w w w . r b h h . o r g
Revista
Brasileira
de
Hematologia
e
Hemoterapia
Brazilian
Journal
of
Hematology
and
Hemotherapy
Original
article
Adult
T-cell
leukemia/lymphoma
treatment
in
Bahia,
Brazil
Pedro
Dantas
Oliveira
a,∗,
Ítala
Gomes
a,
Victor
Hugo
Gomes
Souza
b,
Ernesto
Cunha
Pires
c,
Glória
Bomfim
Arruda
a,
Achiléa
Bittencourt
aaUniversidadeFederaldaBahia(UFBA),Salvador,BA,Brazil
bAssistênciaMultidisciplinaremOncologia(AMO),Salvador,BA,Brazil
cInstitutodeHematologiaeHemoterapiadeFeiradeSantana(IHEF),FeiradeSantana,BA,Brazil
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Articlehistory:
Received20February2016 Accepted21September2016 Availableonline22October2016
Keywords:
AdultT-cellleukemia/lymphoma ATL
PeripheralT-cell leukemia/lymphoma
HumanT-celllymphotropicvirus type-1
HTLV-1infection
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Background:AdultT-cellleukemia/lymphomaisaperipheraldiseaseassociatedwithhuman T-celllymphotropicvirustype1.Treatmentiscarriedoutaccordingtoclinicaltypewith watchful waiting being recommendedforlessaggressivetypes. AggressiveadultT-cell leukemia/lymphomaisgenerallytreatedwithchemotherapyand/orantivirals.The objec-tiveofthisstudywastocorrelatethesurvivalofpatientsdiagnosedinBahia,Brazil,with thetherapeuticapproachesemployedandtoevaluatewhatissuesexistedintheirtreatment processes.
Methods:Eighty-threeadultT-cellleukemia/lymphomapatients(26smoldering,23chronic, 16 acute, 13 lymphomaand fiveprimarycutaneous tumoral)with availabledata were includedinthisstudy.
Results:Completeresponsewasachievedinsevensmolderingpatientswithsymptomatic treatment,intwowithchronicdiseaseusingantivirals/chemotherapy,inonewithacute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide,doxorubicin,andprednisolone(VCAP);doxorubicin,ranimustine,and prednisolone(AMP);andvindesine,etoposide,carboplatin,andprednisolone(VECP)]. Smol-deringpatientswhoreceivedsymptomatictreatmentpresentedlongersurvival.Favorable chronicpatientstreatedwithantiviralspresentedlongersurvivalcomparedtothe unfa-vorablesubtype.However,fortheacuteform,first-linechemotherapywasbetter,albeit withoutsignificance,thanantivirals.Onlyoneofthepatientswithlymphomaandprimary cutaneoustumorsresponded.
Conclusions: Watchfulwaitingassociatedwithphototherapyrepresentsthebestoptionfor smolderingadultT-cellleukemia/lymphomawithsurvivalinBahiabeingsuperiortothat describedinJapan.Therewasatrendofbetterresultswithzidovudine/interferon-alphain
∗ Correspondingauthorat:Servic¸odeDermatologiadoComplexoHUPES,AmbulatórioMagalhãesNeto,3◦andar,RuaPadreFeijó,240,
Canela,40110-170Salvador,BA,Brazil.
E-mailaddress:pedrodermato@yahoo.com.br(P.D.Oliveira). http://dx.doi.org/10.1016/j.bjhh.2016.09.012
favorablechronicdisease.Excellentresultswereachievedinthelymphomatypetreated withtheLSG15protocol.Patientsarediagnosedlateprobablyduetolackofknowledgeof adultT-cellleukemia/lymphomabyprimaryhealthcaredoctorsandaBraziliantreatment protocolneedstobeestablished.
©2016Associac¸ ˜aoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
HumanT-celllymphotropicvirustype1(HTLV-1)isendemic insouthwesternJapan, sub-Saharan Africa,SouthAmerica andtheCaribbeanwithfociintheMiddleEastand Australo-Melanesia.1Aseroprevalencestudyinthegeneralpopulation ofSalvador,Bahia, Brazilshowed a rate of1.7%of HTLV-1 infectedindividuals.2
AlthoughthemajorityofHTLV-1carriersremain asymp-tomatic, around 10% develop serious diseases such as adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy/tropicalspasticparaparesis(HAM/TSP), HTLV-1-associateduveitis and infectivedermatitis associated with HTLV-1(IDH).3 ATLisanaggressivelymphoproliferative dis-easeofperipheralTcellscharacterizedbyshortsurvivaland apoorresponsetochemotherapy.4
Diagnostic criteria for ATL include positive serology for HTLV-1and ahistologically or cytologically proven periph-eralT-cellmalignancy.Wheneverpossible,theHTLV-1proviral integrationanalysisshouldbeperformed,exceptinclinically andmorphologicallystraightforwardcaseswhenitisunlikely that confirmation of HTLV-1 viral integration is necessary for diagnosis.5,6 In endemic areas, it is rare that HTLV-1-associatedlymphomasdonotexistinseropositivepatients.5
Due to diverse presentations, ATL is classified into five clinicaltypes:smoldering,chronic,acute,primarycutaneous tumoral(PCT)andlymphoma(Table1).4,7
ThemostaggressiveformsofATLaretheacute,lymphoma, PCTandunfavorablechronicforms.Smolderingandthe favor-ablechronicformsofATLarelessaggressive.5
Difficulty in the treatment of ATL is essentially due tochemotherapyresistanceand theimmunedysregulation causedbyHTLV-1infectionmakingthepatientsmore suscep-tibletootherinfections.8,9
Thetreatmentisperformedaccordingtotheclinicalform. Itisrecommendedtomanagepatientswithlessaggressive formsusingsupportivecare,withawatchfulwaitingapproach orantiviralswithzidovudine(AZT)andinterferon-alpha
(IFN-␣) being the most used. In aggressive ATL, patients are
generallytreatedwithchemotherapy,antiviralsand/orbone marrowtransplantation.Othertreatmentprotocolsarebeing testedsuchasmonoclonalantibodiesandarsenictrioxide.5
Objective
Theaimofthis study wastocorrelate survivalwith treat-mentapproachesforthefivedifferentclinicaltypesinBahia,
Brazilandtoevaluatewhatissuesexistedintheirtreatment processes.
Methods
Patientcharacteristics
Thiswasacohortstudyof83ATLpatientswhosedatawere obtainedinanATLdatabaseofthePathologyDepartmentof theUniversityHospitaloftheUniversidadeFederaldaBahia (UFBA).Themajorityofpatientswerediagnosed,treatedand followed-up intheHematology,Dermatologyand Pathology Departments of the hospital. Most of these patients were dependentontheBrazilianNationalHealthSystem(NHS),but 21hadhealthinsuranceplansandcamefromprivate hospi-talsoroutpatientservicesofSalvador,Bahiaforpathological reviewsandstudyadmission.Patientswerediagnosed accord-ingtopreexistentcriteria.5Inpatientswithmoreprolonged survivalorwithlessthan19yearsofage,HTLV-1proviral inte-grationwasinvestigatedusingSouthernblotorlong-inverse polymerasechainreaction(PCR)10,11andallofthempresented monoclonality. All patientswere humanimmunodeficiency virus(HIV)negative.
Initially wehad101patients diagnosedwithATLbut 18 were ineligibleforthe study duetoshort survivalorshort treatmentduration(<1month).Ofthe83selectedpatients, 55 lived in Salvador and 28 inthe interior ofBahia. Mean diseaseduration(timeelapsedfrombeginningofsymptoms untildiagnosis)was24months,54.2%ofpatientswerefemale, medianagewas49.4years(range:9–84years)andtherewas apredominanceofAfro-descendants(88%).Thestudygroup was composed of 26 smoldering, 23 chronic (16 favorable andsevenunfavorable),16acute,13lymphomaandfivePCT patients.Allthesmolderingpatientswerenon-leukemic,did nothavepulmonaryinvolvementandpresentedskinlesions. ATLassociationwithHAM/TSPoccurredin14patients(16.9%).
Treatment
Table1–ClinicalclassificationofadultT-cellleukemia/lymphoma.4,7
Forms Lymphocytosis Abnormallymphocytes(%) LDHlevels Hypercalcemia Involvedorgans
Smolderinga Absent <5or≥5 ≤1.5×N Absent Withorwithoutskin/lunglesions
PCT Absent <5 ≤1.5×N Absent Skin
Chronicb Present Present ≤2×N Absent Anyorganexceptbone,GITandCNS
Lymphoma Absent ≤1 Variable Mayoccur Lymphnodesandanyotherorgan
Acute Usuallypresent ≥5 >1.5×N Mayoccur Anyorgan
a Subtypedintoleukemic(≥5%)andnon-leukemic(<5%)accordingtoabnormallymphocytespercentage.
b Subtypedintofavorableandunfavorableaccordingtotheserumlevelsofalbumin,ureanitrogen,andlacticdehydrogenase(LDH).
PCT:primarycutaneoustumoral;N:normalvalue;GIT:gastrointestinaltract;CNS:centralnervoussystem.
maximum of 115). The type of phototherapy was chosen according to the degree of infiltration of the skin lesions. Only three smoldering patients received either multiagent chemotherapyoretoposidealoneduetogeneralized exfolia-tiveerythroderma.
Antiviral therapy consisted of a combination of AZT, producedbytheInstituteofPharmaceuticalTechnology (Far-manguinhos/FIOCRUZ),and IFN-␣ providedbythe NHS for
homeadministration.ThetypeofIFN-␣,2aor 2b,givento
patientsvariedovertheyears.Currently,IFN-␣2ais
manufac-turedbySheyangLoSunshinePharmaceuticalCo.,Ltd(China) and IFN-␣ 2b by the Institute of Technology in
Immuno-biology Bio-Manguinhos,FIOCRUZ.Both typesare lyophilic intramuscular/subcutaneousinjectionsprovidedinampoules with3,000,000IU.
Chemotherapy consisted of cyclophosphamide, doxoru-bicin, vincristine, and prednisone (CHOP) and CHOP-like regimenswithdosesadjusteddependingontheclinical con-ditionofthepatient;onepatientwastreatedwithaJapanese protocolofchemotherapy.12Patientswho evolvedwith dis-ease progression while using antiviral therapy received chemotherapy. Moreover, patients who evolved with dis-easeprogressionafterfirst-linechemotherapyreceivedeither salvage chemotherapy or salvage antiviral therapy. Only one patient was submitted to bone marrow transplanta-tion.
Clinicalandlaboratorialexams,aswellasimagingtests (ultrasound or computed tomography, X-rayor chest com-putedtomography)wereusedtoevaluatetreatmentresponse.
Statisticalanalysis
ThedatawereanalyzedusingtheIBMStatisticalProgramfor theSocialSciences (SPSS)Software v20.0.Themedian sur-vivaltime(MST)wascalculatedbytheKaplan–Meiermethod, andthelog-rankmethodwasusedtocomparethedifferences betweenthevariousgroups.Forstatisticalpurposes,ap-value <0.05wasconsideredsignificant.
Ethicalaspects
TheResearchEthicsCommittee(CEP)oftheUniversity Hospi-taloftheUniversidadeFederaldaBahia(UFBA)approvedthe researchproject.
Results
First-linetreatment
Completeresponsewasachievedinsevensmolderingpatients with symptomatic treatment, in two favorable chronic patients(onetreatedwithantiviraltherapyaloneandonewith chemotherapyalone),inoneacutecasetreatedwith antivi-ralaloneandinonelymphomacasetreatedwithaJapanese protocol.12
On comparing the 19 smoldering patients who initially were submitted to symptomatictreatment alone, with the seven others who received specific treatment for ATL, the formerpresentedalongersurvival(169monthsvs.52months;
p-value=0.1164) (Figure 1). Of those who received symp-tomatictreatment,only12weresubmittedtophototherapy, sevenofwhomachievedcompleteresponseandfourpartial response. Thesmoldering patientwho receivedmultiagent chemotherapyhadashortersurvivalinrelationtothosewho receivedantiviralsor etoposidealone(Table2).Thepatient whoreceivedetoposideforthreemonthsandlater
AZT/IFN-␣orjustIFN-␣,irregularlyforanothersevenyearsachieved
completeremissionwithasurvivalof240months.Theother patientwhoreceivedetoposideduring12monthsand,dueto diseaseprogression,wastreatedwithAZT/IFN-␣hadpartial
responseandsurvived36months.
TheoverallMSTwas18monthswiththeacute,lymphoma, PCT andunfavorable chronicformshavingshortersurvival (Table2).
TheMSTofthefavorablechronicpatientswho received first-lineantiviraltherapy(44months)waslonger,albeit with-out statisticalsignificance, tothose who received first-line chemotherapy(36months)orfirst-lineantiviralsassociatedto 22monthsofchemotherapy(p-value=0.465,p-value=0.0069 and p-value=0.177, respectively). In contrast, unfavorable chronic patients who received 11 months of first-line chemotherapy had a longer MST, though non-significant, than those who received sixmonths offirst-line antivirals orsixmonthsofchemotherapyassociatedwithantivirals(p -value=0.198,p-value=0.157andp-value=0.639).
Intheacuteform,theMSTofthepatientswhoreceived first-linechemotherapywassuperiortothosewhoreceived simultaneously chemotherapy and AZT/IFN-␣, with a
The survival curves
Cumulative survival
1,0
0,8
0,6
0,4
0,2
0,0
,0 50,0 100,0 150,0 200,0 250,0
Survival (months)
Treatment smoldering form Specific Symptomatic Censured - specific Censured - symptomatic
Figure1–SurvivalcurvesofspecificandsymptomatictreatmentsforsmolderingadultT-cellleukemia/lymphoma.
Table2–First-linetherapyandsurvivalin83patients withadultT-cellleukemia/lymphomaaccordingto clinicaltype.
Clinicaltype First-linetherapy n MST
Smoldering Skindirectedtherapies 19 169
AZT/IFN-␣ 4 52
Chemoa 1 4
Ectoposidealonea 2 36
Total 26 109
Favorablechronic AZT/IFN-␣ 9 44
Chemo 6 36
Chemo+AZT/IFN-␣ 1 22
Total 16 42
Unfavorablechronic AZT/IFN 4 6
Chemo 2 11
Chemo+AZT/IFN-␣ 1 6
Total 7 10.5
Acute AZT/IFN-␣ 7 6
Chemo 8 11
Chemo+AZT/IFN-␣ 1 2
Total 16 6
Lymphoma Chemob 12 7
AZT/IFN-␣ 1 15
Total 13 9
Primarycutaneous tumoral
AZT/IFN-␣ 2 4
Chemo 2 15
Chemo+AZT/IFN-␣ 1 28
Total 5 20
Total 83 18
MST:median survivaltime;AZT:zidovudine; IFN-␣:
interferon-alpha;Chemo:multiagentchemotherapy. a Erythrodermicpatients.
b OneusedtheJapanesechemotherapyprotocol.
p-value=0.005).ComparingtheMSTofthepatientswhoused onlyantiviraltreatmentwiththosewhousedonly chemother-apy, no statistically significant difference was found (six monthsvs.11months;p-value=0.109).Notwithstanding,the patientwithacuteATLtreatedduringtenmonthsexclusively withAZT/IFN-␣achievedacomplete response.Thispatient
wassubmittedtobonemarrowtransplantationbutdiedwith post-transplantcomplications.
Patients with PCT and lymphoma initially received chemotherapy,AZT/IFN-␣orcombinationsofthetwo,
with-out response,exceptforonepatientwhousedsixcyclesof theJapaneseoriginalLSG15(VCAP-AMP-VECP)regimen.This regimenconsistsofvincristine,cyclophosphamide, doxoru-bicin,andprednisolone(VCAP);doxorubicin,ranimustine,and prednisolone (AMP);and vindesine, etoposide, carboplatin, and prednisolone(VECP)withintrathecal administrationof methotrexateandprednisoneasprophylaxisagainstcentral nervous systemrelapse.12 Asranimustinedoes notexistin Brazil,itwassubstitutedbycarmustine.
Fifteen(65.2%)ofthechronicpatients progressedtothe acuteform(71.4%oftheunfavorableand62.5%ofthe favor-ablechronicpatients).Fourpatientswiththesmolderingform progressedtochronicandonetothePCTtype.Twopatients withlymphomaprogressedtotheacuteformofthedisease.
fivemonthswiththistreatmentbeinghaltedthreeyearsago withoutrelapse.ThepatientwhoprogressedtothePCTform receivedantiviraltreatmentfollowedbychemotherapyafter progressionandcontinuedtoalternatethesetreatmentsuntil deathafter46months.
Radiotherapywasusedintwosmoldering patientsafter progressiontothechronicformandPCTwithisolated cuta-neouslesions.In onecase,theirradiatedlesions regressed completelyleavingscars,evenafter20yearsoffollow-up.14 Theotherpatienthadonlyapartialresponse,withlater pro-gressionanddeath.13
Thefavorable chronic patients who onlytook
AZT/IFN-␣ during the course of the disease showed higher MST
whencompared to those who took AZT/IFN-␣ followed by
chemotherapyandthosewhotookthesetherapies simulta-neously(p-value=0.016andp-value=0.046,respectively).In theunfavorablechronicandacutepatients,thecomparisons inthesequenceofdifferenttreatmentsshowednostatistically significantdifferences.
Themortalitywas81.9%(68cases),with15patientsalive attheendofthestudy.Thecauseofdeathwasduetodisease in72%ofthepatients,toothercausesin17.6%andtoother infectionsin7.3%.DeathsduetoATLoccurredin17(80.9%) chronic(75%ofthe favorableand83.3% ofthe unfavorable subtypes),in15(93.75%)acute,inallcasesoflymphomaand PCTandinthree(11.5%)smolderingpatients.Twoofthe smol-deringpatientsdiedduetodiseaseprogressionandtheother duetocomplicationsofexfoliativeerythrodermaresistantto treatment.
Discussion
ATLcomprisesasetofdifferentclinicalformsthathave dif-ferentevolutionsandtherapeuticindications,hencethegreat importanceoftheirproperclassificationbeforeanyguidance ontherapeuticapproaches.
Inthe smoldering form,the MST was superior towhat isdescribed intheliterature7,15,16whichmaybeduetothe useoftheclassificationproposedbyBittencourtetal.,4which separatespatientswithtumorsornodules,inadistinct clin-icalform,thePCT type,unlikeJapaneseauthors.7,15–17 The patientswiththesmolderingformdiedmostlyduetoother causes,contrary towhatwasobservedintheotherclinical types,includingthePCT.Inthisform,watchfulwaitinguntil diseaseprogressionwasviewedasthebestchoice,although therewasnostatisticallysignificantdifferencesintheMSTof thisgroupcomparedtopatientstreatedwithspecific thera-pies.Thismaybeduetothegreaternumberoflivingpatients (censored).
Thedataofthisstudyare consistentwithotherauthors forwhomtargetedtherapiesweregenerallybelieved unneces-saryforthesmolderingformandwherewatchfulwaitingwas consideredthebestoption.15Itshouldberememberedthat 11of19patientsmanagedwithwatchfulwaitinguntildisease progressionweresubmittedtophototherapy,allwitha com-pleteorpartialresponseandthatthisprovedtobeaneffective conductinthe presentstudy.Althoughwatchfulwaitingis themostrecommendedintheliteratureforthesmoldering form,5phototherapyseemstobethebestapproachasitleads
toacompleteorpartialremissionofthecutaneouslesions,as reportedbyotherauthors.15
Patients withthesmoldering typewho receivedspecific treatmenthaderythrodermaandprobablythiswasthereason forphototherapy.Twotooketoposide,withdisease progres-sioninoneandcompleteremissionintheother.Treatment withetoposideassociatedwithphototherapyinthe smolder-ingformisreportedtoincreasesurvival.15
Thesecond best prognosis wasobserved inthe chronic form. Some Japanese authors classify the smoldering and chronic forms as indolent.16 However, it is important to rememberthatthechronicformisclassifiedintofavorableand unfavorablesubtypes,withdifferentsurvivalsandresponses totreatment,5asnotedinthisstudy.
Themostaggressiveforms,lymphoma,acute,unfavorable chronic,andPCThadlowerMST,regardlessofthetherapeutic approachesemployed.
Considering the first-line therapy in chronic and acute patients, no significant differences were observedbetween treatment with antivirals or multiagent chemotherapy. In contrasttothisobservation, Bazarbachietal.8 showedthat first-line antiviral treatment induces a high rate of remis-sionandprolongssurvivalinchronicATL.Notwithstanding, inacuteATL,onlythepatientswithinitialcompleteresponse presentedaprolongedsurvival(5-yearoverallsurvival:82%)8 as observed in the present study. The worst option for theseATLtypeswasthesimultaneoususeofantiviralsand chemotherapy,probablyduetooverlappingsideeffects.
The only patient in this series who underwent bone marrowtransplantationdiedduetopost-transplant compli-cations.Althoughitisarecommendedpracticeforaggressive formsofATL,mortalityisstillhigh.18,19
ThelymphomaATLpatientsdidnotrespondtoantivirals andchemotherapyexceptonewhousedaJapaneseprotocol ofintensive sequencedchemotherapyfollowed byantiviral therapy.12Thispatientisaliveincompleteremissionafter64 months.InJapan,goodresultshavebeenobtainedwiththis protocol.5
Analyzingthetreatmentofthefavorablechronicpatients, they had a higher survival rate with AZT/IFN-␣, while
the worst response was with the simultaneous use of chemotherapyandantivirals.Intheunfavorablechronicform, chemotherapygavebetterresults,butthe smallnumberof casesprecludedanalysis.
However,itwasdifficulttoanalyzetheantiviraltreatment responsebecausethetreatmentwasveryirregularinatleast 50%ofpatients.Itisnoteworthythattreatmentwith antivi-ral drugs isself-administeredathomeand subjecttopoor adherence;asignificantnumber ofthepatientsinterrupted treatmenteitherduetotheirowndecisionsorduetomedical advicebecauseoftheexcessivesideeffects,particularlywith IFN-␣.Sometimes,thetreatmentwastemporarilyinterrupted
owingtoproblemsingettingthedrugsthatwere unavailabil-ityinthehospitalpharmacyasthereisalimitedamountof medicationavailableorbecausepatientswereunabletotravel toSalvadortopickupthemedications.
ofunderstandingabouttheseeffects.Ontheotherhand,there isthepossibilitythatpatientsdidnotuseadequate refrigera-tiontostoretheproducts.
Incontrast,thechemotherapytreatmentwasadministered mainlyduringhospitalizationandtoalesserextent,in out-patient hematologic services. In these cases, only medical personnelinterruptedtreatmentduetolackofresponse,but anothertreatmentplanwassoonestablished.Thus,patients hadcontinuedtreatmentandassistance.Furthermore,most patients who received chemotherapy received a CHOP-like regimen,withreduceddosage,andhence,fewersideeffects.
Amongotherrelevantissues,inBrazil,owingtothe diffi-cultyofaccesstohealthcareservicesandtoignoranceofthe diseasebyprimarycareprofessionals,therewasalargegap (averageof25months)betweentheonsetofsymptomsand diagnosisofATL.Unfortunately,the managementguideon infectionbyHTLVoftheMinistryofHealthstatesthat mul-tiagentchemotherapyistheonlyadjuvanttreatmentinATL, contradictorilywiththe recentinternationalliterature,and, moreover,doesnotindicate the bestapproachforpatients withthesmolderingform.20
Itisnoteworthythatcasesofthemostsevereforms,where survivalisshort,didnotalwayshavetimetobegintherapyas theyoftendiedbeforetreatmentbeganorwithinamonthafter starting,aspectsthatreflectboththegravityofATLandthe delayindiagnosis.Inthepresentseries,thesefactsoccurred in15patients,allofwhomhadlymphomaandacuteATL.
Thesmallnumberofcasesmakesitdifficulttocompare thetreatmentofthefiveformsofATL,inparticularduetothe lackofapre-establishedtreatmentprotocolandthusvarious treatmentregimenswereused.
Itisimportanttoemphasize theneed forregular mon-itoringofATL patients, assome ofthemprogress tomore aggressiveforms,evenduringtreatment.InJapan, smolder-ingATLprogressestotheacuteformmuchmorefrequently thanwasseeninthecurrentstudy.15,16Inthechronicform, ahighnumberofpatients(56.2%)ofthisstudyprogressedto theacuteformasisreportedintheliterature.16
ItwasobservedthatsmolderingandfavorablechronicATL canhavealongsurvivaltime,evenafterdiscontinuingspecific treatmentor phototherapy afterremission ofdisease.This observationwascuriousbecauseitisconsideredthatantiviral treatmentdoesnotcureandtreatmentshouldbe adminis-teredforanindefiniteperiod,evenafterthedisappearanceof symptoms.21 Evenso,thesepatientsshouldcontinuebeing followed-up.
Withthispaper,wehopetogettheattentionofthepublic healthorgans inordertoimprove thecareofATLpatients throughadequatepublichealthpolicies.
Conclusions
Inthesmolderingform,thebestapproachiswatchfulwaiting associatedwithphototherapyuntilprogressionofdisease.
Inthefavorablechronicform,therewasatrendofbetter resultswithAZT/IFN-␣comparedtochemotherapy,
highlight-ingtheimportanceofsub-classifyingthisform.
Although ATL is always considered a serious disease, thereare patientswho havealong survivalwithcomplete remission.
Probablyduetothe lackofknowledgeofthisdiseaseby primaryhealthcaredoctors,ittakestimeforanATLpatientto bediagnosed.
ABraziliantherapeuticprotocolforATLneedstobe estab-lished.Webelievethat moreattention ofthepublichealth organsshouldbegiventoATLinrespecttothevertical trans-missionofHTLV-1infectioninordertoreducethisdiseasein thefuture.
Funding
ThisworkwassupportedbyConselhoNacionaldePesquisa (CNPq)andFundac¸ãodeApoioàPesquisanoEstadodaBahia (FAPESB).
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgments
Theauthorsaregratefultothedermatologistsandoncologists whoprovidedthefollow-updatafromtheirpatients.
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1.GessainA,GoutO,SaalF,DanielMT,RioB,FlandrinG,etal. EpidemiologyandimmunovirologyofhumanT-cell leukemia/lymphomavirustypeI-associatedadultT-cell leukemiaandchronicmyelopathiesasseeninFrance.Cancer Res.1990;5017Suppl.:5692S–6S.
2.DouradoI,AlcantaraLC,BarretoML,daGloriaTeixeiraM, Galvão-CastroB.HTLV-IinthegeneralpopulationofSalvador, Brazil:acitywithAfricanethnicandsociodemographic characteristics.JAcquirImmuneDeficSyndr.
2003;34(5):527–31.
3.Gonc¸alvesDU,ProiettiFA,RibasJG,AraújoMG,PinheiroSR, GuedesAC,etal.Epidemiology,treatment,andpreventionof humanT-cellleukemiavirustype1-associateddiseases.Clin MicrobiolRev.2010;23(3):577–89.
4.BittencourtAL,VieiraMG,BritesCR,FarreL,BarbosaHS. AdultT-cellleukemia/lymphomainBahia.Brazil:analysisof prognosticfactorsinagroupof70patients.AmJClinPathol. 2007;128(5):875–82.
5.TsukasakiK,HermineO,BazarbachiA,RatnerL,RamosJC, HarringtonWJr,etal.Definition,prognosticfactors, treatment,andresponsecriteriaofadultT-cell leukemia-lymphoma:aproposalfromaninternational consensusmeeting.JClinOncol.2009;27(3):453–9.
6.FoucarK.MatureT-cellleukemiasincludingT-prolymphocytic leukemia,adultT-cellleukemia/lymphoma,andSézary syndrome.AmJClinPathol.2007;127(4):496–510. 7.ShimoyamaM.Diagnosticcriteriaandclassificationof
clinicalsubtypesofadultT-cellleukaemia-lymphoma.A reportfromtheLymphomaStudyGroup(1984–87).BrJ Haematol.1991;79(3):428–37.
9. CarvalhoEM,BacellarO,PortoAF,BragaS,Galvão-CastroB, NevaF.Cytokineprofileandimmunomodulationin asymptomatichumanT-lymphotropicvirustype1-infected blooddonors.JAcquirImmuneDeficSyndr.2001;27(1): 1–6.
10.KamihiraS,SugaharaK,TsurudaK,MinamiS,UemuraA, AkamatsuN,etal.ProviralstatusofHTLV-1integratedinto thehostgenomicDNAofadultT-cellleukemiacells.ClinLab Haematol.2005;27(4):235–41.
11.EtohK,TamiyaS,YamaguchiK,OkayamaA,TsubouchiH, IdetaT,etal.Persistentclonalproliferationofhuman T-lymphotropicvirustypeI-infectedcellsinvivo.CancerRes. 1997;57(21):4862–7.
12.KatoK,AkashiK.Recentadvancesintherapeuticapproaches foradultT-cellleukemia/lymphoma.Viruses.
2015;7(12):6604–12.
13.BittencourtAL,BarbosaHS,PimentaA,FarréL.Acaseof adultT-cellleukemia/lymphoma(ATL)withasurvivalof morethan13years.ActaOncol.2008;47(5):981–3.
14.BittencourtAL,BarbosaHS,RequiãoC,SilvaAC,Vandamme AM,VanWeyenberghJ,etal.AdultT-cellleukemia/lymphoma withamixedCD4+andCD8+phenotypeandaindolent course.JClinOncol.2007;25(17):2480–2.
15.SawadaY,HinoR,HamaK,OhmoriS,FuekiH,YamadaS, etal.Typeofskineruptionisanindependentprognostic
indicatorforadultT-cellleukemia/lymphoma.Blood. 2011;117(15):3961–7.
16.TakasakiY,IwanagaM,ImaizumiY,TawaraM,JohT,KohnoT, etal.Long-termstudyofindolentadultT-cell
leukemia-lymphoma.Blood.2010;115(22):4337–43. 17.KatsuyaH,IshitsukaK,UtsunomiyaA,HanadaS,EtoT,
MoriuchiY,etal.ATL–PrognosticIndexProject.Treatment andsurvivalamong1594patientswithATL.Blood. 2015;126(24):2570–7.
18.BazarbachiA,GhezD,LepelletierY,NasrR,deThéH, El-SabbanME,etal.Newtherapeuticapproachesforadult T-cellleukaemia.LancetOncol.2004;5(11):664–72. 19.IshidaT,HishizawaM,KatoK,TanosakiR,FukudaT,
TakatsukaY,etal.Impactofgraft-versus-hostdiseaseon allogeneichematopoieticcelltransplantationforadultTcell leukemia-lymphomafocusingonpreconditioningregimens: nationwideretrospectivestudy.BiolBloodMarrow
Transplant.2013;19(12):1731–9.
20.MinistériodaSaúde.GuiadeManejoClínicodaInfecc¸ãopelo HTLV.Brasília:MinistériodaSaúde;2013.80pp.Available from:http://www.aids.gov.br/sites/default/files/anexos/ publicacao/2014/56099/htlvmanualfinalpdf25082.pdf. 21.Marc¸aisA,SuarezF,SibonD,FrenzelL,HermineO,
