Rev. Bras. Hematol. Hemoter. vol.37 número5

rev bras hematol hemoter. 2015;37(5):285–286

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Revista

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Brazilian

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Scientific

Comment

Monoclonal

B-cell

lymphocytosis

夽

Irene

Biasoli

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_Nelson

_Spector

UniversidadeFederaldoRiodeJaneiro(UFRJ),RiodeJaneiro,RJ,Brazil

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Articlehistory:

Received9June2015 Accepted28July2015 Availableonline8August2015

ChronicB-celllymphocyticleukemia(B-CLL)represents0.9% ofallnewcancers.Itisestimatedthattherewillbealmost 15000newcasesand4600deathsduetoCLLin2015inthe USA.1_{Themedianagesatdiagnosisanddeathare71yearsand} 80years,respectively.1_{Thecriteriathatdefinethediagnosisof} B-CLLincludethepresenceofatleast5×106Blymphocytes/L

withthepeculiarCLLphenotype,persistingintheperipheral bloodforatleast3months.2

MonoclonalB-celllymphocytosis(MBL)ischaracterizedby an expansionof circulating clonal B lymphocytes, totaling lessthan 5×109/Linindividuals withoutanysymptomsor

signsofalymphoproliferativedisease.3,4_{Threecategoriesof} MBLhavebeenrecognized:CLL-likeMBL,atypicalCLL-MBL, andCD5-negativeMBL.Seventy-fivepercentofallcasesare CLL-likeMBL,andpresentthesamephenotypeasCLL(CD5, CD19,CD23andCD20dim_{,withlowsurfaceimmunoglobulin}

expression).3,4 _{Moreover,the clonalBcells inCLL-likeMBL} sharesimilarchromosomalabnormalitieswithB-CLL.

ArecentsystematicreviewreportedfrequenciesofMBL rangingfrom<1%to18.2%.5_{Thiswidevariationreflects} dif-ferent study populations (general population, blood donor population, outpatients from clinics and relatives of CLL patients–familialcasesorsporadiccases)andthesensitivity ofthemultiparameterflowcytometryemployed(twoorthree

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2015.05.006. 夽

SeepaperbyMatosetal.onpages292-5.

∗ _{Correspondingauthorat:FaculdadedeMedicina,UniversidadeFederaldoRiodeJaneiro(UFRJ),RuaProfessorPauloRocco,255,4.andar,} sala4A12,IlhadoFundão,RiodeJaneiro,RJ,Brazil.

E-mailaddress:irene.biasoli@gmail.com(I.Biasoli).

color antibody-fluorochrome combinations or four toeight color antibody-fluorochromecombinations). Furthermore,it iswellestablishedthattheprevalenceincreaseswithage.Ina recentstudyinSpain,608healthyindividualswereevaluated withaneight-colorantibodypanel.Theoverallprevalenceof MBL was14%;it wasaround 5%inunder 60-year-old indi-viduals, 17.5% inindividuals between60 and 69 years old, andreached75%inages>89years.6_{HighfrequenciesofMBL} (12–18%)havebeenobservedamongfirst-degreerelativesof familial CLLpatients, definedasafamilywithatleasttwo first-degreerelativeswithCLL.However,long-termfollow-up studiesoftheMBLindividualsidentifiedamongrelativesof familialCLLpatientsarestilllacking.7,8

MBLcanbefurtherclassifiedas‘high-countMBL’or ‘low-countMBL’dependingonthenumberofcirculatingBcells(the sizeoftheclone).Oneacceptedcut-offtodistinguishbetween thesetwocategoriesis5×109/LclonalBcells.4,9 High-count

MBLisalsocalled‘clinicalMBL’becauseitisoftendetected duringaninvestigationoflymphocytosis.Themediannumber ofBcellsisaround3×109/L,and95%ofthecasespresentmore

than4.5×109lymphocytes/L.TheriskofprogressiontoCLLis

around1%peryear.10_{Incontrast,inlow-countMBLalmost} 95%ofthecaseshavelessthan1.0×109/LclonalBcellsand

havealowriskofprogressiontoCLL.11_{Ofnote,thiscondition}

http://dx.doi.org/10.1016/j.bjhh.2015.06.003

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israrelyfoundintheclinicalpractice,sincehigh-sensitivity techniquesarerequiredforitsdetection.9

Someauthorshavearguedthatlow-countMBLmightnot beanactualpre-leukemicstate,reflectinginstead immune senescenceorpersistentantigenstimulation.Onestudy,in particular,comparedtheimmunogeneticprofileoflow-count andhigh-countCLL-likeMBLwithearlystageCLL(Raistage0). Theyfoundthathigh-countMBLwassimilartoCLLRaistage 0,whilelow-countMBLwasnot.12

AlthoughvirtuallyallCLLcasesevolvefromCLL-likeMBL,13 noteveryindividualwithCLL-likeMBLhasthesameriskof progressiontoCLL.Sofar,thenumber ofclonalB lympho-cytesistheonlywell-establishedfactorcorrelated withthe likelihoodoftransformationtoCLL.9_{Twostudiesshowedthat} B-cellcountsatpresentationbelow1.2×109or1.9×109/L

pre-dictedastablecourse,whilecountsover3.7×109/Lpredicted

risinglymphocytenumbersovertime.14,15_{Furtherstudiesare} neededtodetermineotherbiologicalfactorsassociatedwith ahigherriskofprogression.9

Intheirfirstreportin2009,whilestudying167first-degree relativesofsporadic(non-familial)CLLpatients,Matosetal. reportedanoverallprevalenceof4.1%,reaching15.6%inover 60-year-oldindividuals.16_{Theauthorssuggestedthat,asthe} prevalenceinolderrelativesofsporadicCLLpatientswas sim-ilartothatreportedamongrelativesoffamilialCLLpatients, theriskofMBLmightbesimilarandalsosusceptibilityforthe developmentofCLL.Inthepresentstudy,theauthors have analyzedthelong-termoutcomeoffiveoutoftheseven indi-vidualswithMBL.17 _{Allhadpresentedwithlow-countMBL.} Afteramedianfollow-upof7.6years,noprogressiontoCLL was observed, and the size ofthe clones remained stable. TheseresultsareinlinewithpreviousstudiesinCLL-likeMBL detectedinthegeneralpopulation.

Inconclusion,currentevidencedoesnotsupport system-atic laboratorymonitoringoflow-countMBL individuals to detectprogression;clinicalandlaboratorymonitoringisonly recommendedinhigh-countMBL.Alsoforthelattergroup, openquestionsremainregardingbiologicalfactorsthatcould predictthe risk ofprogression, and whetherits distinction from CLL Rai stage 0 based on the arbitrary threshold of 5×109/Lhasanybiologicalorclinicalsignificance.

Conflicts

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interest

Theauthorsdeclarenoconflictsofinterest.

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