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w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Original

article

Mature

B

cell

neoplasms:

retrospective

analysis

of

93

cases

diagnosed

between

2011

and

2014

in

a

University

Hospital

in

southern

Brazil

Chandra

Chiappin

Cardoso,

Ana

Carolina

Rabello

de

Moraes,

Joanita

Angela

Gonzaga

Del

Moral,

Maria

Claudia

Santos-Silva

UniversidadeFederaldeSantaCatarina(UFSC),Florianópolis,SC,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received12November2015 Accepted7February2016 Availableonline9March2016

Keywords:

MatureB-cellneoplasms Diagnosis

Prognosis

Treatmentresponse

a

b

s

t

r

a

c

t

Background:Accordingtothe2008WorldHealthOrganizationclassification,matureB-cell neoplasmsareaheterogeneousgroupofdiseasesthatincludeB-celllymphomasandplasma cell disorders.Theseneoplasmscanhaveverydifferentclinicalbehaviors,fromhighly aggressivetoindolent,andthereforerequirediversetreatmentstrategies.

Objective:Theaim ofthisstudywastoassesstheprofileof93patientsdiagnosedwith matureB-cellneoplasmsmonitoredbetween2011and2014.

Methods:Areviewofpatients’chartswasperformedandlaboratoryresultswereobtained usingtheonlinesystemoftheUniversidadeFederaldeSantaCatarina.

Results:Thestudyincluded93adultpatientswithmatureB-cellneoplasms.Themost fre-quentsubtypesweremultiplemyeloma,chroniclymphocyticleukemia,diffuselargeB-cell lymphoma,follicularlymphoma,andBurkitt’slymphoma.Themedianageatdiagnosiswas 58yearswithamale-to-femaleratioof1.3:1.Therewerestatisticaldifferencesintermsof ageatdiagnosis,lactatedehydrogenaseactivityandKi-67expressionamongthesubtypes ofB-celllymphoma.Accordingtotheprognosticindexes,themajorityofmultiplemyeloma patientswerecategorizedashighrisk,whilethemajorityofchroniclymphocyticleukemia patientswereclassifiedaslowrisk.

Conclusions: ThisstudydemonstratestheprofileofpatientsdiagnosedwithmatureB-cell neoplasmsinasouthBrazilianuniversityhospital.OftheB-celllymphoma,Burkitt’s lym-phomapresentedparticularfeaturesregardinglactatedehydrogenaseactivitylevels,Ki-67 expression,ageatdiagnosis,andhumanimmunodeficiencyvirusinfection.

©2016Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.Allrightsreserved.

Correspondingauthorat:Divisãode AnálisesClínicas,HospitalUniversitário,UniversidadeFederaldeSanta Catarina(UFSC),Rua

ProfessoraMariaFloraPausewang,s/n◦,Trindade,88036-800Florianópolis,SC,Brazil.

E-mailaddress:maria.claudia.silva@ufsc.br(M.C.Santos-Silva).

http://dx.doi.org/10.1016/j.bjhh.2016.02.003

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Introduction

MatureB-cellneoplasms(MBCN)areaheterogeneousgroupof diseasesthatcomprisesB-celllymphomas(BCL)andplasma cellneoplasms(PCN).1AboutfifteensubtypesofBCLandfive

subtypes ofPCN are categorized in the 2008World Health Organization(WHO)TumorsofHematopoieticandLymphoid Tissues.1MBCNpresentvariableclinicalpresentationsfrom

highlyaggressivetoindolent,andthereforerequiredifferent treatmentstrategies.2

EpidemiologicaldataplaceMBCNasasubstantialglobal healthproblem.IntheWesternworldwithabout20newcases oflymphomabeingdiagnosedper100,000peopleannually,2

whichaccountsfor3–4%ofallmalignancies.3Moreover,

mul-tiplemyeloma(MM)accountsfor1%ofallmalignancies,with aglobalincidenceofnearly120,000casesperyear.4

Similartoothertypesofcancer,MBCNarisebymultistep accumulationofgeneticaberrationsthatinduceaselective growthadvantageofthemalignantclone.Commonly,the ini-tialstepsinthemalignanttransformationarechromosomal translocations,whichmightoccurduringdifferentstagesof B-celldifferentiation.5

Inadditiontothe recentadvancesintheunderstanding ofgenetic and genomic characteristics ofB-cell malignan-cies,remarkableefforthasbeenmadetounderstandpotential risk factors that accountfor the increase in the incidence of MBCN, particularly in relation to the environment and lifestyle.Severe immunosuppressionresulting from immu-nodeficiencysyndromesandafterorgantransplantation,and someinfectiousagentsareknownriskfactorsforthe devel-opment of some lymphoma subtypes.6 Much attention is

beingpaidtothehigh riskoflymphomainhuman immu-nodeficiency virus (HIV)-positive patients (60 to 200-fold).7

In addition, studies have suggested there is an increased riskoflymphomasand MMinrelationto theuse ofsome pesticides.8 Additionally,the contributionofenvironmental

factors,suchassmoking,andlifestyleincludingdietremain unclear.6

ConsideringthelackofBrazilianstudiesonthisissueand thelackofepidemiologicaldata,thepresentstudywas con-ductedtoprovide informationaboutthe profileofpatients whohavedevelopedthistypeofneoplasm.Thus,theaimof thisstudywastoassesstheprofileof93patientsdiagnosed withMBCNmonitoredbetween2011and2014inauniversity hospitalinsouthernBrazil.

Methods

Studyparticipants

ThesubjectscomprisedadultpatientsdiagnosedwithMBCN duringthe periodcoveredbythe study (June2011–October 2014) and monitoredatthe university hospitalofthe Uni-versidadeFederaldeSantaCatarina(UFSC),Florianópolis,SC, Brazil.Patientswereexcludediftheirrecordswere unavail-ableoriftheydidnotsigntheconsentform.Thisstudywas approvedbytheEthicsCommitteeoftheinstitution.The uni-versityhospitalofUFSCtreatsanaverageof250,000patients

peryear.Fromthistotal,anaverageof2400patientsperyear areattendedattheHematologyClinicandaround240patients peryeararehospitalizedbytheHematologyService.

Design

Clinical and personaldatawere obtainedthroughareview ofpatientchartsfrom thehospitalwiththe confidentiality ofinformationbeingpreserved.Laboratorytestresultswere obtainedthroughtheonlinehospitalsystem.Clinicaland lab-oratorydatawererecordedonadatacollectionformandlater compiledforstatisticalanalysis.

Collected dataincludedvariablessuchasageat diagno-sis,yearofdiagnosis,gender,race/ethnicity,literacy,serology, clinical manifestationsatdiagnosis,co-morbidities, labora-toryexamsatdiagnosis,neoplasmstageorstratification,and outcome.Outcome wasclassified asoneoftwocategories: complete/partialremission(CR/PR)andrelapsed/progressive disease (PD) basedon previous establishedcriteria.9,10 The

endofthedatacollectionperiodwasestablishedasFebruary 2015.

Statisticalanalysis

Databasepreparationandstatisticalanalysiswereperformed usingtheStatisticalPackageforSocialSciences(SPSS®version

17.0)andMedCalc® (version12.3.0.0).Dataarepresentedas

descriptivestatisticsincludingabsoluteandrelative frequen-ciesforcategoricalvariablesandmeasuresofcentraltendency anddispersionofcontinuousvariables.Continuousvariables were tested for normality using the Kolmogorov–Smirnov andShapiro–Wilktests.Numericalvariableswerecompared betweengroupsusingtheMann–WhitneyUtestorStudent’s

t-test.Acomparisonofthreeormorevariableswasperformed employing the Kruskal–Wallis test or one-way analysis of variance (ANOVA). Thefrequencies obtained incategorical variableswerecomparedbetweenpatientsbythechi-square orFisher’sexacttest.Asignificancelevelof5%(p-value<0.05) wasconsideredsignificant.

Results

MatureBcellneoplasms

Atotalof93patientswerediagnosedwithasubtypeofMBCN, includingBCLandPCN,from2011to2014.Themedianage atdiagnosiswas58years(range:20–93years)witha male-to-femaleratioof1.3:1.Patientgeneralcharacteristicsarelisted inTable1andprevalenceofthedifferentsubtypesofMBCN casesareshowninFigure1.Thecorrespondingage distribu-tionsareshowninFigure2.

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Multiple myeloma

CLL/SLL

DLBCL

Follicular lymphoma

Burkitt lymphoma

BCL-U

MGUS

Hairy cell leukemia

Marginal zone lymphoma

BCL-NOS

Mantle cell lymphoma 15.1%

12.9% 11.8%

7.5% 6.5% 4.3% 4.3%

3.2% 3.2%

2.2%2.2%2.2%

1.1%

23.7%

LPL/WM

Plasmablastic lymphoma

Plasma cell leukemia

Figure1–PrevalenceofthematureB-cellneoplasmssubgroups.

CLL/SLL:chroniclymphocyticleukemia/smalllymphocyticlymphoma;DLBCL:diffuselargeB-celllymphoma;BCL-U:B-cell lymphoma,unclassifiable,withfeaturesintermediatebetweenDLBCLandBurkitt’slymphoma;MGUS:monoclonal gammopathyofundeterminedsignificance;BCL-NOS:B-celllymphoma,nototherwisespecified;LPL/WM:

lymphoplasmacyticlymphoma/Waldenströmmacroglobulinemia.

Plasmablastic lymphoma Plasma cell leukemia LPL/WM BCL-U BCL-NOS Hairy cell leukemia

Multiple myeloma Marginal zone lymphoma Mantle cell lymphoma Burkitt lymphoma DLBCL Follicular lymphoma CLL/SLL

20 18 63

19

44 59

Min Median Max

1st quartile 3rd quartile 100

Age at diagnosis

MBCN subtype

MGUS

Figure2–AgeatdiagnosisofmatureB-cellneoplasms.

CLL/SLL:chroniclymphocyticleukemia/smalllymphocyticlymphoma;DLBCL:diffuselargeB-celllymphoma;BCL-U:B-cell lymphoma,unclassifiable,withfeaturesintermediatebetweenDLBCLandBurkitt’slymphoma;MGUS:monoclonal gammopathyofundeterminedsignificance;BCL-NOS:B-celllymphoma,nototherwisespecified;LPL/WM:

lymphoplasmacyticlymphoma/Waldenströmmacroglobulinemia.

B-celllymphoma

Overall,66patients werediagnosedwithasubtypeofBCL. Therewerestatisticaldifferencesintermsofageatdiagnosis betweenBLandchroniclymphocyticleukemia/small lympho-cyticlymphoma(CLL/SLL –p-value=0.001),BL andBCL not otherwisespecified(BCL-NOS–p-value=0.041),and BLand mantlecell lymphoma(MCL – p-value=0.016). In addition,

intermsofserum lactatedehydrogenase(LDH)astatistical difference(p-value=0.003)wasfoundbetweenthedifferent groups(Table2).

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Table1–Patientgeneralcharacteristics(n=93).

Characteristic n %

Gender

Male 53 57.0

Female 40 43.0

Race

White 85 91.4

Otherunspecified 4 4.3

Unknown 4 4.3

Literacy

Incompleteelementaryschool 40 43.0

Completeelementaryschool 13 14.0

Completehighschool 30 32.3

Completehighereducation 9 9.7

Unknown 1 1.1

HIV

Positive 9 9.7

Negative 65 69.9

Unknown 19 20.4

HBV

Positive 5 5.4

Negative 66 71.0

Unknown 22 23.7

HCV

Positive 2 2.2

Negative 69 74.2

Unknown 22 23.7

Smoker

Non-smoker 3 3.2

Ex-smoker 11 11.8

Smoker 12 12.9

Passivesmoker 1 1.1

Unknown 66 71.0

Exposuretopesticides

Absent 86 82.5

Present 7 7.5

Previousneoplasia

Absent 87 93.5

Present 6 6.5

Diabetes

Absent 77 82.8

Present 16 17.2

Hypertension

Absent 49 52.7

Present 44 47.3

HIVpositive (n=9)

Burkitt’slymphoma(n=4) Multiplemyeloma(n=1) BCL-U(n=2)

Plasmablasticlymphoma(n=2) HBVpositive

(n=5)

Follicularlymphoma(n=1) DLBCL(n=1)

Burkitt’slymphoma(n=1) Hairycellleukemia(n=1) BCL-U(n=1)

HCVpositive (n=2)

DLBCL(n=1) BCL-U(n=1)

MBCN:mature B-cellneoplasm; HIV:human immunodeficiency virus;HBV:hepatitisBvirus;HCV:hepatitisCvirus;DLBCL:diffuse largeB-celllymphoma;BCL-U:B-celllymphoma,unclassifiablewith featuresintermediatebetweenDLBCLandBurkitt’slymphoma.

Table2–Serumlactatedehydrogenaseactivityin

patientsdiagnosedwithB-celllymphoma(n=66).

BCLsubtype LDH(IU/L)

Median(range)

CLL/SLL 188(116–332)a

DiffuselargeB-celllymphoma 406(184–2739)b

Follicularlymphoma 229(150–315)a

Burkitt’slymphoma 1534(243–7239)b

BCL-U 464(170–6121)b

Hairycellleukemia 152(141–402)a

Marginalzonelymphoma 137(113–397)a

BCL-NOS 215(182–232)a

Mantlecelllymphoma 222

LPL/WM 214(128–300)a

Plasmablasticlymphoma 174(148–199)a

LDH: lactate dehydrogenase; CLL/SLL: chronic lymphocytic leukemia/small lymphocytic lymphoma;BCL-U: BCL, unclassifi-able,withfeaturesintermediatebetweenDLBCLandBL;BCL-NOS: BCL not otherwisespecified; LPL/WM: lymphoplasmacytic lym-phoma/Waldenströmmacroglobulinemia.

There was a significant difference between ‘a’ and ‘b’ by the Kruskal–WallisandMann–WhitneyUtests.

infiltration.Inaddition,12patientswereevaluatedregarding central nervous system (CNS) involvement. Three patients withBLandtwowithBCL-UhadCNSinfiltration.

Ki-67 expression was evaluated by immunohistochem-istry(IHC)in30patients.SimilartoLDHlevels,astatistical difference was foundbetween groups (p-value=0.013).The subtypes with the highest Ki-67 expressions were DLBCL, BL,andBCL-UwithmedianKi-67expressionof80%(range: 50–95%), 92.5% (range: 50–95%), and 80% (range: 30–95%), respectively.ThemedianexpressionofKi-67fortheCLL/SLL group was 30% (range: 10–50%) and for the follicular lym-phomagroupitwas35%(range:10–50%).

MostcommonmatureBcellneoplasms

Themostcommonsubtypes ofMBCNfoundinthepresent studyinvolved66patients:MM(n=22),CLL/SLL(n=14),DLBCL (n=12),FL(n=11)andBL(n=7).Figure3showsstratificationof patientsbyMBCNsubtype.Responsetotreatmentwas evalu-atedasCR/PRandPD(Figure4).CLL/SLLpresentedthehighest frequencyofCR/PR(87.5%),whileBLpresentedthehighest frequencyofPD(83.3%).

Discussion

Thepresent studyretrospectivelyanalyzedtheclinical and laboratorialdataof93MBCNpatientsinaBrazilian univer-sityhospital.ThefrequenciesoftheMBCNsubtypesfoundin thisstudyaresimilartothosedescribedininternationaland Brazilianstudies.11,12

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A

B

C

n=3

13.6% n=2

14.3%

n=1 7.1%

n=1 7.1%

n=5 35.7%

0A

IA

IIA

IIIC

IVB

IVC

n=4 28.6% n=1

7.1% n=3

13.6%

n=4 18.2%

n=12 54.6%

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0.0

DLBCL 25.0 33.3 16.7 25.0

45.5

54.5

14.3 71.4 14.3

FL BL

High risk

High-intermediate risk

Intermediate risk

Low risk ISS I

ISS II

ISS III

ND

Figure3–Stratificationofpatientswith(A)multiplemyeloma,(B)chroniclymphocyticleukemia/smalllymphocytic lymphoma,and(C)diffuselargeB-celllymphoma,follicularlymphomaandBurkitt’slymphoma.

DLBCL:diffuselargeB-celllymphoma;FL:follicularlymphoma;BL:Burkitt’slymphoma;ND:notdefinedbecauseofthe absenceoftheresultof␤2-microglobulin.

cases),CLL/SLL(835cases),FL(446cases),marginalzone lym-phoma(390cases),MCL(100cases),BL(54cases),andhairy cellleukemia(48cases).11Thedatathatdifferscomparedto

thepresentstudyisthefrequencyofBL,whichinthisreport wasthefifthmostcommonMBCNsubtype.

InBrazil, astudy published in 2011inthe State ofSão Pauloontheprevalenceofnon-Hodgkinlymphoma(NHL) sub-typesin546casesreportedthefollowingfrequencies:DLBCL in49.45%ofthecases,FLin7.69%,BLin6.41%,diffuseand smallcelllymphoma(unclassifiable)in6.41%,andCLL/SLLin 6.23%.12Thus,theprevalenceofBLintheStateofSãoPaulo

(SoutheasternregionofBrazil)issimilartothatfoundinthe presentstudy;however,theprevalenceofCLL/SLLis discord-ant.

Moreover,Queirogaetal.demonstratedthedistributionof BLinthefiveBrazilianregionsandanalyzedthecasesinterms ofage(pediatricoradult),amongotherparameters. Interest-ingly,BLinthesouthernregionmainlyaffectsadultpatients (67%),whileintheother fourregionsthemajorityofcases arepediatricpatients.13Thisdatacorroboratesthehigher

fre-quencyofBLinthepresentstudy,whichiscomposedentirely byadultpatientsfromsouthernBrazil.

Accordingtodata fromthe MinistryofHealth ofBrazil, thecity ofFlorianopolisisthirdintheranking ofBrazilian citiesintermsofHIVdetectionandmortalityrates;infact,the southleadstherankingofthehighestdetectionrates(∼2.3×

thecountryrate).14ThehighlocalprevalenceofHIVinfection

mayhaveledtothehighrateofBLinthepresentstudy,since thereisanincreasedriskofdevelopingBLinpatientswithHIV infection.15

ThefrequencyofpatientswithMBCNwhowere seropos-itive for HIV was 9.7%, which is higher than the results foundbyShielsetal.Theseauthorsassessed115,643North American NHL cases and observed a rate of 5.9% of HIV infection.16 MBCNsubtypesthat havebeen associatedwith

thisinfection includeDLBCL,BL,Hodgkin’slymphoma(HL), primaryeffusionlymphomaandplasmablasticlymphomaof theoralcavity.7Ofthesubjectsinthecurrentstudywhowere

seropositive forHIV, four had BL, twohad BCL-U and two hadplasmablasticlymphomaoftheoralcavity.Ontheother hand,PCNarenotcommonlyassociatedwithHIVinfection andtheseneoplasmsusuallyaffectolderindividuals.17

How-ever,therearereportsofMMdevelopinginyoungerpatients withHIV,afindingthatiscompatiblewithacaseofMMina 43-year-oldHIV-positivesubjectinthisseries.

Studieshavedemonstratedanassociationbetween smok-ingandthedevelopmentoflymphomas,specificallyFL.18,19

Ofthe12currentsmokersincludedinthisstudy,fourwere diagnosed with FL.In addition, four cases were diagnosed withCLL/SLL;however,noassociationbetweenCLL/SLLand smokingwasfoundintheliterature.

According to the 2008 data from the Ministry of Agri-culture,BrazilsurpassedtheUnitedStatesinpesticideuse, anditisnowtheworld’slargestmarket.Thisfacthighlights the importance ofstudies thatinvestigate the relationship between thesepotentialcarcinogens and thehealth ofthe populationexposedtothem.20 Inthisstudy,sevenpatients

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MM

DLBCL

BL n=6 35.3%

n=11 64.7%

n=1 12.5%

n=7 87.5%

n=3 42.9% n=6

50.0%

n=1 16.7%

Complete/partial remission

Relapsed/progressive disease n=5

83.3% n=6 50.0%

n=4 57.1% CLL/SLL

FL

Figure4–Treatmentresponseassessedascomplete/partial remissionandrelapsed/progressivedisease.

MM:multiplemyeloma;CLL/SLL:chroniclymphocytic leukemia/smalllymphocyticlymphoma;DLBCL:diffuse largeB-celllymphoma;FL:follicularlymphoma;BL: Burkitt’slymphoma.

thosefromapreviousstudy,whichfoundapositive associ-ationbetweenindividualsexposedtospecificpesticidesand thedevelopmentofMMandCLL/SLL.8

Inthis study,themedianage atdiagnosiswas 58years similar to another Brazilian study that reported a median age of 50 years for NHL patients.12 Conversely, a

world-wideepidemiologicalstudy showedthatthemedianageof patientsdiagnosedwithlymphomasisaround70years,with onlyafewsubtypes,suchasFL,BL andprimary mediasti-nallymphoma, affecting younger patients.3 Indeed, inthe

presentstudyBLpatientspresentedamedianageof33years which was statistically different to that ofother subtypes ofBCL.

MBCNmayhaveaclinicalcourserangingfromindolentto extremelyaggressive.2,21Thus,apartfromcorrectdiagnosis,

prognosticstratificationisfundamentaltodefinethemedical strategy,whichcanrangefromjustawatch-and-wait strat-egytocombinedchemotherapyregimens.22ConsideringBCL,

themostimportantlaboratoryteststoevaluatethedegreeof neoplasmaggressivenessareserumLDHenzymeactivityand thepercentageofKi-67proteinevaluatedusingIHC.Sincethe 1970s,highserumLDHactivityisconsideredanindependent poorprognosticfactor.23 Inthe present study,asignificant

differencebetweenBCLsubtypeswasobservedinrespectto thisparameter.ThehighestvalueswereobservedinBLwith amedianof1534IU/L(range:243–7239IU/L).Moreover,serum LDHactivitywasindividuallyanalyzedamongBLpatientsand showedthatinonlyonecasetheactivityofthisenzymeat diagnosiswaslessthan500IU/L(243IU/L).Interestingly,this wasalsotheonlypatientwhoachievedCR/PRwithtreatment, andisinagoodgeneralcondition.

Morerecently,theevaluationofKi-67expressionhasbeen consideredaprognosticfactorforlymphomas,sinceit indi-cates the cell proliferation rate.24 Thus, as found for LDH

activity,thehighestvaluesofKi-67expressionwereobserved incasesofBL,DLBCL,andBLC-U.Theseresultsaresimilarto thosereportedbyBroydeetal.,whoshowedtheexpression ofKi-67inDLBCL,FL,CLL/SLL,atypicalBL,andMCLas67.5%, 32.1%,10.8%,96.5%,and40.2%,respectively.24

Furthermore,themostcommonsubtypesofMCBNwere stratifiedaccordingtoprognosticindexesinordertoestablish thestageofthetumoratdiagnosis.OftheMMcases(n=22), 54.6%(n=12)werestratifiedasinternationalstagingsystem (ISS)III,i.e.,thehighestriskcategoryforthistypeofneoplasm. Ofthese12patients,fourdiedwithin,onaverage,11monthsof diagnosis.Adifferentprofilewasfoundwhenprognostic strat-ificationof756patientswasassessedinapreviousstudythat includeddatafrom 16BrazilianInstitutions withMMcases diagnosedbetween1998and2004.Theresultsshowedthat 20.1%ofpatientswerestratifiedasISSI,48.7%asISSII,and 31.2%asISSIII.25Ontheotherhand,aChinesestudy

evalu-ated264casesofMMclassifiedas8.7%ISSI,36.4%ISSII,and 54.9%ISSIII,26whichissimilartothefrequenciesfoundinthe

presentstudy.DiagnosisofMMinadvancedstagescouldbe relatedtolackofinformationandunspecificsymptomssuch asbone lesions,which leadpatientstoseek othermedical specialtiesandoftenresorttoself-medication.

Withadifferentprofile,64.3%(n=9)ofpatientsdiagnosed withCLL/SLL(n=14)werestratifiedinlowerriskstages includ-ing0andIoftheRaisystemandAoftheBinetsystem.This dataissimilartotheresultsofastudypublishedin2014that evaluated924casesofCLL/SLLandfoundthefollowing fre-quencies fortheRaisystem:58%wereclassifiedasstage0, 34% asI/II and 8%asIII/IV; and forthe Binetsystem: 93% wereclassifiedasA/B,and7%asC.Accordingtothe litera-ture,stages0andAarerelatedtoahigheroverallsurvival (OS),withanexpectedmedianofabouttenyears.RaistagesI andIIandBinetstageBhaveintermediatemedianOSoffive tosevenyears,whilethemostaggressivegroups(RaiIIIand IVandBinetC)haveamuchshortermedianOSoflessthan threeyears.27

Limitationsofthisstudyincludethesmallpatientsample sizeandtheshortfollow-upperiod.Thelackofinformationon HIV,HBVandHCVstatusisanotherpotentialsourceofbias.

Conclusion

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Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgement

TheauthorsthanktheCentroNacionaldeDesenvolvimento CientíficoeTecnológico(CNPq)forfinancialsupport.

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Imagem

Figure 1 – Prevalence of the mature B-cell neoplasms subgroups.
Table 2 – Serum lactate dehydrogenase activity in patients diagnosed with B-cell lymphoma (n = 66).
Figure 3 – Stratification of patients with (A) multiple myeloma, (B) chronic lymphocytic leukemia/small lymphocytic lymphoma, and (C) diffuse large B-cell lymphoma, follicular lymphoma and Burkitt’s lymphoma.
Figure 4 – Treatment response assessed as complete/partial remission and relapsed/progressive disease.

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