www.jped.com.br
ORIGINAL
ARTICLE
Acute
Myeloid
Leukemia:
analysis
of
epidemiological
profile
and
survival
rate
夽
Mariana
Cardoso
de
Lima
∗,
Denise
Bousfield
da
Silva,
Ana
Paula
Ferreira
Freund,
Juliana
Shmitz
Dacoregio,
Tatiana
El
Jaick
Bonifácio
Costa,
Imaruí
Costa,
Daniel
Faraco,
Maurício
Laerte
Silva
ServiceofPediatricOncology,HospitalInfantilJoanadeGusmão,Florianópolis,SC,Brazil
Received22April2015;accepted5August2015 Availableonline3February2016
KEYWORDS
Acutemyeloid leukemia; Leukemia; Children
Abstract
Objective: Todescribetheepidemiologicalprofileandthesurvivalrateofpatientswithacute myeloidleukemia(AML)inastatereferencepediatrichospital.
Method: Clinical---epidemiological,observational, retrospective,descriptivestudy.Thestudy includednewcasesofpatientswithAML,diagnosedbetween2004and2012,youngerthan15 years.
Results: Of the 51 patients studied, 84% were white; 45% were females and 55%, males. Regarding age,8% wereyounger than1year, 47%were agedbetween 1and 10 years,and 45%wereolderthan10years.Themainsigns/symptomswerefever(41.1%),asthenia/lackof appetite(35.2%),andhemorrhagicmanifestations(27.4%).Themostaffectedextra-medullary sitewasthecentralnervoussystem(14%).In47%ofpatients,thewhitebloodcell(WBC)count wasbelow10,000/mm3atdiagnosis.Theminimalresidualdisease(MRD)waslessthan0.1%, onthe15thdayoftreatmentin16%ofthesample.Medullaryrelapseoccurredin14%ofcases. WhencomparingthebonemarrowMRDwiththevitalstatus,itwasobservedthat71.42%of thepatientswithtypeM3AMLwerealive,aswere54.05%ofthosewithnon-M3AML.Thedeath ratewas43%andthemainproximatecausewassepticshock(63.6%).
Conclusions: Inthisstudy,themajorityofpatientsweremale,white,andolderthan1year. MostpatientswithWBCcount<10,000/mm3atdiagnosislived.Overallsurvivalwashigherin patientswithMRD<0.1%.TheprognosiswasbetterinpatientswithAML-M3.
©2016SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Allrightsreserved.
夽
Pleasecitethisarticleas:deLimaMC,daSilvaDB,FreundAP,DacoregioJS,CostaTE,CostaI,etal.AcuteMyeloidLeukemia:analysis
ofepidemiologicalprofileandsurvivalrate.JPediatr(RioJ).2016;92:283---9.
∗Correspondingauthor.
E-mail:[email protected](M.C.deLima).
http://dx.doi.org/10.1016/j.jped.2015.08.008
PALAVRAS-CHAVE
Leucemiamielóide aguda;
Leucemia; Crianc¸a
LeucemiaMielóideAguda:análisedoperfilepidemiológicoetaxadesobrevida
Resumo
Objetivo: DescreveroperfilepidemiológicoeataxadesobrevidadospacientescomLeucemia MielóideAguda(LMA),emumhospitalpediátricodereferênciaestadual.
Método: Estudoclínico-epidemiológico,observacional,retrospectivoedescritivo.Foram incluí-doscasosnovosdepacientescomLMA,diagnosticadosentreosanosde2004e2012,comidade
<15anos.
Resultados: Entreos 51 pacientesestudados, 84%eram darac¸a branca, 45%do sexo femi-ninoe 55%domasculino.Quantoafaixaetária,8% tinhamidade<1ano, 47%entre1e10
anose,45%>10anos.Osprincipaissinais/sintomasaodiagnósticoforamfebre(41,1%), aste-nia/inapetência(35,2%)emanifestac¸õeshemorrágicas(27,4%).OSistemaNervosoCentralfoio localextra-medularmaisacometido(14%).Em47%dospacientesaleucometriaaodiagnóstico foi<10.000/mm3.Adoenc¸aresidualmínima(DRM)no15◦diadetratamentofoi<0,1%em16%
dacasuística.Recidivamedularocorreuem14%doscasos.AosecompararaDRMdamedula ósseacomostatusvital,observou-sequeestavamvivos71,42%dospacientescomLMAtipoM3 e54,05%daquelescomLMAnão-M3.Ataxadeóbitofoide43%eaprincipalcausaimediatafoi ochoqueséptico(63,6%).
Conclusões: Nesteestudo,amaioriadospacientesédosexomasculino,rac¸abranca,maiores que1anodeidade.Amaioriadospacientescomleucometria<10.000/mm3aodiagnósticoestá viva.A sobrevida globalémaiornospacientescomDRM <0,1%.Oprognósticoémelhornos pacientescomLMA-M3.
©2016SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Todososdireitos reservados.
Introduction
Acute myeloid leukemia (AML) is a clonal disease of hematopoietictissuecharacterizedbyabnormal prolifera-tionofprogenitorcellsofmyeloidlineage,resultinginthe insufficientgenerationofnormalmaturebloodcells.1
It represents approximately15---20% of acuteleukemia
casesinchildhood,1 andaccountsforabout 30%ofdeaths
inthisagerange.2InBrazil,itsestimatedincidenceis400
casesperyear.3
Hemorrhagic manifestations,fever, and pallor are
fre-quentsymptomsofthediseaseatdiagnosis.Themaincauses
ofdeathareinfections,bleedingepisodes,leukostasis,and
tumorlysissyndrome.4
The main factors affecting the mortality rateof these
patientsarethoseresultingfromtherapyintensificationand
diseaserelapse.5,6
AMLprognosisimprovementhasbeen madepossibleby
disease stratification into risk groups based on
cytogene-tics,theevaluationofearlyresponsetotreatment,andthe
identificationofchemotherapy-inductionfailure.Currently,
thelikelihoodofAMLcureindevelopedcountriesisaround
60%.7,8
Considering that in recent decades there has been
progress in the introduction of new chemotherapy
treat-ment protocols for AML and that the information in the
pediatric population and its clinical outcomes are still
scarce, this study aimed to analyze the eight-year
expe-rience in a pediatric oncology service, in the South of
Brazil.
Methods
This was a clinical---epidemiological, observational, ret-rospective, descriptive study approved by the Ethics Committee onHuman Research of Hospital Infantil Joana deGusmão(HIJG).
ThestudyincludedallnewcasesofAMLpatientsyounger than 15 yearstreated in HIJG between January 2004 and August2012.
Exclusioncriteriawerelosstofollow-up;patienttransfer toanotherservice;insufficientdataatthehospitalcancer registry andmedicalrecords andstatistics department of HIJG.
The diagnosis of AML was based on morphology, cyto-chemistry, and immunophenotyping by flow cytometry of bonemarrowaspirateand/orperipheralblood,performed with EuroFlow 8-color antibody panels (EuroFlow-ESLHO, Rotterdam, NL). The minimal residual disease (MRD) was analyzed by flow cytometryin the bone marrow after 15 daysofinductiontreatment.Thetreatmentprotocolsused werefromtheInternationalBerlin-Frankfurt-Münster(BFM) StudyGroup AML-83(n=6),AML-98(n=22),andAML-2004 (n=23).
Theanalyzedvariableswereageatdiagnosis(agerange stratified as<1 year, 1 year to 10 years,and >10 years);
Florianópolis,NorthernSantaCatarina,WesternSanta Cata-rina, Mountain Region,SouthernSanta Catarina, Valleyof Itajaí)andothers(fromotherstates);predominantsignsand symptomsat diagnosis (fever, bone pain, abdominalpain, enlargedlymphnodes,hemorrhagic manifestations, gingi-valhypertrophy,pallor,asthenia/lackofappetite,swelling ofsofttissue,andrespiratory symptoms);laboratory find-ingsatdiagnosis(whitebloodcellcount,neutropenia,and platelet count); extramedullary involvement at diagnosis (CNS or other sites); AML classification according to the French---American---British group (FAB)1; presenceand type
of laboratory geneticalterations; presence or absenceof
clinicalandlaboratoryremissionafterthefirst
chemother-apyinduction,accordingtotheMRDvalueonthe15thday
ofinduction,obtainedbyflowcytometry;vitalstatus(alive
ordeceased);death(inremissionornotfromneoplastic
dis-ease),immediatecauseofdeath;presenceandlocationof
diseaserecurrence(bonemarrow,extramedullary,or
com-bined);andbonemarrowtransplantation.
Thestatisticalproceduresusedinthestudywere
descrip-tivemeasures,frequencytables,andPearson’schi-squared
test, with 95% of significance (p<0.05) to analyze, asan
exploratory characteristic, the association between two
variables.Associationswereverifiedbetweenthevariables
vitalstatusandwhitebloodcellcount,vitalstatusandtype
M3-AMLMRD,andvitalstatusandnon-M-AMLMRD.
Results
Of the 51 patients, 55% (n=28) were males and 45% (n=23)females,ataratioof1.2:1.Whitespredominated, accountingfor 84% of patients. Brown and blackpatients represented16%ofthesample.
Meanageatdiagnosiswas7.3years(SD±4.8years)with amedianof9years.Theyoungestageatdiagnosiswas19 daysandtheoldest,14years.Regardingtheagerange,8% ofthesamplewereaged<1year,47%werebetween1and 10years,and45%were>10years.
Asfortheorigin,accordingtothemesoregionsofSanta Catarinaby IBGE,29%were fromthecity of Florianópolis (n=15), 24% were from the Western Region (n=12), 20% fromtheMountain Region(n=10),10% fromtheNorthern Region(n=5),8%fromtheSouthernRegion(n=4),8%from the ItajaiValley (n=4), and2% (n=1) werefrom another state,Paraná.
Themainsignsandsymptomsatdiagnosisaredescribed inTable1.
Atdiagnosis,24%ofpatientshadextramedullarydisease
(n=12),and themost oftenaffected sitewasthe central
nervous system (CNS) in 14% (n=7). The other 10% had
skininvolvement(n=2),boneinvolvement,andsofttissue
edema(n=3).
LaboratorydataatAMLdiagnosis(leukocytes,platelets,
andneutropenia) andmorphological FAB classificationare
describedinTable2.
WhencorrelatingWBCcountatdiagnosiswithvital
sta-tus(p=0.014),itwasobservedthat79.2%ofpatientswith
WBCcount<10,000lived,whereas29.4%ofthosewithWBC
countsbetween10,000and50,000lived.Thethreepatients
(6%)thathadWBCcount>100,000died.
The study of geneticdisorderswasdocumentedin51%
ofpatients(n=26),showingalterationsin46.15%of cases
Table 1 Signs andsymptoms atdiagnosis in number (n) andpercentage(%)ofpatientswithacutemyeloidleukemia treatedinHospitalInfantil JoanadeGusmão(HIJG),from 2004to2012.
Signs/symptoms n %
Pallor 13 25.40%
Hemorrhagicmanifestations 14 27.40%
Fever 21 41.10%
Asthenia/lackofappetite 18 35.20% Increaseinsofttissuevolume 4 7.80%
Bonepain 11 21.50%
Abdominalpain 2 3.90%
Adenomegaly 2 3.90%
Gingivalhypertrophy 3 5.80% Respiratorysymptoms 4 7.80%
Table2 Hematologicalalterationsand French---American---British(FAB)classificationatdiagnosisofpatientswithacute myeloid leukemia treated at Hospital Infantil Joana de Gusmão(HIJG),from2004to2012.
Hematologicalalterations n %
Whitebloodcellcount
<10,000 24 47%
10,000---50,000 17 33%
>50,000---100,000 4 8%
>100,000 3 6%
Notmentioned 3 6%
No.ofplatelets
<20,000 11 22%
20,000---100,000 29 57%
>100,000 8 16%
Notmentioned 3 6%
Neutropenia
Yes 21 41%
No 27 53%
Notmentioned 3 6%
FAB n %
M0 6 12%
M1 1 2%
M2 14 27%
M3 14 27%
M4 8 16%
M5 4 8%
M6 1 2%
M7 3 6%
(n=12). Themost frequentalterationwast(15;17), found insixpatients(23%).Oneofthesepatientshadan associa-tionoft(15;17)withFLT3-ITDmutation.The othergenetic disordersfound werepolyploidy, t(8;21), presenceof MLL rearrangement,t(3;5)deletionofchromosome18,trisomy ofchromosome21,trisomyofchromosome8,andtetrasomy ofchromosome8.
Table3 Minimalresidualdisease(MRD)inbonemarrowonthe15thdayoftreatmentofacutepromyelocyticleukemia(M3-AML) andvitalstatusofpatientstreatedatHospitalInfantilJoanadeGusmão(HIJG),from2004to2012(p=0.025).
MRD Vitalstatus
Alive Dead Total
n % n % n %
<0.1% 6 42.85% 0 0 6 42.85%
0.1---1.0% 1 7.14% 0 0 1 7.14%
>1.0% 3 21.44% 1 7.14% 4 28.58%
Notmentioned 0 0 3 21.44% 3 21.44%
Total 10 71.42% 4 28.58% 14 100%
>1.0%;14%(n=7)ofthecaseslackedthetestresultinthe medicalrecord.
ThecomparisonbetweenthebonemarrowMRD,onthe 15th day of treatment and the vital status of patients with acute promyelocytic leukemia (M3-AML) and acute non-promyelocytic leukemia (non-M-AML) is described in Tables3and4.
Overallsurvivalwas57%inthisstudy.Bycorrelatingvital
statuswith M3-AML andnon-M-AML, it wasobserved that
71.42%and54.05%ofthepatientswerealive,respectively,
attheendofthestudy.
Of the patients who died (n−22), 64% (n=14) were
notin complete clinicalremission ofleukemia at theend
ofchemotherapyinduction. The mainimmediatecauseof
deathwassepticshockin63.6%ofpatients(n=14).Ofthe
deaths, three occurred within the first 15 days of
treat-ment,onefromintracranialhemorrhage(M3-AML)andthe
othertwo,inadditiontosepsis,hadpulmonaryleukostasis
andintracranial hemorrhage withspinal fluid infiltrate at
diagnosis,respectively.
Regarding thedeaths that occurredafter the 16thday
ofinduction treatment (n=19), 12occurred duetoseptic
shock. Of these, six occurred after chemotherapy
re-inductionforrecurrence.
Ofpatients withWBCcount>100,000, onepatienthad
M3-AML,whoseimmediatecauseofdeathwassepticshock,
anotherhadM0-AMLwithpulmonaryleukostasisassociated
withseptic shock, and the other had M5-AML with acute
renalfailure.
Regarding the patients (n=6) that had t(15;17)
muta-tions,twodied.Thepatientthathadt(15;17)andFLT3-ITD
mutationswasaliveandinremissionuntilthedateof
com-pletionofthisstudy.
Amongtheassessedpatients,39%(n=20)weresubmitted
toradiotherapyand16%(n=8)tobonemarrow
transplan-tation (BMT). Of the patients who underwent BMT, two
diedandtheothersarealiveandincompleteremissionof
leukemia.
In14%ofcases(n=7)therewasdiseaserecurrenceinthe
bonemarrowand,ofthese,sixpatientsdied.
Discussion
Inthisstudy,mostpatientsweremaleandolderthan1year. MostofthosethathadWBCcount<10,000/mm3atdiagnosis arealive.
OverallsurvivalishigherinpatientswithMRD<0.1%and theprognosisisbetterinpatientswithM3-AML.
In other studies,9,10 male gender also showed a slight
predominancetofemales(1.2:1).
As in the study by Kavcic,10 it wasobserved that AML
predominated in whites. In Santa Catarina, asa result of
thewhitedescentofthemajorityofthepopulation,white
ethnicitywaspredominant,makingitimpossibletoestablish
comparisonsbetweentheethnicgroups.
Corroborating other studies,10---12 this study showed a
higherprevalenceofAMLintheagerange>1yearold.
Thisstudy,asin theliterature,alsodemonstratedthat
the signs and symptomsof AML resultfrom bone marrow
infiltration,withhemorrhagicmanifestations,fever,
asthe-nia,pallor,andbonepain.2
Inpreviously published studies,the percentage of CNS
involvementatdiagnosisrangedfrom5%to15%.2,13 Inthis
study, 14% of patients had CNS involvement at diagnosis,
similarlytowhatwasdescribedbyRubnitzetal.13
Studieshaveshownthatthepercentageofpatientswith
WBCcounts>100,000/mm3isbetween12%and15%.6,9,14 In
thisseries,only6%ofcaseshadthiselevatedWBCcountat
diagnosis. Thisdifferencecanbe explainedby thelack of
dataavailableinthemedicalrecordsofsomepatients,the
sizeofthissample,ortheearlierdiseasediagnosis.
WBCcount is themost important riskfactor for
treat-ment failure, due to the possibility of causing bleeding
complications or respiratory failuredue to leukostasis.9,15
The present study showed that 80% of patients had WBC
count <50,000/mm3 at diagnosis, similar to the study by
Imamuraetal.14
Theprobabilityofevent-freesurvival(EFS)infiveyears
was only 23% in patients with WBC count >100,000/mm3
accordingtotheanalysisoftheBFM-83andBFM-87
treat-ment protocols.9 This study showed that 79.2% of the
patients(p=0.014)withWBCcount<10,000/mm3at
diag-nosislived,whereasamongthosewithWBCcountsbetween
10,000 and 50,000/mm3, only 29.4% lived. Only three
patients in this study had a WBC count >100,000/mm3
at diagnosis, thus making the statistical analysis
impossible.
TheFABmorphologicalclassificationfor AMLcandefine
treatmentandriskgroupstratification.3Inpreviously
pub-lished studies9,14,16 themost frequentlyidentified subtype
wasM2,ranging from33.6% to37%. In thepresent study,
themostprevalentmorphologicaltypeswereM2(27%)and
Table4 Minimalresidualdisease(MRD)inbonemarrowonthe15thdayoftreatmentofnon-acutepromyelocyticleukemia (non-M3-AML)andvitalstatusofpatientstreatedatHospitalInfantilJoanadeGusmão(HIJG),from2004to2012(p=0.019).
MRD Vitalstatus
Alive Dead Total
n % n % n %
<0.1% 13 35.14% 4 10.81% 17 45.95%
0.1---1.0% 5 13.51% 3 8.11% 8 21.62%
>1.0% 2 5.40% 6 16.22% 8 21.62%
Notmentioned 0 0 4 10.81% 4 10.81%
Total 20 54.05% 17 45.95% 37 100%
Aftertheadventofall-trans-retinoicacid(TRA),M3-AML becametheFABsubtypewiththebestprognosis,byinducing thedifferentiationofleukemicprecursorsintomaturecells, controlledbythisdrug.1,17Thepresentstudyalsofoundgood
therapeutic response tothis medication, considering that
71.42% ofpatients withM3-AMLand 54.05%of thosewith
non-M3-AMLwerealiveattheendofthisstudy.
AMLisaheterogeneousdiseasefromthemolecularpoint
of view,including somaticandepigenetic alterations that
contribute to myeloidleukemogenesis. These cytogenetic
abnormalities,somaticmutations, andtheinduction
ther-apyresponseareimportantinformationforriskstratification
andadequatetherapyallocation.18
Chromosomal abnormalities in AML include aberrations
describedasgainorlossofwholechromosomes structural
abnormalities or balanced translocations.19 The literature
reports that the translocation t(8;21) is the most
preva-lent, varying between 12%and 23%,12---14 whereast(15;17)
isobservedin3.4---10%ofcases.12,13
According to the present results, 46% of the assessed
patients havesome cytogenetic alteration,and
transloca-tiont(15;17)wasmostprevalent(23%),whichisjustifiedby
thenumberofcasesofM3-AMLinthisstudy.Asthis
alter-ationhasafavorableprognosis,it confirmsthefindingsof
increasedsurvival in patientswithM3-AML. Itis
notewor-thy that thecytogenetic analysisof patients in thisstudy
was documented in only 51% of cases, which might have
underestimatedtheresults.
Arecentstudy15 statedthatsurvivalispoorinpatients
withtranslocationt(15;17)andFLT3-ITDmutation
associa-tion,thusrepresentinganindependentprognosticpredictor,
withaprogression-freesurvivalrateof16%.Inthepresent
series,onlyonepatientwithM3-AMLhadthetranslocation
t(15;17)andFLT3-ITDassociation,andwasaliveandwithout
signsofrelapseattheendofthestudy.
In the BFM study, bone marrow MRD measured after
thefirsttreatmentcoursewasthebestevent-freesurvival
predictorwhencomparedtotheriskclassificationscheme
by FAB subtype, cytogenetics, and the presence of blasts
in peripheral blood morphology on the 15th day of
anti-neoplastictreatment.15ThepresenceofhighMRDafterthe
firstcourseofinductionwassignificantlyassociatedwithan
adverseoutcome.Therecurrenceratewasparticularlyhigh
(49%)inpatientswithMRD>1%,whileinpatientswithlower
MRD(0.1---1%),theratewasonly17%.15
The study by Al-Mawali et al.20 also demonstrated
that MRD >0.15% was an independent predictor of poor
prognosisafterchemotherapyinduction.Otherstudieshave
alsodemonstrated a correlation between MRD <0.1% and
improvedevent-freesurvival,suchasthestudybyRubnitz
etal.21andInabaetal.22,23
AlthoughMRDisastrongprognosticfactor,approximately
25%ofpatientswithlowMRDwillhavediseaserecurrence.
ThestudybyKaroletal.24identified,amongtheriskfactors
forrecurrence,certain11q23abnormalitiessuchast(6;11)
andt(10;11),megakaryocyticleukemiawithoutt(1:22),and
age≥10years.24
Inthisstudy,whencomparingtheMRD<0.1%onthe15th
dayoftreatmentwithvitalstatus,itwasobservedthat100%
ofpatientswithM3-AMLand76.5%ofpatientswith
non-M3-AMLwerealive,respectively. WhenMRDwas>1.0%,itwas
observedthat75%ofM3-AMLpatientsand25% of
non-M3-AMLpatientswerealive.Therewasastatisticalsignificance
betweenbonemarrow MRDandvitalstatus (p=0.022), as
wellasbetweenM3-AMLandvitalstatus(p=0.025)and
non-M3-AMLandvitalstatus(p=0.019).Thesedatacorroborate
theprognosticimportanceofMRDquantification.
Regardingrecurrence,thebonemarrowisthemost
fre-quentsiteofAML relapse.15 In thisseries,allrecurrences
occurredatthissite.
Recentantineoplastictherapies,suchasnew
chemother-apeuticagents,monoclonalantibodies,and
immunomodu-lators,arechallengesintheassessmentoftheimpactonthe
child’simmunefunctionandofinfectiouscomplications.19
Theliteraturereportsthattheleadingcauseofdeathin
thesepatientsisinfection,andthatitismainlyrelatedto
chemotherapyintensification.5,6,9
A study by Silva etal.,25 analyzing mortality trends in
Brazilin childrenwithleukemia inthe 1980---2010 period,
reports that the deaths associated to the treatment of
acute myeloid leukemia in less developed countries can
reachup to 33%, asthe intensive chemotherapy regimen
predisposestosevereneutropeniaandexposespatientsto
infections.
Pediatric patients treated for AML are at high risk for
infectiouscomplications,predominantlybacterialand
fun-gal.Someinstitutions haveimplemented prophylaxis with
antibioticandanti-fungalagents,aimedatreducingthese
infections.However,thesystematicevaluationofantibiotic
prophylaxisstudiesindicatesthatthereisinsufficientdata
todefineguidelinesfortheiruse.Therefore,additional
stud-ies are needed to accurately identify the best antibiotic
regimen,aswell asfor whichpopulation of children they
Thepresentstudyalsoshowedthatsepticshock(63.6%)
wasthemostprevalentcauseofdeath.Ofthe19patients
thatdied afterthe 15thday of theinduction therapy,six
hadrelapsed.Thedeathsthatoccurredinthisperiodwere
probablyduetoinfectionsafteraplasiainduction.
In recent decades,in spite of the improved AML
prog-nosis,approximatelyone-thirdofpatientshadrecurrence.
This population hasa poor prognosis, withlong-term
sur-vivalprobabilityofapproximately35%, despitethe useof
intensivechemotherapyandallogeneicbonemarrow
trans-plantation. The toxicity and mortality resulting fromthis
treatmentarealsosignificant.28
Currently, studies with targeted therapies are being
developed, focusingprimarily onthe functional pathways
of leukemic cells, such ascell surface receptors, specific
intracellularkinases,proteinsthatregulatecelldeathand
geneexpressionmodulators,aimingtoimproveAMLpatient
survival.29
AML treatment should bebased ona clinical structure
capable of supporting the therapeutic aggressiveness, in
additiontoa laboratory structure capable of
discriminat-ingtheriskgroupsandcontributingtotheidentificationof
relevantprognosticfactors,aswellasprovidingsupportive
measuresforthecareofthesepatients.
Inthisseries,selection biaswasconsidereddue tothe
inclusionofallcasesdiagnosedattheservice.Theseresults
mayhavebeeninfluencedbycharacteristicsoftheassessed
population;thedifferent treatmentprotocolsused(BFM);
theavailablemedicalandhospitalresourcesinthisservice;
and the sample size. However, the results observed in
thisstudyshowtheneedtoperformnational,multicenter,
analyticalstudies,aiming at confirmationof theobserved
associations and thus, establishing prognostic factors for
AML.
Inthisstudy,thecomparisonofbonemarrowMRDonthe
15thday of induction treatment withvital statusshowed
that 71.42% of patients with typeM3 AML and 54.05% of
thosewithnon-M3-AMLwerealive.Thedeathratewas43%
andthemainimmediatecausewassepticshock(63.6%).
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgement
TheauthorswouldliketothankHospitalInfantilJoanade Gusmão,Florianópolis,SC,Brazil.
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