Lymphnodesintheneck,thearmpit(axilla),andgroinaremostcommonlyaffected.Lymphnodesintheabdomencanalsobecomeenlarged,butcannotbefelt.Lymphnodeenlargementismostlypainless.Theenlargementofalymphnodemaycomeandgoforseveralyearsbeforeadiagnosisoffollicularlymphomaismade.Follicularlymphomacanaffectthebonemarrowandthespleen,causingabnormalenlargementofthespleen(splenomegaly).Whenfollicularlymphomaaffectsthebonemarroworthespleen,itcanleadtolowlevelsofthethreemainbloodcelltypes:redbloodcells,whitebloodcells,andplatelets.Thisiscalledcytopenia.Redbloodcellsdeliveroxygentothebody,whitebloodcellshelpinfightingoffinfectionsandplateletsallowthebodytoformclotstostopbleeding.Alowlevelsofredbloodcellsiscalledanemiaandcanbecharacterizedbytiredness,shortnessofbreath,weakness,lightheadedness,headaches,andpaleskincolor.Alowlevelsofwhitebloodcells(neutropenia)increasestheriskofcontractingbacterialandfungalinfections.Alowlevelsofplatelets(thrombocytopenia)makestheindividualmoresusceptibletoexcessivebruisingfollowingminimalinjuryandspontaneousbleedingfromthegumsandnose.Lessoften,affectedindividualsdevelopsymptomsthatarevagueandcanbenonspecific,whichmeansthatthesymptomsarecommontomanydifferentdisordersorconditions.Whendealingwithlymphoma,thesesymptomsmaycomeandgoandaresometimesreferredtoas‘Bsymptoms.’Thesesymptomscanincludeapersistent,chronicfever;unintendedweightloss,andexcessivesweating,especiallyatnight(nightsweats).Follicularlymphomaaffectingorgansotherthanthoseinthelymphaticsystemorthebonemorrowisrare.Sometimes,largetumorsmayformintheabdomen.TransformedFollicularLymphomaThereisariskinindividualswithfollicularlymphomathatthecancercangounderatransformationfromaslow-growing(indolent)formintoamoreaggressiveformcalleddiffuselargeB-celllymphoma(DLBCL).Asmanyas30-40%ofindividualsmayexperienceaggressivetransformationofindolentfollicularlymphoma.DLBCLcanprogressrapidlyandspreadtoareasandorgansoutsideofthelymphaticsystem(extranodal)andthebonemarrow.‘B’symptomsaremorecommonintransformedfollicularlymphoma.PrimaryGastrointestinalFollicularLymphomaPrimarygastrointestinalfollicularlymphomaoftendoesnotcauseanyapparentsymptoms(asymptomatic).Thisformisgenerallyconsideredtobeadistinctvariantoffollicularlymphomathathasabetterprognosis.Canceroftenarisesinthefirstsectionofthesmallintestines(duodenum),whichconnectstothestomach.Affectedindividualscandevelopabdominaldiscomfortandheartburn.Lessoften,affectedindividualscandevelopnausea,vomiting,diarrhea,abdominalpain,andintestinalbleeding,whichcancauseblack,tarrystools.PediatricFollicularLymphomaPediatricfollicularlymphomaisdifferentfromtheadultformandisconsideredadistincttypeoflymphomabymanyresearchers.Differentgeneticfactorshavebeenshowntoplayaroleinthepediatricformthanareseeninfollicularlymphoma.Pediatricfollicularlymphomaischaracterizedbythecancerremainingintheareawhereitfirstdevelops(localizedpresentation).Enlargementofthelymphnodesisthemostcommonsymptom.Overall,pediatricfollicularlymphomashowsagenerallybenignbehavior.Thelymphnodesfoundintheneck(cervicalarea)andthetonsilsaremostoftenaffected.Thegastrointestinaltract,salivaryduct,kidney,andskincanalsobeaffected.Someresearchersusethetermpediatric-typefollicularlymphomabecauseadultswiththisformoffollicularlymphomahavebeenidentified.CausesTheexact,underlyingcauseoffollicularlymphomaisnotfullyunderstood.Thereasonwhycancerdevelopsisacomplexquestionandresearchersspeculatethatmultiplefactorsareinvolvedinthedevelopmentoffollicularlymphoma.Thesefactorsincludegenetic,environmentalandimmunologicfactors,whichallmayplayaroleinthedevelopmentofthiscancer.About85%ofaffectedadultshaveageneticabnormalitythatisnotinherited,butfoundonlywithinthecancercellscalledatranslocation.Atranslocationisageneticabnormalityinwhichregionsofcertainchromosomesbreakoffandarerearranged,resultinginshiftingofgeneticmaterialandanalteredsetofchromosomes.Infollicularlymphoma,regionsofchromosome14and18breakoffandtradeplaces.Chromosomes,whicharepresentinthenucleusofhumancells,carrythegeneticinformationforeachindividual.Humanbodycellsnormallyhave46chromosomes.Pairsofhumanchromosomesarenumberedfrom1through22andthesexchromosomesaredesignatedXandY.MaleshaveoneXandoneYchromosomeandfemaleshavetwoXchromosomes.Eachchromosomehasashortarmdesignated“p”andalongarmdesignated“q”.Chromosomesarefurthersub-dividedintomanybandsthatarenumbered.Thegenetictranslocationinvolvingchromosomes14and18leadstotheoverexpressionofagenecalledBCL-2.Genesprovideinstructionsforcreatingproteinsthatplayacriticalroleinmanyfunctionsofthebody.Whenamutationofageneoccurs,theproteinproductmaybefaulty,inefficient,absent,oroverproduced.OverexpressionmeansthattheproteinproductoftheBCL-2geneisoverproduced.Theproteinproducedbythisgeneisbelievedtoplayaroleininhibitingapoptosis,thenormalprocessbywhichcellsgrowandthendie(programmedcelldeath).BecausetheBCL-2geneisoverexpressed,itpreventscellsfromgoingthroughapoptosis,causingcellsthatdonotdieoffwhentheyaresupposedto.Thiscontributestothedevelopmentofcancer.Althoughthemajorityofadultswithfollicularlymphomahavethisspecificgenetictranslocation,therearepeopleinthegeneralpopulationwhoalsohavethisspecifictranslocation,butwhoneverdevelopfollicularlymphoma.Thissuggeststhatadditionalfactors,includingothergeneticalterationsorchanges,arerequiredforthedevelopmentoffollicularlymphoma.Forexample,alterations(mutations)inagenecalledEZH2havebeenreportedinmorethan25%ofpeoplewithfollicularlymphomaandmayplayaroleinthecancer’sdevelopment.Moreresearchisnecessarytofullyunderstandthecomplexgeneticinteractionsthatcontributetothedevelopmentoffollicularlymphoma.Environmentalfactorsthathavebeensuggestedtopossiblyplayaroleinthedevelopmentoffollicularlymphomaincludeexposuretotoxicsubstanceslikebenzene,occupationalexposuretopesticides,certaininfections,andsmokingincludingpassivesmoking.Theunderlyinggeneticsdifferbetweentheadultandpediatricforms.Childrenwithfollicularlymphomadonothaveatranslocationinvolvingchromosomes14and18.Thegeneticfactorsinvolvedinpediatricfollicularlymphomaarenotfullyknown.MutationsintheMAP2K1geneandmutationsordeletionsintheTNFRSF14genehavebeencommonlyreportedinthemedicalliterature.Moreresearchisnecessarytodeterminethecomplexgeneticfactorsthatareinvolvedinpediatricfollicularlymphoma.AffectedPopulationsFollicularlymphomaaffectsbothmenandwomen,butisslightlymorecommoninwomen.Thisformofcancerisfoundallovertheworldandcanaffectpeopleofallraces.ItislesscommoninindividualsofAsianorAfricanheritagethanitisinotherethnicities.Themeanageatdiagnosisis65.IntheUnitedStatesandWesternEurope,follicularlymphomaisthesecondmostcommonsubtypeofnon-Hodgkinlymphomaaccountingforabout30%-35%ofpeoplewithnon-Hodgkinlymphomaandalmost75%ofpeoplewithindolentformsoflymphoma.Eachyear,15-20,000peopleintheU.S.arediagnosedwithfollicularlymphoma.Pediatricfollicularlymphomaisextremelyrarevariantthatmakesuponly1-2%ofallmalignantlymphomasinchildren.Non-Hodgkinlymphoma,asagroup,accountsforabout4.3%ofpeoplewithcancerintheUnitedStates.RelatedDisordersSymptomsofthefollowingdisorderscanbesimilartothoseoffollicularlymphoma.Comparisonsmaybeusefulforadifferentialdiagnosis.Varioustypesoflymphomaneedtobedifferentiatedfromfollicularlymphoma.TherearetwomajorcategoriesoflymphomacalledHodgkindisease(lymphoma)andnon-Hodgkinlymphoma(NHL).HodgkindiseaseistypicallycharacterizedbythepresenceofaspecifictypeofcancercellknownasaReed-Sternbergcellthathasmorethanonenucleus.ThiscellisamatureB-lymphocyte(B-cell)thathasbecomemalignant.NHLisbroadlycategorizedintolymphomasthatarisefromtwodifferenttypeofcells,B-lymphocytesorT-lymphocytes(T-cells).TherearemanyformsofNHL.Mantlecelllymphoma,cutaneousfolliclecentercelllymphoma,T-cellrichlargeB-celllymphoma,andnodalmarginalzonelymphomaarespecificsubtypesofNHLthatshoulddifferentiatedfromfollicularlymphoma.(Formoreinformationonsomeofthesedisorders,choosethespecifictypeoflymphomaasyoursearchtermintheRareDiseaseDatabase.)DiagnosisAdiagnosisoffollicularlymphomaisbaseduponidentificationofcharacteristicsymptoms,adetailedpatienthistory,athoroughclinicalevaluationandavarietyofspecializedtests.Suchtestingisnecessarytoconfirmthespecifictype(andsubtype)ofnon-Hodgkinlymphoma,todeterminethenatureandextentofthecancer,andtodeterminethemostappropriatetreatments.Duringacompletephysicalexamination,physiciansmayfeel(i.e.,palpate)thelymphnodesincertainregionstodetectanyswelling,includingintheneck,tonsil,andadenoidalregion;underthearms;andinthegroin.Theymayalsoexamineotherregionstohelpdeterminewhetherthereisenlargementofcertaininternalorgans,particularlythespleen,andtodetectswellingandabnormalfluidaccumulationthatmaybeassociatedwithdiseaseofthelymphaticsystem.Forthosewithsuspectedlymphomaassuggestedbythoroughpatienthistoryandclinicalexamination,variousdiagnostictestsmayberecommended.Thesemayincludebloodtests,biopsies,specializedimagingtests,bonemarrowexamination,and/orothertests.ClinicalTestingandWorkupAdiagnosisoffollicularlymphomarequiresthereviewofanadequatebiopsysamplebyanexpertmedicalpathologist.Pathologistsarephysicianswhospecializeinanalyzingcellsandtissuestohelpobtainaccuratediagnosis.Biopsiestypicallyinvolvetheremovalandmicroscopic(i.e.,histologic)examinationofsmallsamplesoftissuecellsfromalymphnode–or,insomeinstances,removalofanentire,enlargedlymphnode–thatissuspectedofbeingcancerous.Dependinguponthespecifictypeofbiopsyperformed,theproceduremaybeconductedunderlocalorwholebody(general)anesthesia.Inaddition,insomeinstances,suchaswheninvolvementappearstoberestrictedtotheabdominalorpelvicregion,laparoscopyorlaparotomymaybenecessarytoobtainbiopsysamples.Laparoscopyinvolvesexaminationoftheabdominalcavitywithanilluminatedviewingtube(laparoscope)insertedthroughincisionsintheabdominalwall.Laparotomyisasurgicalprocedureinwhichtheabdomenisopened,organsarecarefullyexaminedtodetectsignsofdisease,andsamplesoftissueareremovedformicroscopicexamination.Sometimes,doctorsmayrecommendabonemarrowbiopsytodeterminewhetherlymphomaisinthebonemarrow.Bloodtestsmayincludestudiestoevaluatethenumberandappearanceofwhitebloodcells,redbloodcells,andplatelets;liverenzymestudies;teststomeasurelevelsoftheenzymelactatedehydrogenase(LDH);and/orotherstudies.(HighelevationsofLDHmaysuggestthatthelymphomamayhaverapidprogression,potentiallyrequiringmoreintensivetherapies,butonly25%ofaffectedindividualshaveelevatedLDH.)Advancedimaging(x-ray)techniquescanalsoberecommendedandcanincludeacombinedpositronemissiontomography(PET)andcomputerizedtomography(CT)scanknownasaPET/CTscan.DuringaPETscan,three-dimensionalimagesareproducedtoevaluatehowhealthyandfunctionalcertaintissuesandorgansare.Thisexaminvolvestheuseofaradioactivedrugcalledatracerthatiscombinedwithsugar(glucose).Thisradioactivesugarisinjectedintothebody.Thissugarwillcollectinareasofthebodywherethereisahigherdemandforenergy.Cancerrequirealotofenergytokeepgrowingandspreading,andwillsoakuptheradioactivesugar.TheseareaswillshowuponthePETscanasbrighterthanthesurroundingareas.DuringCTscanning,acomputerandx-raysareusedtocreateafilmshowingcross-sectionalimagesofcertaintissuestructures.ACTscancanshowenlargedorgansorlymphnodes.APET/CTallowsphysicianstoassessthemetabolicandstructural(anatomic)inonesessionandcanreturnamoreaccurateimageorpictureofcancerthaneithertestcanbyitself.AtestknownasfluorescentinsituhybridizationorFISHmayalsobeusedtohelpdiagnosefollicularlymphoma.DuringaFISHexam,probesmarkedbyaspecificcoloroffluorescentdyeareattachedtoaspecificchromosomeallowingresearcherstobetterviewaspecificregionofthatchromosome.Thetestallowsphysicianstodetectalterationsinthegeneticmaterialofchromosomesincludingtranslocationssuchasatranslocationofchromosomes14and18.Thiscanhelpdistinguishfollicularlymphomafromotherformsofindolentlymphoma.AtestcalledpolymerasechainreactionorPCRmayalsobeusedtohelpdiagnosefollicularlymphoma.PCRisatesttechniqueforidentifyingandmakingcopiesofspecificsegmentsofdeoxyribonucleicacid(DNA).ThetestcanidentifytinyamountsofDNAincludinggeneticmaterialtodetectalterationssuchasatranslocationofchromosomes14and18.Thistesttendstobelessreliableindiagnosingfollicularlymphomathanfluorescentinsituhybridization(FISH).StagingWhenanindividualisdiagnosedwithanon-Hodgkinlymphoma(NHL)suchasfollicularlymphoma,assessmentisalsorequiredtodeterminetheextentor“stage”ofthedisease.Stagingisimportanttohelpcharacterizethepotentialdiseasecourseanddetermineappropriatetreatmentapproaches.AvarietyofdiagnostictestsmaybeusedinstagingNHL(e.g.,bloodtests,CTscanning,bonemarrowbiopsy,PETscan).Inaddition,insomepeople,additionalbiopsiesmaybeobtainedtoassistinlymphomastaging.ThespecificstageofNHLmaybebaseduponthenumberoflymphnoderegionsinvolved;whethersuchlymphnodesarelocatedabove,below,oronbothsidesofthediaphragm*;and/orwhetherthemalignancyhasinfiltratedotherlymphatictissues,suchasthespleenorbonemarrow,orspreadtoinvolveotherorgansoutsidethelymphaticsystem,suchastheliver.(*Thediaphragmisthedome-shapedmusclethatseparatesthechestfromtheabdomenandplaysanessentialroleinbreathing.)Althoughvariousstagingsystemshavebeendescribed,asystemcommonlyusedforadultNHListheAnnArborstagingsystem,whichincludesthefollowingstages:StageI–indicatesearly,localizeddiseaseinwhichthemalignancyislimitedtoasinglelymphnoderegionorinasingleorganorregionoutsidethelymphnode(extralymphaticorganorsite).StageII–indicateslocallyadvanceddiseaseinwhichthemalignancyinvolvesmorethanonelymphnoderegionononesideofthediaphragmorisfoundwithinoneextralymphaticorganorsiteanditsregionallymphnoderegion(withorwithoutinvolvementofotherlymphnodesonthesamesideofthediaphragm).StageIII–indicatesadvanceddiseaseinwhichthelymphomainvolveslymphnoderegionsonbothsidesof(i.e.,aboveandbelow)thediaphragmandmayinvolvethespleen.Theremayalsobelocalizedinvolvementofanextralymphaticorganorsite.StageIV–indicateswidespread(disseminated)diseaseinwhichthemalignancyisdiffuselyspreadthroughoutoneormoreextralymphaticorgansorsiteswithorwithoutassociatedlymphnodeinvolvement.FollicularlymphomainthebonemarrowandliverisalwaysstageIV.EachstageofNHLmaybefurtherdividedintocategoriesAorB,baseduponwhetherornotaffectedindividualshavesymptoms.Morespecifically:Aindicatesthatnogeneralized(systemic)symptomsarepresentupondiagnosis.Bindicatesthatanaffectedindividualhasexperienceddrenchingnightsweats,unexplainedfever(above38degreesCelsius),and/orunexplainedweightloss(i.e.,lossofatleast10percentoftotalbodyweightinthesixmonthspriortodiagnosis).Inaddition,categoryEmayindicatethatthemalignancyaffectsasingleorganoutsidethelymphaticsystemorhasspreadfromalymphnodetoanorgan.CategorySmayindicateinvolvementofthespleen.VariousadditionalelementsmaybeconsideredasphysiciansdeterminethestageofNHL,potentialdiseasecourse,andappropriatetreatmentoptions.Suchfactorsmayincludepatientageandgeneralhealth,tumorsize,levelsoftheenzymelactatedehydrogenase,extranodalsiteinvolvement,andotherfactors.StandardTherapiesTreatmentThediagnosisandtherapeuticmanagementoffollicularlymphomamayrequirethecoordinatedeffortsofateamofmedicalprofessionals,suchasphysicianswhospecializeinthediagnosisandtreatmentofcancer(medicaloncologists),disordersofthebloodandblood-formingtissues(hematologists),ortheuseofradiationtotreatcancers(radiationoncologists);oncologynurses;surgeons;dietitians;and/orotherhealthcareprofessionals.Psychosocialsupportfortheentirefamilyisessentialaswell.Geneticcounselingmayberecommendedforaffectedindividualsandtheirfamilies.Thecourseoffollicularlymphomaishighlyvariable.Theaveragesurvivalrateisgreaterthan20years.Someindividualsdonotdevelopsymptomsoronlyrequireonetherapeuticoption,whileotherpeopledevelopsevere,recurrent,andlife-threateningcomplicationsandmayrequirerepeatedandmultipletherapies.Consequently,specifictherapeuticproceduresandinterventionswillvary,dependinguponnumerousfactors,suchasdiseasestage;tumorsize;tumorgrade(whichisrelatedtohowabnormalthetumorcellslookunderamicroscope);thepresenceorabsenceofcertainsymptoms;anindividual’sageandgeneralhealth;and/orotherelements.Decisionsconcerningtheuseofparticulardrugregimensand/orothertreatmentsshouldbemadebyphysiciansandothermembersofthehealthcareteamincarefulconsultationwiththepatientbaseduponthespecificsoftheircase;athoroughdiscussionofthepotentialbenefitsandrisks,includingpossiblesideeffectsandlong-termeffects;patientpreference;andotherappropriatefactors.Therapiesusedtotreatindividualswithfollicularlymphomaincludewatchandwait,radiationtherapy,immunotherapy,single-agentchemotherapyandmultiagentchemotherapy.Inselectindividualswithnosymptomsoffollicularlymphoma(asymptomatic),physiciansmayrecommendwaitingbeforestartingtreatmentuntilthediseaseleadstocertainsymptomsorprogresses.Insuchinstances,thorough,frequentcheckupsarerequiredtoensurethatappropriatetherapiesarebegunwhenthediseasecourseaccelerates.Thisapproachtodiseasemanagementisoftencalled“watchandwait”or“watchfulwaiting.”Mostaffectedindividualseventuallyrequiresystemictreatment.Iffollicularlymphomaisdetectedearlyenough,someaffectedindividualsmaybetreatedwithradiationtherapy,inwhichradiationisusedtodestroycanceroustissue.Radiationtherapyoftenproducesprolongedperiodsofremissioninindividualsinearlystage(tageI)diseaseandisfrequentlyusedforindividualswithearlystagedisease.Mostaffectedindividualsarediagnosedwithadvanceddisease.AdvanceddiseaseincludesindividualswithstageIIIorIVdisease(seeStagingabove).Affectedindividualsreceivetreatmentregimensthatincludeamedicationknownasananti-CD20monoclonalantibody.Amonoclonalantibodyisatypeofimmunetherapy;itusestheimmunesystemtohelpfightoffcancer.CD20isasubstancefoundonthesurfaceofB-cells.Anti-CD20monoclonalantibodiesaremedicationsthattargetCD20and,therefore,targettheB-cellsinthebody,includingthecancerousB-cellsthatmakeupfollicularlymphoma.Twotypesofanti-CD20monoclonalantibodiesareusedtotreatadultswithfollicularlymphomaandareknownasrituximab(Rituxan®)andobinutuzumab(Gazyva®).In1997,theU.S.FoodandDrugAdministration(FDA)approvedrituximab(Rituxan®)forthetreatmentofindividualswithfollicularlymphomathatdidnotrespondtoothertreatments(refractory)orreturnedaftertreatment(relapsed).In2006,rituximabwasapprovedasafirst-linetherapyforaffectedindividuals.Rituximabcanbeusedalone(asasingleagent)asasingle-agenttherapy.Inindividualswithbulkierdiseaseorwhorequireamorerapidresponse(oftenduetospecificsymptomsormanifestations),rituximabisusedaspartofadrugregimen(multiagentchemotherapy)thatincludesothermoretraditionalchemotherapeuticdrugs.ThetwomostpopularchemotherapeuticregimensusedforfollicularlymphomaarebendamustineplusrituximabandCHOP-R.CHOP-RisacommonchemotherapeuticregimenusedtotreatNHLandincludescyclophosphamide,doxorubicinhydrochloride,vincristinesulfate,andprednisonegivenalongwithrituximab.Sometimes,othermedicationsmaybetriedalongwithrituximabincludingchlorambucil(Leukeran®)orlenalidomide(Revlimid®).In2017,theFDAapprovedobinutuzumab(Gazyva®)alongwithchemotherapyforthetreatmentofpreviouslyuntreatedindividualswithstageIIbulky,stageIII,orstageIVfollicularlymphoma.Whilesomeindividualswithfollicularlymphomaarecured,themajorityofaffectedindividualswillnotbecuredwithinitialorfollowuptherapy.Follicularlymphomaoftenrecurs(relapses).Affectedindividualsrequiremaintenancetherapy.Maintenancetherapyisdesignedtohelpmaintaintheeffectivenessofaprimarytherapyinordertokeepcancerinremission(i.e.preventarelapse)andtohelpminimizesideeffectsoftherapy.Bothrituximabandobinutuzumabcanbeusedformaintenancetherapy.Rituximabandobinutuzumabcanalsobeusedtotreatfollicularlymphomawhenthecancerreturnsaftertreatment(relapse),orwhenthecancerdoesnotrespondtoanothertypeoftreatment(refractory).Thereareadditionalmedicationsthathavebeenapprovedforthetreatmentofrelapsedorrefractorylymphoma.In2014,theFDAapprovedthedrug,idelalisib(Zydelig®),forthetreatmentofadultswithfollicularlymphomawhohavereceivedatleasttwoothertherapies.TheFDAhasalsoapprovedthedrugcopanlisib(Aliqopa®)forthetreatmentofadultswithrelapsedfollicularlymphomawhohavereceivedatleasttwoothersystemictreatments.Idelalisibandcopanlisibaredrugsthatinhibitorblockthatactivityofaproteincalledphosphoinositide3-kinase.Thisproteinplaysaroleintheactivation,growthandspread,andsurvivalofB-cells.Radioimmunotherapyisalsousedtotreatrelapsedorrefractoryfollicularlymphoma.Radioimmunotherapyusesradiationalongwithcancer-specificantibodiestoattackcancercells.Ibritumomabtiuxetan(Zevalin®)isamonoclonalantibodyradioimmunotherapythatwasapprovedbytheFDAin2002forthetreatmentofrelapsedorrefractory,low-grade,follicularortransformedB-celllymphoma.Ibritumomabtiuxetanhasalsobeenusedasthesoleinitialtherapyforsomepeople.InvestigationalTherapiesResearchersarestudyingchemotherapywithautologousorallogeneichematopoieticstemcelltransplantation(HSCT)forthetreatmentofindividuals,particularlyyoungerindividuals,whohaverelapsedorrefractoryfollicularlymphoma.Affectedindividualsundergohigh-dosesofchemotherapy(oftenRituxantherapy)followedbyanautologousstemcelltransplant.Stemcellsarespecialcellsfoundinbonemarrowthatmanufacturedifferenttypesofbloodcells(e.g.,redbloodcells,platelets).Inautologousstemcelltransplantation,anaffectedindividual’sstemcellsareremovedafterpriortreatment.Thesehealthystemcellsarelaterre-infusedintothebonemarrowtorestorethechild’simmunesystemthatwasdamagedbytheintensechemotherapy.Inallogenicstemcelltransplantation,affectedindividuals,aftertreatmentwithchemotherapy,receivehematopoieticstemcellsfromahealthydonor.Thesearemajormedicalproceduresthatcarriessignificantrisk.Generally,HSCTisreservedforindividuals,usuallyyoungerindividuals,withrefractoryandsometimesrelapsedfollicularlymphoma.Researchindicatesthatthesetreatmentscanleadtolong-lastingremissionandpotentiallyevenacureinsomepeople.Affectedindividualstransplantedintheirfirstorsecondrelapsehaveabetterprognosisthanindividualstreatedlaterinthecourseofthedisease.Moreresearchisnecessarytodeterminethelong-termsafetyandeffectivenessofthistherapy.Researchisunderwaytodevelopadditionalanti-CD20monoclonalantibodiesfortreatingfollicularlymphoma.Thesemedicationswouldbeforindividualswhodidnotrespondtotherapywithrituximaborobinutuzumab,orcouldnottoleratethosemedications,orthatmayprovemoreeffective.Additionalmedicationsthatarebeingstudiedforrelapsedfollicularlymphomaincludeibrutinib(Imbruvica®),lenalidomide(Revlimid®),BCL-2inhibitors,andinhibitorsofprogrammedcelldeathprotein1(PD1)orPD1ligand1(PDL1).Moreresearchisnecessarytodeterminethelong-termsafetyandeffectivenessofthesetherapies.Drugsarealsobeingstudiedthatcanstimulatetheimmunesystemtoactinordertoenhancetheeffectivenessofrituximab.Thesedrugsaresometimescalledimmunostimulatorydrugs.InformationoncurrentclinicaltrialsispostedontheInternetathttps://clinicaltrials.gov/.AllstudiesreceivingU.S.Governmentfunding,andsomesupportedbyprivateindustry,arepostedonthisgovernmentwebsite.ForinformationaboutclinicaltrialsbeingconductedattheNIHClinicalCenterinBethesda,MD,contacttheNIHPatientRecruitmentOffice:Toll-free:(800)411-1222TTY:(866)411-1010Email:[email protected]SomecurrentclinicaltrialsalsoarepostedonthefollowingpageontheNORDwebsite:https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/Forinformationaboutclinicaltrialssponsoredbyprivatesources,contact:http://www.centerwatch.com/ForinformationaboutclinicaltrialsconductedinEurope,contact:https://www.clinicaltrialsregister.eu/NORDMemberOrganizationsNORD’s®RareCancerCoalition®(RCC)1779MassachusettsAvenueNWSte500Washington,DC20036USAPhone:(202)545-3971Email:[email protected]Website:https://rarediseases.org/get-involved/rare-cancer-coalition/OtherOrganizationsAmericanCancerSociety,Inc.250WilliamsNWStSte6000Atlanta,GA30303USAPhone:(404)320-3333Toll-free:(800)227-2345Website:http://www.cancer.orgCancerCare,Inc.275SeventhAvenueNewYork,NY10001Phone:(212)712-8400Toll-free:(800)813-4673Email:[email protected]Website:http://www.cancercare.orgCancerHopeNetwork2NorthRoadSuiteAChester,NJ07930Phone:(908)879-4039Toll-free:(800)552-4366Email:[email protected]Website:http://www.cancerhopenetwork.orgFriendsofCancerResearch1800MStreetNWSuite1050SouthWashington,DC20036Phone:(202)944-6700Email:[email protected]Website:http://www.focr.orgInternationalCancerAllianceforResearchandEducation(ICARE)4853CordellAvenueSuite14Bethesda,MD20814Phone:(301)656-3461Toll-free:(800)422-7361Email:[email protected]Website:http://www.icare.orgLeukemia&LymphomaSociety3InternationalDriveSuite200RyeBrook,NY10573Phone:(914)949-5213Toll-free:(800)955-4572Email:[email protected]Website:http://www.LLS.orgLymphomaAction(UK)3CromwellCourtNewStreetAylesbury,BucksHP202PBUnitedKingdomPhone:00441296619400Email:[email protected]Website:https://lymphoma-action.org.uk/LymphomaCanada6860CenturyAvenue#202Mississauga,L5N2W5CanadaPhone:(905)858-5967Toll-free:(866)659-5556Email:[email protected]Website:http://www.lymphoma.caLymphomaResearchFoundationWallStreetPlaza88PineStreet,Suite2400NewYork,NY10005USAPhone:(212)349-2910Toll-free:(800)500-9976Email:[email protected]Website:http://www.lymphoma.orgNationalCancerInstitute6116ExecutiveBlvdSuite300Bethesda,MD20892-8322USAPhone:(301)435-3848Toll-free:(800)422-6237Email:[email protected]Website:http://www.cancer.govNationalCancerInstitutePhysicianDataQueryOfficeofCommunicationsandEducationPublicInquiriesOfficeBethesda,MD20892-8322Toll-free:(800)422-6237Email:[email protected]Website:http://www.cancer.gov/cancertopics/pdq/cancerdatabaseNIH/NationalInstituteofAllergyandInfectiousDiseasesNIAIDOfficeofCommunicationsandGovernmentRelations5601FishersLane,MSC9806Bethesda,MD20892-9806Phone:(301)496-5717Toll-free:(866)284-4107Email:[email protected]Website:http://www.niaid.nih.gov/OncoLink:TheUniversityofPennsylvaniaCancerCenterResource3400CivicCenterBlvdSuite2338Philadelphia,PA19104USAPhone:(215)349-8895Email:[email protected]Website:https://www.oncolink.org/RareCancerAlliance405HollyStreetGoodrich,TX77335USAWebsite:http://www.rare-cancer.orgReferencesJOURNALARTICLESFreedmanA.Follicularlymphoma:2018updateondiagnosisandmanagement.AmJHematol.2018;93:296-305.https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.24937Diagnosisandtreatmentoffollicularlymphoma:anupdated.SwissMedWkly.2018;148:w14635.https://smw.ch/article/doi/smw.2018.14635LeeHJ,BangCH,LeeJH,ParkYM,LeeJY.Pediatricfollicularlymphoma:ararevariant.AnnDermatol.2018;30:489-490.https://www.ncbi.nlm.nih.gov/pubmed/30065597StennerF,RennerC.Cancerimmunotherapyandtheimmuneresponseinfollicularlymphoma.FrontOncol.2018;8:219.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020779/FalchiL,FerrajoliA,JacobsI,Nava-ParadaP.Anevidence-basedreviewofanti-CD20antibody-containingregimensforthetreatmentofpatientswithrelapsedorrefractorychroniclymphocyticleukemia,diffuselargeB-celllymphoma,follicularlymphoma.ClinLymphomaMyelomaLeuk.2018;18:508-518.https://www.ncbi.nlm.nih.gov/pubmed/29934061ArmitageJO,GascoyneRD,LunningMA,CavalliF.Non-Hodgkinlymphoma.Lancet.2017;390:298-310.https://www.ncbi.nlm.nih.gov/pubmed/28153383ArmitageJO,LongoDL.Whichanti-CD20antibodyisbetterinfollicularlymphoma.NEnglJMed.2017;377:1389-1390.https://www.ncbi.nlm.nih.gov/pubmed/28976852SchmidtJ,GongS,MarafiotiT,etal.Genome-wideanalysisofpediatric-typefollicularlymphomarevealslowgeneticcomplexityandrecurrentalterationsofTNFSF14gene.Blood.2016;128:1101-1111.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000845/LouissaintAJr.,SchafernakKT,GeyerJT,etal.Pediatric-typenodalfollicularlymphoma:abiologicallydistinctlymphomawithfrequentMAPKpathwaymutations.Blood.2016;128:1093-1100.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000844/KahlBS,YangDT.Follicularlymphoma:evolvingtherapeuticstrategies.Blood.2016;127:2055-2063.https://www.ncbi.nlm.nih.gov/pubmed/26989204IwamuroM,KondoE,TakataK,YoshinoT,OkadaH.Diagnosisoffollicularlymphomaofthegastrointestinaltract:abetterinitialdiagnosticworkup.WorldJGastroenterol.2016;22:1674-1683.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721998/TefferiA,FreedmanAS.CMEInformation:Follicularlymphoma:2015updateondiagnosisandmanagement.AmJHematol.2015;90:1171-1178.https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.24200JacobsonCA,FreedmanAS.Isobservationdeadinfollicularlymphoma?Stillappropriate.JNatlComprCancNetw.2015;13:367-370.http://www.jnccn.org/content/13/3/367.longMamessierE,Broussais-GuillaumotF,ChetailleB,etal.Natureandimportanceoffollicularlymphomaprecursors.Haematologica.2014;99:802-810.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008113/TakataK,Miyata-TakataT,SatoY,YoshinoT.Pathologyoffollicularlymphoma.JClinExpHematop.2014;54:3-9.https://www.ncbi.nlm.nih.gov/pubmed/24942941MamessierE,SongJY,EberleFC,etal.Earlylesionsoffollicularlymphoma:ageneticperspective.Haematologica.2014;99:481-488.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943311/BodorC,GrossmanV,PopovN,etal.EZH2mutationsarefrequentandrepresentanearlyeventinfollicularlymphoma.Blood.2013;122:3165-3168.https://www.ncbi.nlm.nih.gov/pubmed/24052547McNamaraC,DaviesJ,DyerM,etalGuidelinesontheinvestigationandmanagementoffollicularlymphoma.BrJHaematol.2012;156:446-467.https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2011.08969.xOschliesI,SalaverriaI,MahnF,etal.Pediatricfollicularlymphoma–aclinic-pathologicalstudyofapopulation-basedseriesofpatientstreatedwiththeNon-Hodgkin’sLymphoma–Berlin–Frankfurt–Munster(NHL-BFM)multicentertrials.Haematologica.2010;95:253-259.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817028/AgrawalR,WangJ.Pediatricfollicularlymphoma:arareclinicopathologicentity.ArchPatholLabMed.2009;133:142-146.https://www.ncbi.nlm.nih.gov/pubmed/19123728SchmatzAI,SteubelB,Kretschmer-ChottE,etal.Primaryfollicularlymphomaoftheduodenumisadistinctmucosal/submucosalvariantoffollicularlymphoma:aretrospectivestudyof63cases.JClinOncol.2011;29:1445-1451.https://www.ncbi.nlm.nih.gov/pubmed/21383289INTERNETFreedmanAS,AsterJC.Clinicalmanifestations,pathologicfeatures,diagnosisandprognosisoffollicularlymphoma.UpToDate,Inc.Apr11,2019.Availableat:https://www.uptodate.com/contents/clinical-manifestations-pathologic-features-diagnosis-and-prognosis-of-follicular-lymphomaAccessedMay2,2019.FreedmanAS,FriedbergJW.Treatmentofrelapsedorrefractoryfollicularlymphoma.UpToDate,Inc.Apr11,2019.Availableat:https://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-follicular-lymphoma?search=follicularAccessedMay2,2019.FreedmanAS,FriedbergJW.Treatmentofadvancedstage(III/IV)follicularlymphoma.UpToDate,Inc.Mar11,2019.Availableat:https://www.uptodate.com/contents/initial-treatment-of-advanced-stage-iii-iv-follicular-lymphomaAccessedMay2,2019.YearsPublished2019TheinformationinNORD’sRareDiseaseDatabaseisforeducationalpurposesonlyandisnotintendedtoreplacetheadviceofaphysicianorotherqualifiedmedicalprofessional.ThecontentofthewebsiteanddatabasesoftheNationalOrganizationforRareDisorders(NORD)iscopyrightedandmaynotbereproduced,copied,downloadedordisseminated,inanyway,foranycommercialorpublicpurpose,withoutpriorwrittenauthorizationandapprovalfromNORD.Individualsmayprintonehardcopyofanindividualdiseaseforpersonaluse,providedthatcontentisunmodifiedandincludesNORD’scopyright.NationalOrganizationforRareDisorders(NORD)55KenosiaAve.,DanburyCT06810•(203)744-0100ReportIndexSubdivisionsGeneralDiscussionSigns&SymptomsCausesAffectedPopulationsRelatedDisordersStandardTherapiesInvestigationalTherapiesSupportingOrganizationsReferencesRelatedContentNORDPatientAssistanceNORDstrivestoopennewassistanceprogramsasfundingallows.Ifwedon'thaveaprogramforyounow,pleasecontinuetocheckbackwithus.LearnMore>NORDVideo:RareDiseaseFactsNORDProgramAlonewearerare.Togetherwearestrong.®SignUpforNORDNews!FollowNORD×