Non-Hodgkin Lymphomas - Hematology and Oncology

Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, ... MSDManual Pleaseconfirmthatyouareahealthcareprofessional Yes No LeavethisSite? Thelinkyouhaveselectedwilltakeyoutoathird-partywebsite.Wedonotcontrolorhaveresponsibilityforthecontentofanythird-partysite. 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MedicalTopics&Chapters 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 Z Professional / HematologyandOncology / Lymphomas / ... / Non-HodgkinLymphomas / OTHERTOPICSINTHISCHAPTER OverviewofLymphoma HodgkinLymphoma Non-HodgkinLymphomas BurkittLymphoma CutaneousT-cellLymphomas(CTCL) Non-HodgkinLymphomas By PeterMartin ,MD,WeillCornellMedicine; JohnP.Leonard ,MD,WeillCornellMedicine Lastfullreview/revisionMay2022|ContentlastmodifiedSep2022 ClickhereforPatientEducation Etiology Pathophysiology Classification SymptomsandSigns Diagnosis Prognosis Treatment KeyPoints MoreInformation TopicResources 3DModels(0) Audios(0) Calculators(0) Images(2) Non-HodgkinLymphoma(Cervical... Non-HodgkinLymphoma(Posterior... LabTest(0) Tables(1) LuganoStagingofHodgkin... 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Non-Hodgkinlymphomasareaheterogeneousgroupofdisordersinvolvingmalignantmonoclonalproliferationoflymphoidcellsinlymphoreticularsites,includinglymphnodes,bonemarrow,thespleen,theliver,andthegastrointestinaltract.Presentingsymptomsusuallyincludeperipherallymphadenopathy.However,somepatientspresentwithoutlymphadenopathybutwithabnormallymphocytesincirculation.Diseaseislikelytobedisseminatedatthetimeofpresentation,anddiagnosisisusuallybasedonlymphnodeorbonemarrowbiopsyorboth.Managementstrategiesmayincludewatchandwait,chemotherapy,targeteddrugs(eg,kinaseinhibitors),andimmunotherapies(eg,monoclonalantibodies,chimericantigenreceptorTcells);occasionally,radiationtherapyisadded.Withfewexceptions,stemcelltransplantationisusuallyreservedforpatientswithaggressivelymphomasafterincompleteremissionorrelapse.(SeealsoOverviewofLymphomaOverviewofLymphomaLymphomasareaheterogeneousgroupoftumorsarisinginthereticuloendothelialandlymphaticsystems.ThemajortypesareHodgkinlymphomaNon-HodgkinlymphomaSeetableComparisonofHodgkin...readmore.)Non-HodgkinlymphomaismorecommonthanHodgkinlymphomaHodgkinLymphomaHodgkinlymphomaisalocalizedordisseminatedmalignantproliferationofcellsofthelymphoreticularsystem,primarilyinvolvinglymphnodetissue,spleen,liver,andbonemarrow.Symptoms...readmore.Itisthe6thmostcommoncancerintheUSandrepresents4%ofallnewcancersintheUSeachyearand3%ofallcancerdeaths.Over80,000newcasesarediagnosedannuallyinallagegroupsandthereareabout20,000deaths.Non-Hodgkinlymphomaisnotonediseasebutratheracategoryoflymphocytecancerswithanumberofsubgroupslargelydividedintoaggressiveandindolenttypes.Incidenceincreaseswithage(medianage,67years).EtiologyofNon-HodgkinLymphomasThecauseofnon-Hodgkinlymphomaisunknown,although,aswiththeleukemiasOverviewofLeukemiaLeukemiaisamalignantconditioninvolvingtheexcessproductionofimmatureorabnormalleukocytes,whicheventuallysuppressestheproductionofnormalbloodcellsandresultsinsymptoms...readmore,substantialevidencesuggestsaviralcause(eg,humanT-cellleukemia-lymphomavirus,Epstein-BarrvirusInfectiousMononucleosisInfectiousmononucleosisiscausedbyEpstein-Barrvirus(EBV,humanherpesvirustype4)andischaracterizedbyfatigue,fever,pharyngitis,andlymphadenopathy.Fatiguemaypersistweeksor...readmore,hepatitisBvirusHepatitisB,ChronicHepatitisBisacommoncauseofchronichepatitis.Patientsmaybeasymptomaticorhavenonspecificmanifestationssuchasfatigueandmalaise.Diagnosisisbyserologictesting.Withouttreatment...readmore,hepatitisCvirusHepatitisC,ChronicHepatitisCisacommoncauseofchronichepatitis.Itisoftenasymptomaticuntilmanifestationsofchronicliverdiseaseoccur.Diagnosisisconfirmedbyfindingpositiveanti-HCVandpositive...readmore,HIVHumanImmunodeficiencyVirus(HIV)InfectionHumanimmunodeficiencyvirus(HIV)infectionresultsfrom1of2similarretroviruses(HIV-1andHIV-2)thatdestroyCD4+lymphocytesandimpaircell-mediatedimmunity,increasingriskofcertain...readmore,humanherpesvirus8OverviewofHerpesvirusInfectionsEighttypesofherpesvirusesinfecthumans(seeTable:HerpesvirusesThatInfectHumans).Afterinitialinfection,allherpesvirusesremainlatentwithinspecifichostcellsandmaysubsequently...readmore)insomecases.Helicobacterpyloriinfectionalsoincreaseslymphomarisk.Patientsatincreasedriskofnon-HodgkinlymphomaincludethosewithPrimaryimmunodeficiencyPrimaryImmunodeficienciesImmunodeficiencydisordersareassociatedwithorpredisposepatientstovariouscomplications,includinginfections,autoimmunedisorders,andlymphomasandothercancers.Primaryimmunodeficiencies...readmoreSecondaryimmunodeficiencySecondaryImmunodeficienciesImmunodeficiencydisordersareassociatedwithorpredisposepatientstovariouscomplications,includinginfections,autoimmunedisorders,andlymphomasandothercancers.Primaryimmunodeficiencies...readmore(eg,wheninducedbyimmunosuppressivedrugs,suchasthoseusedinrheumatologicdisordersandpost-solidorgantransplant)Exposuretocertainchemicals(eg,someherbicidesandinsecticides)ChronicinflammationandreactivelymphnodehyperplasiaNon-Hodgkinlymphomaisthe2ndmostcommoncancerinHIV-infectedpatientsNon-HodgkinlymphomaAIDS-definingcancersinHIV-infectedpatientsareKaposisarcomaLymphoma,Burkitt(orequivalentterm)Lymphoma,immunoblastic(orequivalentterm)Lymphoma,primary,ofcentralnervoussystemreadmore,andsomeAIDSpatientspresentwithlymphoma.Indeed,patientswithnon-HodgkinlymphomashouldgenerallybescreenedforHIVandhepatitisviruses.Geneticfactorsappeartoplayarole.Recentevidenceshowsthatcertainsinglenucleotidepolymorphismsincreasetheriskoflymphoma.Also,patientswithafirst-degreerelativewithHodgkinornon-Hodgkinlymphomahaveanincreasedriskofnon-Hodgkinlymphoma.PathophysiologyofNon-HodgkinLymphomasMost(80to85%)non-HodgkinlymphomasarisefromBlymphocytes;theremainderarisefromTlymphocytesornaturalkillercells.Thestageoflymphocytedifferentiationatwhichtheoncogeniceventoccursdeterminesthediseasepresentationandoutcome.Mostlymphomasarenodalwithvariableinvolvementofthebonemarrowandperipheralblood.Aleukemia-likepicturewithperipherallymphocytosisandbonemarrowinvolvementmaybepresentinupto50%ofchildrenandabout20%ofadultswithsometypesofnon-Hodgkinlymphoma.Hypogammaglobulinemiacausedbyaprogressivedecreaseinimmunoglobulinproductionispresentin15%ofpatientsatdiagnosis.Hypogammaglobulinemiaincreasestheriskofseriousbacterialinfection,andpatientsmayrequireIVimmuneglobulintoreplacedeficientimmunoglobulins.Pearls&PitfallsThereisconsiderableoverlapbetweennon-Hodgkinlymphomaandleukemia;bothmayhaveperipherallymphocytosisandbonemarrowinvolvement.ClassificationofNon-HodgkinLymphomasPathologicclassificationofnon-Hodgkinlymphomacontinuestoevolve,reflectingnewinsightsintothecellsoforiginandthebiologicbasesoftheseheterogeneousdiseases.The2016WHOclassificationisvaluablebecauseitincorporatesimmunophenotype,genotype,andcytogenetics,butnumerousothersystemsexist(eg,Lyonclassification).Non-Hodgkinlymphomasarecommonlyalsocategorizedasindolentoraggressive:Indolent:SlowlyprogressiveandresponsivetotherapybutnottypicallycurablewithstandardapproachesAggressive:RapidlyprogressivebutresponsivetochemotherapyandoftencurableInchildren,non-Hodgkinlymphomaisalmostalwaysaggressive.Follicularandotherindolentlymphomasareunusual.Thetreatmentoftheseaggressivelymphomas(BurkittBurkittLymphomaBurkittlymphomaisanaggressiveB-cellnon-Hodgkinlymphomaoccurringinchildrenandadults.Endemic(African),sporadic(non-African),andimmunodeficiency-relatedformsexist.(Seealso...readmore,diffuselargeBcell,andlymphoblasticlymphoma)presentsspecialconcerns,includinggastrointestinaltractinvolvement(particularlyintheterminalileum);meningealspread(requiringcerebrospinalfluidprophylaxisortreatment);andothersanctuarysitesofinvolvement(eg,testes,brain).Inaddition,withthesepotentiallycurablelymphomas,treatmentofadverseeffectsaswellasoutcomemustbeconsidered,includinglaterisksofsecondarycancer,cardiorespiratorysequelae,fertilitypreservation,anddevelopmentalconsequences.SymptomsandSignsofNon-HodgkinLymphomasMostpatientspresentwithAsymptomaticperipherallymphadenopathyEnlargedlymphnodescanberubberyanddiscreteandlatercoalesceintomasses.Affectednodesareusuallynotpainful,unlikethetendernodesthatoftenoccurwithviralinfections.Nodalinvolvementislocalizedinsomepatients,butmostpatientshaveseveralareasaffected.Theinitialphysicalexaminationshouldcarefullylookfornodesinthecervical,axillary,inguinal,andfemoralregions.Insomepatients,enlargedmediastinalandretroperitonealnodespressonnearbystructures,leadingtosymptoms.ThemostimportantoftheseareCompressionofthesuperiorvenacava(SVC):Shortnessofbreathandfacialedema(SVCsyndromeRegionalspread)Compressionoftheexternalbiliarytree:JaundiceCompressionoftheureters:HydronephrosisBowelobstruction:VomitingandobstipationInterferencewithlymphdrainage:ChylouspleuralorperitonealfluidorlymphedemaofalowerextremityTheskinisinvolvedinsomenon-Hodgkinlymphomas.B-cellnon-Hodgkinlymphomacanaffectthescalp(follicularnon-Hodgkinlymphoma)orthelegs(largecellnon-Hodgkinlymphoma),typicallycausingslightlyraised,erythematousnodules.IncutaneousT-cellnon-Hodgkinlymphoma,skinlesionscanbediffuse,nonpalpableerythemaordiscretepapules,plaques,ortumors.Systemicsymptoms(eg,fatigueFatigueFatigueoccursmostoftenaspartofasymptomcomplex,butevenwhenitisthesoleormainpresentingsymptom,fatigueisoneofthemostcommonsymptoms.Fatigueisdifficultyinitiating...readmore,fevers,nightsweats,weightlossInvoluntaryWeightLossInvoluntaryweightlossgenerallydevelopsoverweeksormonths.Itcanbeasignofasignificantphysicalormentaldisorderandisassociatedwithanincreasedriskformortality.Thecausative...readmore)canbethefirstmanifestationsinsomepatients,mostcommonlyinaggressivelymphomas.Thesepatientsmaynothavenoticedlymphadenopathyornothaveexternal,palpabledisease;thesepatientsrequireCTorpositronemissiontomography(PET)imagingtodiscoverthelesion(s).Anemiaisinitiallypresentinsomepatientsandeventuallydevelopsinmany.Itmaybecausedbybleedingduetogastrointestinallymphoma,withorwithoutlowplateletlevels;hemolysisduetohypersplenismorCoombs’-positivehemolyticanemia;bonemarrowinfiltrationduetolymphoma;orbonemarrowsuppressionduetochemotherapyorradiationtherapy.ManifestationsofsomespecificlymphomasAdultT-cellleukemia-lymphoma,whichisassociatedwithhumanT-lymphotropicvirus1(HTLV-1),hasafulminatingclinicalcoursewithskininfiltrates,lymphadenopathy,hepatosplenomegaly,andleukemiaOverviewofLeukemiaLeukemiaisamalignantconditioninvolvingtheexcessproductionofimmatureorabnormalleukocytes,whicheventuallysuppressestheproductionofnormalbloodcellsandresultsinsymptoms...readmore.TheleukemiccellsaremalignantTcells,manywithconvolutednuclei.HypercalcemiaHypercalcemiaHypercalcemiaisatotalserumcalciumconcentration>10.4mg/dL(>2.60mmol/L)orionizedserumcalcium>5.2mg/dL(>1.30mmol/L).Principalcausesincludehyperparathyroidism,vitamin...readmoreoftendevelops,relatedtohumoralfactorsratherthantodirectboneinvasion.Anaplasticlargecelllymphomamaycauserapidlyprogressiveskinlesions,adenopathy,andviscerallesions.ThisdiseasemaybemistakenforHodgkinlymphomaHodgkinLymphomaHodgkinlymphomaisalocalizedordisseminatedmalignantproliferationofcellsofthelymphoreticularsystem,primarilyinvolvinglymphnodetissue,spleen,liver,andbonemarrow.Symptoms...readmoreormetastaticundifferentiatedcarcinoma.DiagnosisofNon-HodgkinLymphomasLymphnodebiopsyOftenunilateralbonemarrowaspirationandbiopsyFDG-PET/CTofchest,abdomen,andpelvisforstagingMRIofbrainand/orspinalcordifneurologicsymptomsarepresentAswithHodgkinlymphoma,non-HodgkinlymphomaisusuallysuspectedinpatientswithPainlesslymphadenopathyAdenopathydetectedonachestx-rayorCTdoneforotherreasonsPainlesslymphadenopathycanalsoresultfrominfectiousmononucleosisInfectiousMononucleosisInfectiousmononucleosisiscausedbyEpstein-Barrvirus(EBV,humanherpesvirustype4)andischaracterizedbyfatigue,fever,pharyngitis,andlymphadenopathy.Fatiguemaypersistweeksor...readmore,toxoplasmosisToxoplasmosisToxoplasmosisisinfectionwithToxoplasmagondii.Symptomsrangefromnonetobenignlymphadenopathy,amononucleosis-likeillness,tolife-threateningcentralnervoussystem(CNS)disease...readmore,cytomegalovirusinfectionCytomegalovirus(CMV)InfectionCytomegalovirus(CMV,humanherpesvirustype5)cancauseinfectionsthathaveawiderangeofseverity.Asyndromeofinfectiousmononucleosisthatlacksseverepharyngitisiscommon.Severe...readmore,primaryHIVinfectionHumanImmunodeficiencyVirus(HIV)InfectionHumanimmunodeficiencyvirus(HIV)infectionresultsfrom1of2similarretroviruses(HIV-1andHIV-2)thatdestroyCD4+lymphocytesandimpaircell-mediatedimmunity,increasingriskofcertain...readmore,orleukemiaOverviewofLeukemiaLeukemiaisamalignantconditioninvolvingtheexcessproductionofimmatureorabnormalleukocytes,whicheventuallysuppressestheproductionofnormalbloodcellsandresultsinsymptoms...readmore.Similarchestx-rayfindingscanresultfromlungcarcinomaLungCarcinomaLungcarcinomaistheleadingcauseofcancer-relateddeathworldwide.About85%ofcasesarerelatedtocigarettesmoking.Symptomscanincludecough,chestdiscomfortorpain,weightloss...readmore,sarcoidosisSarcoidosisSarcoidosisisaninflammatorydisorderresultinginnoncaseatinggranulomasinoneormoreorgansandtissues;etiologyisunknown.Thelungsandlymphaticsystemaremostoftenaffected,but...readmore,ortuberculosisTuberculosis(TB)Tuberculosisisachronic,progressivemycobacterialinfection,oftenwithanasymptomaticlatentperiodfollowinginitialinfection.Tuberculosismostcommonlyaffectsthelungs.Symptomsinclude...readmore.Lesscommonly,patientspresentafterafindingofperipherallymphocytosisonacompletebloodcount(CBC)donefornonspecificsymptoms.Insuchcases,thedifferentialdiagnosisincludesleukemiaOverviewofLeukemiaLeukemiaisamalignantconditioninvolvingtheexcessproductionofimmatureorabnormalleukocytes,whicheventuallysuppressestheproductionofnormalbloodcellsandresultsinsymptoms...readmore,Epstein-BarrvirusinfectionInfectiousMononucleosisInfectiousmononucleosisiscausedbyEpstein-Barrvirus(EBV,humanherpesvirustype4)andischaracterizedbyfatigue,fever,pharyngitis,andlymphadenopathy.Fatiguemaypersistweeksor...readmore,andDuncansyndrome(X-linkedlymphoproliferativesyndromeX-linkedLymphoproliferativeSyndromeX-linkedlymphoproliferativesyndromeresultsfromaT-cellandnaturalkillercelldefectandischaracterizedbyanabnormalresponsetoEpstein-Barrvirusinfection,leadingtoliverfailure...readmore).Testsneededtomakethediagnosisarefollowedbyteststocompletestagingandassessetiologyandprognosis(1DiagnosisreferenceNon-Hodgkinlymphomasareaheterogeneousgroupofdisordersinvolvingmalignantmonoclonalproliferationoflymphoidcellsinlymphoreticularsites,includinglymphnodes,bonemarrow,the...readmore).DiagnostictestsEnlargedlymphnodesarebiopsied.Ifanodeispalpable,noimagingisrequiredinitially,althoughCTorultrasonographymaybeneededtoproperlyplansubsequenttests.Ifthelesioniseasilypalpable,anopenbiopsyispreferred.Ifthelesionisinthelungorabdomen,acoreneedlebiopsy(18-to20-gaugeneedle)doneusingCTorultrasoundguidancecanoftenobtainanadequatespecimenfordiagnosis.Afineneedlebiopsy(percutaneousorbronchoscopic)frequentlywillnotproduceadequatetissue,especiallyforinitialdiagnosis;corebiopsyispreferredifdeemedsafe.Biopsiesshouldbereviewedbyapathologistwithexpertiseinlymphomadiagnosissothatthelymphomacanbecorrectlyclassified.Ifthisreviewisnotavailablelocally,theslidesshouldbesenttoareferencelaboratorywithhematopathologyexpertise.Theproperclassificationofnon-Hodgkinlymphomaiscriticalfortreatmentplanning.Non-Hodgkinlymphomasarepotentiallycurable,butwithoutaprecisediagnosis,optimaltherapymaynotbechosen.Histologiccriteriaonbiopsyincludedestructionofnormallymphnodearchitectureandinvasionofthecapsuleandadjacentfatbycharacteristicneoplasticcells.Immunophenotypingstudiestodeterminethecelloforiginareofgreatvalueinidentifyingspecificsubtypesandhelpingdefineprognosisandmanagement;thesestudiesalsocanbedoneonperipheralcellsiftheyarepresent,buttypicallythesestainsareappliedtoformalin-fixed,paraffin-embeddedtissue.DemonstrationoftheleukocytecommonantigenCD45byimmunoperoxidaserulesoutmetastaticcancer,whichisofteninthedifferentialdiagnosisof“undifferentiated”cancers.Thetestforleukocytecommonantigen,mostsurfacemarkerstudies,andgenerearrangement(todocumentB-cellorT-cellclonality)canbedoneonfixedtissues.Cytogeneticsandflowcytometryrequirefreshtissue.StagingtestsOncethediagnosisoflymphomaismade,stagingtestsaredone.Acombinedfluorodeoxyglucose(FDG)-PET/CTscanofthechest,abdomen,andpelvisisrecommended.PET/CTprovidesaccuratelocationoflesions,theirsize(fromCT)andtumormetabolism(fromFDG-PET).IfcombinedFDG-PET/CTisnotavailable,acontrast-enhancedCTscanofthechest,abdomen,andpelvisisdone.Unilateralbonemarrowaspirationandbiopsyisoftendoneinpatientswithnon-Hodgkinlymphoma.Bonemarrowassessmentinlow-grade(indolent)non-HodgkinlymphomaorT-cellnon-Hodgkinlymphomacanbelimitedtocaseswherefindingswillchangemanagementorareneededtoassesscytopenias.TestingforcomplicationsandprognosisBloodteststypicallyincludecompletebloodcountwithwhitebloodcelldifferential,kidneyfunctionandlivertests(includingserumcreatinine,bilirubin,calcium,aspartateaminotransferase,albumin,alkalinephosphatase,andlactatedehydrogenase),uricacid,beta-2microglobulin,andvitaminDlevels.SerumproteinelectrophoresiswithIgG,IgA,andIgMimmunoglobulinlevelsarealsodone.Othertestsaredonedependingonfindings(eg,MRIofbrainand/orspinalcordforneurologicsymptoms).Ifuricacidlevelsarehigh,serumglucose-6-phosphatedehydrogenase(G6PD)levelischeckedbecauseG6PDdeficiencyGlucose-6-PhosphateDehydrogenase(G6PD)DeficiencyGlucose-6-phosphatedehydrogenase(G6PD)deficiencyisanX-linkedenzymaticdefectcommoninpeoplewithAfricanancestrythatcanresultinhemolysisafteracuteillnessesorintakeofoxidant...readmoreprecludestreatmentwithrasburicase,whichisoftengiventopreventtumorlysissyndromeTumorLysisandCytokineReleaseSyndromesAdverseeffectsarecommoninpatientsreceivinganycancertherapy,particularlycytopenias,gastrointestinaleffects,andtumorlysisandcytokinereleasesyndromes.Patientsmayalsohave...readmorebutmaycausehemolyticanemiainpatientswithG6PDdeficiency.TestingforetiologyPatientswithnon-HodgkinlymphomaareinitiallyscreenedforHIVHumanImmunodeficiencyVirus(HIV)InfectionHumanimmunodeficiencyvirus(HIV)infectionresultsfrom1of2similarretroviruses(HIV-1andHIV-2)thatdestroyCD4+lymphocytesandimpaircell-mediatedimmunity,increasingriskofcertain...readmoreandhepatitisBandCvirusesCausesofHepatitisHepatitisisinflammationofthelivercharacterizedbydiffuseorpatchynecrosis.Hepatitismaybeacuteorchronic(usuallydefinedaslasting>6months).Mostcasesofacuteviralhepatitis...readmore.PatientsdiagnosedwithadultT-cellleukemia/lymphoma(ATLL)arealsocheckedforhumanT-celllymphotropicvirustype1(HTLV-1HTLVInfections).StagingAfterdiagnosis,stageisdeterminedtoguidetherapy.ThecommonlyusedLuganostagingsystem(seetableLuganoStagingofHodgkinLymphomaandNon-HodgkinLymphomaLuganoStagingofHodgkinLymphomaandNon-HodgkinLymphoma)incorporatesSymptomsPhysicalexaminationfindingsResultsofimagingtests,includingCTofthechest,abdomen,andpelvis,andfunctionalimagingwithFDG-PETBonemarrowbiopsy(inselectedcases)AlthoughstageInon-Hodgkinlymphomadoesoccur,thediseaseistypicallydisseminatedwhenfirstrecognized.TableDiagnosisreference1.ChesonBD,FisherRI,BarringtonSF,etal:Recommendationsforinitialevaluation,staging,andresponseassessmentofHodgkinandnon-Hodgkinlymphoma:TheLuganoclassification.JClinOncol32(27):3059-3068,2014.PrognosisforNon-HodgkinLymphomasPrognosisvariesbythetypeandstageoflymphomaandindividualpatientfactors.Ingeneral,patientswithperipheralT-cellornaturalkiller(NK)/T-celllymphomastypicallyhaveaworseprognosisthanthosewithB-cellnon-Hodgkinlymphoma.Withineachnon-Hodgkinlymphomavariant,prognosisisrelatedtodifferencesintumorcellbiology.ThemostcommonlyusedprognosticscoringsystemistheInternationalPrognosticIndex(IPI)fordiffuselargeB-celllymphoma).However,theIPIscoreisusedonlyfordiffuselargeB-celllymphoma(DLBCL).Therearealsoscoringsystemsforfollicularlymphoma(FLIPI)andmantlecelllymphoma(MIPI).Onlinecalculatorsareavailabletoestimateprognosisinothertypesofnon-Hodgkinlymphomaaswell.TheIPIconsiders5riskfactors:Age>60yearsPoorperformancestatus(canbemeasuredusingtheEasternCooperativeOncologyGrouptool)Elevatedlactatedehydrogenase(LDH)level>1extranodalsiteStageIIIorIVdiseaseOutcomeisworsewithanincreasingnumberofriskfactors.Patientsinthehighestriskgroups(patientswith4or5riskfactors)havea50%5-yearsurvival.Patientswithoutanyoftheriskfactorshaveaveryhighcurerate.TheoriginalIPIscoreusesthe5factorsasdiscretevariables(eg,eitherageover60orunder60).Amodification,theDiffuseLargeB-cellLymphomaPrognosis(IPI24),whichcalculatesthechanceofbeingdiseasefreeat24monthsfromdiagnosis,includestheabovefactorsascontinuousvariablesandalsoincludesabsolutelymphocytecount.TreatmentofNon-HodgkinLymphomasWatchandwait(forindolent,largelyasymptomaticlymphomas)ChemotherapyRadiationtherapy(mostcommoninpatientswithlimited-stagediseaseandsometimesinthosewithadvanced-stagedisease)Immunotherapy(eg,monoclonalantibodiestargetingCD20,CD19,orCD79,orchimericantigenreceptorTcells[CARTcells])Targeteddrugs(eg,BTK[Brutontyrosinekinase]inhibitors,PI3K[phosphoinositide3-kinase]inhibitors,cerebloninhibitors)SometimeshematopoieticstemcelltransplantationHematopoieticStemCellTransplantationHematopoieticstemcell(HSC)transplantationisarapidlyevolvingtechniquethatoffersapotentialcureforhematologiccancers(leukemias,lymphomas,myeloma)andotherhematologicdisorders...readmore(autologousorallogeneic)Treatmentvariesconsiderablywithcelltype,whicharetoonumeroustopermitdetaileddiscussion.Generalizationscanbemaderegardinglimitedvsadvanceddiseaseandaggressivevsindolentforms.BurkittlymphomaBurkittLymphomaBurkittlymphomaisanaggressiveB-cellnon-Hodgkinlymphomaoccurringinchildrenandadults.Endemic(African),sporadic(non-African),andimmunodeficiency-relatedformsexist.(Seealso...readmoreandcutaneousT-celllymphomasCutaneousT-cellLymphomas(CTCL)MycosisfungoidesandSézarysyndromeareuncommonchronicT-cellnon-Hodgkinlymphomasprimarilyaffectingtheskinandoccasionallythelymphnodes.(SeealsoOverviewofLymphomaandNon-Hodgkin...readmorearediscussedseparately.Forpatientswithindolentlymphomasandnosignificantsignsorsymptomsoflymphoma,a"watchandwait"approach(withholdingtreatmentwhilecloselymonitoring)canbeused.Limiteddisease(stagesI-II)ForstageIindolentnon-Hodgkinlymphoma(uncommonbecausemostpatientshavestageIIoIVwhendiagnosed),externalbeamradiationtherapycanbethesoleinitialtreatment.Regionalradiationtherapymayofferlong-termcontrolandpossiblycureinabout40%ofstageIpatients.StageIIindolentnon-Hodgkinlymphomaismostcommonlytreatedasadvanced-stagedisease.Limited-stageaggressivenon-Hodgkinlymphomascanbemanagedwithacombinationofchemotherapyplusradiationtherapyorwithchemotherapyalone(plusanti-CD20monoclonalantibodiesforB-celllymphomas).PatientswithstageIBurkittlymphomaBurkittLymphomaBurkittlymphomaisanaggressiveB-cellnon-Hodgkinlymphomaoccurringinchildrenandadults.Endemic(African),sporadic(non-African),andimmunodeficiency-relatedformsexist.(Seealso...readmorearetreatedwithintensivecombinationchemotherapywithmeningealprophylaxis.Advanceddisease(stagesII-IV)StageIInon-Hodgkinlymphomaismanagedasadvancedstagediseaseinmanycircumstances.Mostpatientswithalltypesofnon-HodgkinlymphomawhohavestageIItoIVdiseasearecandidatesforchemoimmunotherapy.Inthesecases,radiationtherapymaybeusedtolimitthenumberofcyclesofchemoimmunotherapyorprovidelocalizedtreatmentforresidualsitesofbulkdisease.Forindolentlymphomas,treatmentvariesconsiderably.Becausetheselymphomasarehighlytreatablebutnotreliablycurable,treatmentmaynotberecommendedinitiallyforasymptomaticpatients,althoughsomepatientsaregivenanti-CD20immunotherapyusingrituximabalone.Thisstrategycandelaytheneedformyelosuppressivechemotherapy,butearlyimmunotherapyalonehasnotbeenshowntoimpactoverallsurvival.Patientswithsymptomsorbulkydiseasethatputsvitalorgansatriskaretreatedwithchemoimmunotherapy.Inselectedcases(eg,chemo-refractorywithlimitedbonemarrowinvolvement),radiolabeledanti-CD20antibodycanbeusedtotargetradiationtothetumorcellwithpotentiallyfewereffectsonnearbynormalorgans.InpatientswithaggressiveB-celllymphomas(eg,diffuselargeBcell),thestandarddrugcombinationisrituximabpluscyclophosphamide,hydroxydaunorubicin(doxorubicin),vincristine,andprednisone(R-CHOP).Acompleteresponsewithdiseaseregressionisexpectedin80%ofcases,withanoverallcurerateofabout60%.TheseresultsvarysignificantlybyIPIscore.Patientswhoarediseasefreeat≥24monthsfromdiagnosishavealifeexpectancysimilartothatoftheage-andsex-matchedpopulation.Thiskeyfactorcanguidefollow-upstrategiesinthispatientpopulation.PatientswithlowerIPIscoresmaybenefitfromaddingtheantibody-drugconjugatepolatuzumabvedotin,aCD79b-directedantibody-drugconjugatetoR-CHOP.TheapproachinperipheralT-cellnon-Hodgkinlymphomaandprimarycentralnervoussystemlymphomaisdifferent.Inthesepatients,autologousstemcelltransplantationHematopoieticStemCellTransplantationHematopoieticstemcell(HSC)transplantationisarapidlyevolvingtechniquethatoffersapotentialcureforhematologiccancers(leukemias,lymphomas,myeloma)andotherhematologicdisorders...readmoremaybeofferedtoinitialrespondersbeforerelapseoccurswiththeintentionofimprovingthelikelihoodofcure.Inautologousstemcelltransplantation,stemcellsareobtainedfromthepatientbyperipheralbloodleukopheresisandaretransfusedbackintothepatientafterhigh-dosechemotherapy.Similarly,insomeyoungerpatientswithmantlecelllymphomawhohaverespondedtoinitialtherapy,autologousstemcelltransplantationmaybeisdonetoprolongremission.LymphomarelapsePatientswithaggressivenon-Hodgkinlymphomanotinremissionatendoftherapyorwhorelapsearetreatedwithsecond-linechemotherapyregimensfollowedbyautologousstemcelltransplantationHematopoieticStemCellTransplantationHematopoieticstemcell(HSC)transplantationisarapidlyevolvingtechniquethatoffersapotentialcureforhematologiccancers(leukemias,lymphomas,myeloma)andotherhematologicdisorders...readmoreiftheyarerelativelyyoungandingoodhealth..Insomepatientsatveryhighriskofrelapseaswellasinthoseforwhomautologoustransplantisnotfeasibleorhasalreadyfailed,stemcellsfromamatchedsiblingorunrelateddonor(allogeneictransplants)canbeeffective.Ingeneral,theolderthepatient,thelesslikelyanallogeneictransplantationwillbeofferedbecauseolderpatientshavehigherratesoftransplantationcomplications.PatientswithdiffuselargeB-celllymphoma(DLBCL)whohavepersistentlymphomadespiteatleast2priorlinesoftherapymaybecandidatesforchimericantigenreceptor(CAR)Tcells.CARTcellsareTcells(mostcommonlyautologousTcells)thathavebeengeneticallyengineeredtorecognizeatumorantigen(eg,CD19).Afterinfusion,theyundergoactivationandexpansion.Aboutonethirdofpatientsachieveadurableresponsefromthistherapy.Patientsnoteligiblefortheabovetherapies,orforwhomtheyhavefailed,mayreceivetreatmentwithvarioustherapies,mostlyforpalliation.Thesetherapiesvarywidelyandareconstantlychangingasnewtreatmentsaredeveloped.Inindolentlymphomas,patientsmaybemanagedusingawidevarietyofstrategiesdependingonLymphoma-relatedfactors(eg,histopathology,stage,molecularandimmunologiccharacteristics)Patient-relatedfactors(eg,age,comorbidities)Thetypeofandresponsetopriortherapy.Manyofthesamedrugsusedforfirst-linetreatmentmaybegiventopatientsinrelapse.Insomecases,thesametreatmentmayberepeatedifitwaspreviouslyeffectiveandwelltolerated.High-dosechemotherapywithautologousstemcelltransplantationHematopoieticStemCellTransplantationHematopoieticstemcell(HSC)transplantationisarapidlyevolvingtechniquethatoffersapotentialcureforhematologiccancers(leukemias,lymphomas,myeloma)andotherhematologicdisorders...readmoreisusedoccasionallyinpatientswhohavehigh-risklymphomabiology(includingapoorresponsetochemotherapy),andalthoughcureremainsunlikely,remissionmaybesuperiortothatwithsecondarypalliativetherapyalone.Reducedintensityallogeneictransplantationisapotentiallycurativeoptioninsomepatientswithindolentlymphoma.Themortalityrateofpatientsundergoingmyeloablativetransplantationhasdecreaseddramaticallyto1to2%formostautologousproceduresandto15to20%formostallogeneicprocedures(dependingonage).ComplicationsoftreatmentAnimmediatecomplicationofmosttherapiesisinfectionthatoccursduringperiodsofneutropeniaNeutropeniaNeutropeniaisareductioninthebloodneutrophilcount.Ifitissevere,theriskandseverityofbacterialandfungalinfectionsincrease.Focalsymptomsofinfectionmaybemuted,butfever...readmore.Althoughuseofgrowthfactorsthatstimulatewhitebloodcellproductionhashelped,infectioncontinuestoposeaproblem.Thegastrointestinaladverseeffectsofchemotherapycanbelargelyrelievedorpreventedbyantiemeticsandbowelprograms.PatientsreceivinganthracyclinesareatriskofcardiomyopathyOverviewofCardiomyopathiesAcardiomyopathyisaprimarydisorderoftheheartmuscle.Itisdistinctfromstructuralcardiacdisorderssuchascoronaryarterydisease,valvulardisorders,andcongenitalheartdisorders...readmoreand/orarrhythmiasOverviewofArrhythmiasThenormalheartbeatsinaregular,coordinatedwaybecauseelectricalimpulsesgeneratedandspreadbymyocyteswithuniqueelectricalpropertiestriggerasequenceoforganizedmyocardial...readmore.Aftersuccessfultreatment,patientsshouldbereferredtoacancersurvivorshipclinicforacareplanthatcanbeimplementedbythepatient'sprimarycareteam.Thisplanistailoredtothepatient'scomorbiditiesandrisksspecifictothetreatmenttheyreceived.Drugsandradiationtherapyhavelatecomplications.Inthefirst10yearsaftertreatment,thereisariskofmyelodysplasiaMyelodysplasiaandIron-TransportDeficiencyAnemiaInmyelodysplasticsyndrome,anemiaiscommonlyprominent.Theanemiaisusuallynormocyticormacrocytic,andadimorphic(largeandsmall)populationofcirculatingcellscanbepresent....readmoreoracuteleukemiaAcuteleukemiasLeukemiaisamalignantconditioninvolvingtheexcessproductionofimmatureorabnormalleukocytes,whicheventuallysuppressestheproductionofnormalbloodcellsandresultsinsymptoms...readmoreduetobonemarrowdamagefromcertainchemotherapyagents.After10years,theriskofsecondarycancersincreases,especiallyinpatientswhoreceivedradiationtothechest.KeyPointsNon-Hodgkinlymphomasareagroupofrelatedcancersinvolvinglymphocytes;theyvarysignificantlyintheirrateofgrowthandresponsetotreatment.Thediseaseisusuallyalreadydisseminatedatthetimeofdiagnosis.Molecularandgenetictestsareessentialfordiagnosisandmanagement.Limitedindolentdiseasemaybetreatedwithradiationtherapy.Treatmoreadvanceddisease(indolentoraggressive)withimmunotherapy,chemotherapy,hematopoieticstemcelltransplantation,oracombinationdependingonthetypeandstageofnon-Hodgkinlymphoma.MoreInformationThefollowingisanEnglishlanguageresourcethatprovidesinformationforcliniciansandsupportandinformationforpatients.THEMANUALisnotresponsibleforthecontentofthisresource.Leukemia&LymphomaSociety:ResourcesforHealthcareProfessionals:provideseducationalresourcesforhealthcarepractitionersaswellasinformationforpatientreferrals ClickhereforPatientEducation NOTE: ThisistheProfessionalVersion. CONSUMERS: ClickherefortheConsumerVersion Copyright©2022Merck&Co.,Inc.,Rahway,NJ,USAanditsaffiliates.Allrightsreserved. HodgkinLymphoma WasThisPageHelpful? Yes No BurkittLymphoma Testyourknowledge TakeaQuiz!  BroughttoyoubyMerck&Co,Inc.,Rahway,NJ,USA(knownasMSDoutsidetheUSandCanada)— dedicatedtousingleading-edgesciencetosaveandimprovelivesaroundtheworld.LearnmoreabouttheMSDManualsandourcommitmenttoGlobalMedicalKnowledge. About Disclaimer Permissions Privacy CookieSettings Termsofuse Licensing ContactUs VeterinaryManual ThissitecomplieswiththeHONcodestandardfortrustworthyhealthinformation:verifyhere. Copyright©2022Merck&Co.,Inc.,Rahway,NJ,USAanditsaffiliates.Allrightsreserved. TOP