www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
REVIEW
ARTICLE
Sinusitis
in
patients
undergoing
allogeneic
bone
marrow
transplantation
---
a
review
夽
Joanna
Ewa
Drozd-Sokolowska
a,
Jacek
Sokolowski
b,∗,
Wieslaw
Wiktor-Jedrzejczak
a,
Kazimierz
Niemczyk
baTheMedicalUniversityofWarsaw,OncologyandInternalDiseases,DepartmentofHematology,Warsaw,Poland bTheMedicalUniversityofWarsaw,DepartmentofOtorhinolaryngology,Warsaw,Poland
Received15September2015;accepted19February2016 Availableonline22April2016
KEYWORDS
Sinusitis;
Sinusitistreatment; Hematopoieticstem celltransplantation; Bonemarrow transplantation
Abstract
Introduction:Sinusitis is a common morbidity in general population, however little is knownaboutitsoccurrence inseverely immunocompromisedpatientsundergoingallogeneic hematopoieticstemcelltransplantation.
Objective: Theaimofthestudywastoanalyzetheliteratureconcerningsinusitisinpatients undergoingallogeneicbonemarrowtransplantation.
Methods:An electronicdatabasesearchwasperformedwiththeobjectiveofidentifyingall originaltrialsexaminingsinusitisinallogeneichematopoieticstemcelltransplantrecipients. ThesearchwaslimitedtoEnglish-languagepublications.
Results:Twentyfivestudies,publishedbetween1985and2015wereidentified,noneofthem beingarandomizedclinicaltrial.Theyreportedon31---955patients,discussingdifferentissues i.e.valueofpretransplantsinonasalevaluationanditsimpactonpost-transplantmorbidityand mortality,treatment,riskfactorsanalysis.
Conclusion: Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practicecould be made. First, itseems advisable toscreen all patientsundergoingallogeneichematopoieticstemcelltransplantationwithComputed Tomo-graphy(CT)priortoprocedure.Second,patientswithsymptomsofsinusitisshouldbetreated beforehematopoieticstemcelltransplantation(HSCT),preferablywithconservativemedical approach.Third,patientswhohaveundergonehematopoieticstemcelltransplantationshould bemonitoredcloselyforsinusitis,especiallyintheearlyperiodaftertransplantation. © 2016 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
夽 Please citethisarticle as:Drozd-SokolowskaJE,Sokolowski J,Wiktor-JedrzejczakW, NiemczykK. Sinusitis inpatientsundergoing allogeneicbonemarrowtransplantation---areview.BrazJOtorhinolaryngol.2017;83:105---11.
∗Correspondingauthor.
E-mail:[email protected](J.Sokolowski).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.
http://dx.doi.org/10.1016/j.bjorl.2016.02.012
PALAVRASCHAVE
Sinusite; Tratamentoda sinusite;
Transplantedecélula tronco
hematopoiética; Transplantede medulaóssea
Sinusiteempacientessubmetidosatransplantealogênicodemedulaóssea---uma revisão
Resumo
Introduc¸ão:Asinusiteéumadoenc¸acomumnapopulac¸ãoemgeral,porémpoucosesabesobre a suaocorrência em pacientes gravemente imunocomprometidos submetidos a transplante alogênicodecélulas-troncohematopoiéticas.
Objetivo:Oobjetivodoestudofoianalisaraliteraturasobresinusiteempacientessubmetidos atransplantealogênicodemedulaóssea.
Método: Umabuscanabasededadoseletrônicafoirealizada comoobjetivode identificar todososartigosoriginaisqueinvestigaramsinusiteemreceptoresdetransplantealogênicode células-troncohematopoiéticas.Abuscafoilimitadaapublicac¸õesemlínguainglesa. Resultados: Foramidentificados25estudos,publicadosentre1985e2015,sendoquenenhum deleseraumensaioclínicorandomizado.Elesincluíram31-955pacientes,discutindodiferentes questões,ouseja,valordaavaliac¸ãosinonasalpré-transplanteeseuimpactonamorbidadee mortalidadepós-transplante,tratamento,análisedefatoresderisco.
Conclusão:Os resultados dos estudos analisados produziram resultados inconsistentes. No entanto, algumas recomendac¸ões para boas práticas poderiam ser feitas. Em primeiro lugar,pareceaconselhávelavaliartodosospacientessubmetidosatransplantealogênicode hematopoiéticascomtomografiacomputadorizada(TC)antesdoprocedimento.Em segundo lugar,ospacientescomsintomasdesinusitedevemsertratadosantesdeumTransplantede Células-TroncoHematopoiéticas(TCTH),depreferênciacomabordagemclínicaconservadora. Emterceirolugar,ospacientesquesesubmeteramaTCTHdevemsercuidadosamente moni-torizadosparasinusite,especialmentenoperíodoinicialapósotransplante.
© 2016 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Bonemarrowtransplantation is usedtotreat a varietyof
hematologicaldisorderseitherneoplasticornon-neoplastic.
Both, these primary disorders and aforementioned
treat-ment induce profound immunosuppression affecting
non-specificandspecific immunityincludingboth humoraland
cellulareffectorsmechanisms.Astheconsequence,thereis
anincreasedincidenceofdifferenttypesofinfectionsinthe
post-transplantperiod,whichhave been extensively
stud-ied.However,paranasalsinusitis,whichisoneofthemost
commoninfectionsin generalpopulation,hasbeen
evalu-atedonly in afew trials.Similarly onlyincidental reports
concerninvasivefungalsinusitis,which istypically
associ-atedwithbonedestructionintheaffectedarea.According
toa few published papers sinusitis affects approximately
5---44% of all patients in the post-transplantation period,
mostlyduringtheearlypost-transplantphase.1---6Thereare
nowelldefinedriskfactorsofacutesinusitisandflareups
of chronic sinusitis in hematopoietic stem cell transplant
recipients.
Pretransplantsinus diseaseassessment byCTscanshas
become standard practice in majority of transplant
cen-ters,however,onlylimiteddataexist3,7---9ontheimpactof
pretransplantsinusdiseaseassessedbyCTscansonthe
post-transplantation morbidity and mortality with two studies
limited to children.10,11 No guidelines concerning
treat-mentof chronic sinusitis priortoallogeneic bone marrow
transplantation exist, although earlier studies advocated
aggressivesurgicalintervention.12
Therefore,we decidedtoreviewthedataonsinus
dis-easeinavailableliteratureinrelationtothebonemarrow
transplantation.
Data
sources
and
review
methods
We haveperformed searches ofPubMed,EMBASE and
Sci-ELO database using key words: sinusitis, sinus disease,
hematopoietic stem cell transplantation, bone marrow
transplantation, invasive fungal sinusitis andidentified 25
studiesassessingsinusitisinbonemarrowtransplant
recip-ients. Allresearchwerenon-experimentalanddescriptive
withIIIcategoryofevidence.13
Study
population,
type
of
stem
cell
transplantation
Themajorityofthereviewedstudieswereperformedinthe
late 1980’s and 1990’s. The number of analyzed patients
rangedbetween31and955(Table1).Thetypeofanalysis
differedbetweenstudies.Whilesomeresearchersanalyzed
theentirepopulationofthetransplantedpatients,1,3,4,14---16
some analyzed solely patients who developed sinusitis
or patients for whom CT scans were available and the
exact number of transplanted patients from whom they
have been selectedremains unknown.2,17 Analyzedgroups
contained both allogeneic and autologous hematopoietic
Table1 Time,typeofanalysis,numberofpatientsundergoingbothauto-andallo-HSCT,diagnosis.
Reference Timeandtypeofanalysis Noofpatients withHSCT
Noofpatientswithdifferent diagnoses
TypeofHSCT
AML ALL CML Other Allo Auto
Savageetal.2 Aug1993---Dec1995;
retrospective
NA(44pts.with sinusitis)
NAAL-2 NA 41 1 44 0
Yeeetal.14 Aug1989---Oct1991;
retrospective
136(178BMTs) NA NA NA NA NA NA
Thompsonetal.15 Jan1998---Jun1999;
retrospective
100 19 7 15 59 100
---Shibuyaetal.1 Aug1987---Jul1989;
retrospective
107 18 12 18 59 63 44
Billingsetal.10 Jan1992---Dec1997;
retrospective
51(children) 20 9 NA NA 35 19
Moelleretal.7 Jul2006---Oct2009;
retrospective
71 24 9 6 32 71
---Ortizetal.8 2003---2004;prospective 31 NA NA NA NA 28 3
Wonetal.3 1996---2003;retrospective 252 73 20 37 122 128 124
Fulmeretal.9 Jan2003---Jun2009;
retrospective
228 79 9 11 140 194 43
Johnsonetal.16 Apr1983---Jul1992;
retrospective;onlyfungal sinusitisanalyzed
955 NA NA NA NA NA NA
Bentoetal.4 1996---2011;retrospective 95 12 8 45 28 81 13
Sekineetal.6 Sep2005---Sep2007;
retrospective
85(childrenand adults)
NA NA NA NA NA NA
Arulrajahetal.17 2002---2004;retrospective NA(64with
availableCT; children)
NA NA NA NA 52 12
Zamoraetal.11 2006---2010 100 24 13 3 60
Kasowetal.25 Jan2004---Dec2005;
retrospective
184(children; 187BMTs)
NA NA 10 NA 131 56
Dhongetal.5 Jan1995---Dec1998;
retrospective
34 NA NA NA NA NA NA
AML,acutemyeloidleukemia;ALL,acutelymphoblasticleukemia;CML,chronicmyelogenousleukemia;NA,notavailable.
leukemia constituted from3% to 93% of diagnoses of the
transplantedpatients.1,2,4,9,11,14,15Patientstransplantedfor
pediatric oncology indications were also included in the
severalanalyzed studies(chorioncarcinoma, sarcoma,and
neuroblastoma1; neuroblastoma10; neuroblastoma, Ewing
sarcoma,braintumors).11
Definition
of
sinusitis
At present, European Position Paperon Rhinosinusitis and
Nasal Polyps (EPOS) guidelines are usedfor the diagnosis
of sinusitis.18 In order to diagnose rhinosinusitis
accord-ing to these criteria the patient must present at least
twosymptoms.Oneof themshouldbeeither nasal
block-age/obstruction/congestionandnasaldischarge(anterioror
posteriornasaldrip),whiletheothermaybe:facialpainor
pressure,reductionorlossofsmell.Theclinicalsymptoms
mustbeaccompaniedbyendoscopicchanges(nasalpolyps,
mucopurulent discharge primarily from middle meatus,
edema,mucosalobstructionprimarilyinmiddlemeatus)or
radiologicalchangesinCTscans(mucosalchangeswithinthe
osteomeatalcomplexand/orsinuses)(Fig.1).
The majority of reports concerning sinusitis in
hematopoietic stem cell transplant recipients have
beenpublishedbeforeEPOScriteriahavebeenestablished.
Therefore,criteriautilizedindifferentstudieswillbe
dis-cussedindetail.Itmustalsobekeptinmind,thataccording
tosomeauthors,19 sinusitismayhaveatrulyoccultcourse,
withonlypersistent feverwithradiologicalchanges,or at
least less symptomatic course than in immunocompetent
counterpartsasshownbyArulrajahetal.,17whichisnotin
linewiththecurrentlyuseddefinition.
Savage etal.definedsinusitisasthe presenceof
clini-calsymptomsincombinationwithradiologicalfindingssuch
as:fluidlevel,completesinusopacification,mucosal
thick-ening>5mmin twoormoresinuses. Chronicsinusitiswas
diagnosedwhentherewaslittle symptomatic/radiological
improvementorifsymptomsrecurredafter3ormoreweeks
ofantimicrobialtherapy.2
Thompsonetal., diagnosedacutesinusitisin the
pres-enceof symptoms, such asblockage or congestion, nasal
discharge,hyposmia,facialpressureorpain.15
Shibuya etal. definedsinusitisas clinical symptomsof
sinusitis (solely fever in 17 out of 22 newly diagnosed
patients) with accompanying radiological findings
(some-timesonlythickeningofthemucosaontheplainfilm),1while
Wonetal.definedsinusitisasradiologicalabnormalitiesof
the paranasal sinuses accompanied by symptom or
symp-toms,suchaspostnasaldrip,rhinorrhea,nasalobstruction,
cough,fever,orheadache.3
Computed tomography scans were analyzed most
fre-quently using a modified version of the method of Lund
andMackay.7,9---11,15,17 Inthismethod20,21 the leftandright
ethmoid,maxillary,frontalandsphenoidsinuseswereeach
givenascorefrom0to2,where0denotedaclearsinus,1
---partialopacity,and2---totalorneartotalopacity,secondary
eithertomucosalthickeningorfluidlevels.Theosteomeatal
complexeswerealsoassignedascore from0 or2,
denot-ingtheir patencyor occlusion.Thereare noclearcutoffs
forcategorizationofCTsinus disease,e.g.inthe workof
Thompsonetal.patientswerearbitrarilydesignatedas
hav-ingno(scoreof0),minimal(1---3),moderate(4---10)orsevere
sinusdisease(11---20),15 whileinthestudyofFulmeretal.
the cutoffs were as follows: nodisease (0), mild disease
(1---6),moderatedisease(7---12)andseveredisease(13---24).9
Adifferentapproachwasusedinstudiesconcerning
pedi-atricpopulation.Thetotalscoreofsinusopacificationwas
divided by the total number of developed sinuses. Based
onthisresult, theseverity of sinusitisonCT was
catego-rized into 4 groups: 0% for no evidence of sinusitis, less
than25%formildsinusitis,26%---50%formoderatesinusitis,
andgreaterthan50% forsevere sinusitis.11,17 Ina workof
Arulrajahetal.usingthe Lund-Mackaysystem,a scoreof
0---3wasappliedforeachsinus,with0fornoopacification,
1for1---49% opacification,2 for50---99% opacification,and
3fortotalopacification,whiletheosteomeatalcomplexes
wereassignedascoreof0and2,denotingtheirpatencyor
occlusionrespectively.17 Other grading systemswere used
eitheralone orin combination withLund systemby other
researchers.Sinusitisusually wasdefinedasthe presence
ofan air-fluidlevel, totaltonear totalopacity ofa sinus
orjustmucosalthickeningaccompaniedbyclinicalsignsof
sinusitis.1,11,15
Interestingly,CTscanisnonspecificinpatientswith
inva-sivefungalrhinosinusitisanddoesnotcorrelatewithsurgical
andpathologicalfindings.Itmayleadtounderestimationof
thediseaseextent,notvisualizingtheextensionofthe
dis-ease beyondthe borders ofthe sinuses. Inthese patients
population, endoscopy and Magnetic Resonance Imaging
(MRI)offerbetterimagingoptions.19,22
In the analyzed studies the endoscopic evaluation of
sinusesdidnotbelongtothestandardmethodsofassessing
the extent of sinus disease. Only Moeller et al. tried to
assess its usefulness in hematological patients.7 Grading
ofsinus diseasewiththeuse ofendoscopywasperformed
accordingthealgorithmofLundandKennedy,whichincludes
thedegreeofpolyposis,edema,scarring,crustingand
dis-charge.Themaximumscoreis10perside.
Theincidenceofsinusitis
The incidenceof sinusitis in adults in the post-transplant
period reached 5---44%,1,3---6 while the incidence of
inva-sivefungal sinusitisinthe cohortofHSCTpatients ranged
between 0.5% and1.7%.16,23 Savageet al.established the
probabilityofdevelopingsinusitiswithin2yearsafterHSCT
at36.9%(95%CI49---77).2
Thetimethatelapsedbeforesinusitisonset,differed
sig-nificantlybetweenpatients.IntheworkofSavageetal.it
ranged between 7 and 1340 days (median 93 days),with
almost 70%of casesoccurring alreadyduringthe first120
days,andonly 10%aftermorethan ayear.2 These results
weresimilartodataofWon andcoworkerswhere median
timetodiagnosisreached4.1months(95%CI1.768---6.432)3
and to the results of Sekine et al., where time to
diag-nosis was 127 days for allogeneic HSCT and 76 days for
autologousHSCT,6whereasintheworkofShibuyaetal.it
rangedbetween2and833days.1InthepaperofKennedy,
who analyzed solely patients with invasive fungal
sinus-itis, symptoms started after an average of 21days, after
HSCT,while diagnosiswasmadeafter25days.23 However,
it must be kept in mind, that patients with symptoms
onset after day +100 were not included into this
analy-sis.The other authors didnotreportthe timetosinusitis
onset.
Riskfactorsofpost-transplantsinusitis
Berlinger et al. in their pioneer study analyzing sinusitis
in immunodeficient and immunosuppressed patients have
found that the White Blood Cells(WBC) count of 2.0G/L
or lessinapatientwithsinusdiseaseandthepresenceof
hematologicmalignancywasaverypoorprognosticfactor.12
In the trialsaddressing strictly hematologic population of
patients,differentparametersweresuggestedaspotential
riskfactorsofdevelopingsinusitisafterHSCT;amongthem
the ones analyzed earlier by Berlinger et al., as well as
primarydiagnosis,diseasestage(completeremissionversus
active/refractory disease), absolute neutrophil count,
low IgG concentration in blood, acute and chronic Graft
versus HostDisease(GvHD),corticosteroiduse,
condition-ing regimen and especially Total Body Irradiation (TBI)
use, bone marrow source --- related vs. unrelated donor,
Cytomegalovirus (CMV) status, concomitant pneumonia,
historyofprevioussinus disease,tobaccouse,asthmaand
Theimpactoftypeoftransplantonsinusitisdevelopment
differedamongstudies.Althoughsinusabnormalitieswere
significantly higher among allografted than autografted
hematopoieticstem celltransplantrecipients(p=0.027),1
no clear association could be made between the type of
transplant and sinusitis. While there was a tendency for
morefrequentsinusitisoccurrenceinthealloHSCTsetting
incomparisontoautologousoneinthestudyofWonetal.
(p=0.06),3 nosuchphenomenon couldbeobservedin the
studyofBentoetal.4
InthegroupofallograftedpatientsonlyhigherTBIdose
(1440or1320cGyvs.1200cGy)wasstatisticallysignificant
fordevelopingsinusitis(p=0.023),whilematchedunrelated
donortransplantordonorCMVseropositivityreachedonlya
borderlinesignificance(p=0.08and0.11respectively).2
TheanalysisoftheimpactofGvHDonthesinusitis
occur-renceyieldedinconsistent results.AccordingtoThompson
etal.,Ortizetal.andBentoetal.itputpatientsathigher
risk of developing sinusitis in the post-transplant period
(RR=4.3; 95% CI 1.7---11; p=0.002),4,15,24 whereas in the
workofShibuyaitdidnothaveanyimpactonmorbidity.1In
thestudyofWonGvHDdidnotinfluencetheoccurrenceof
sinusitisintheentiregroupoftransplantedpatients,
how-ever when asymptomatic patients with solelyradiological
abnormalitiespriortotransplantationwereanalyzed
sepa-rately,bothacuteandchronicGvHDputthesepatientsat
higher risk of developing sinusitis (p=0.005 and p=0.042
respectively).3
Similarly toGvHD, analysis of the impact of
pretrans-plantsinusdisease(symptomsattimeoftransplant,history
of sinusitis, and significant disease on screening CT) on
post-transplant sinusitis led to inconsistent conclusions.
Whileaccordingtosomeauthorsitdidinfluencepost-HSCT
morbidity,3,9---11 accordingtoothersitdidnot.7,15 However,
in the work of Thompson et al. all patients with
abnor-malradiographicfindingsduringscreeningandsymptomsof
sinusitis,aswellasmajorityofpatientswithabnormal
radio-graphicfindingsweretreatedpriortotransplantation.15
Prolonged, profound neutropenia was found in all
patientsexperiencinginvasivefungalsinusitisinthestudyof
Johnsonetal.,16howevernoformalriskfactoranalysiswas
performedbytheauthors.On theotherhandinthestudy
ofSekineetal.,lowerneutrophilcountwasassociatedwith
lowerLund-Mackayscoreatthetimeofrhinosinusitis
diag-nosis,probablyindicatingthatpatientslackingneutrophils
arenotabletomount aneffective inflammatoryresponse
capableofinducingsignificanttomographicabnormalities.6
Itis worthmentioning thattherewasnoincreasedrisk
ofdevelopingsinusitispostHSCTforpatientswithhighrisk
ofdiseaserelapse.
Value
of
sinonasal
evaluation
including
computed
tomography,
endoscopy
and
microbiological
findings
preceding
hematopoietic
stem
cell
transplantation
Sinonasalevaluationwasperformedinthemajorityofcases
withtheuseofpretransplantCT(Fig.2).Intheearlier
stud-iessinusX-rayseriesweretakenasascreeningtest.5Apart
from radiographic methods, also endoscopicand
microbi-Figure 2 CT scan of the sinuses. A polyp obstructing osteomeatalcomplex(whitearrow)inapatientdiagnosedwith acutemyeloidleukemia,qualifiedforallogeneichematopoietic stemcelltransplantation.
ologic findings were included in the assessment of sinus
disease.
Moeller et al. were not able to show any relationship
between the result of pre-HSCT sinonasal evaluation and
post-HSCToutcome.7However,screeningCTwasperformed
onlyfor19outof71analyzedpatients.The averageLund
score prior HSCT was 2.2±3.7, with 79% patients having
score of no more than 3. Mean endoscopic grading,
per-formedforallanalyzedpatients,reached0.6±1.6(77%pts.
---score0;94% pts.---score≤2).Only4outof71patients
(6%),all showing symptoms,were diagnosed withchronic
rhinosinusitis,with3 of them requiring medical
interven-tion.Interestingly,3outofthese4patientshadendoscopic
scoreof0.The authorstherefore concludedthatalthough
endoscopyseemsusefulinevaluationofsinusesingeneral,it
isnotagoodscreeningtoolinpatientsqualifiedforalloHSCT.
In the post-HSCT period only 2 patients developed acute
rhinosinusitis.Therewasnocorrelationwithpretransplant
findings in this group. The authors were also not able to
findanycorrelationbetweenculturesfrommiddlemeatus
andsubsequentsinusitis,asonlyoneoutof33patientswith
culturesdevelopedrhinosinusitis.
Billingsetal.found,analyzingtheextendofsinusdisease
priortotransplantationwiththeuseofscreening CT,that
48%ofpatientshadnosinusdisease,25.9%hadmilddisease,
9.3% moderate disease and 16.7% severe disease. Unlike
otherauthors,theyfoundthatseverityofradiographicsinus
diseaseonpre-HSCT CTscanscorrelatedwithclinicaland
radiographicsinusitislaterinthepost-HSCTcourse,andwas
associated with a trend toward decreased survival.
Two-thirds of patients with severe sinus disease on pre-HSCT
CTscansexperiencedclinicalsinusitisaftertransplantation,
whileonly21.4%ofpatientswithmilddisease.Asmuchas
39.3%ofpatientswithsinusabnormalitiesonpre-HSCTCT
scanshadclinicalsinusitisduringtheirpost-transplantation
course,comparedto23.1%ofthosewithnormalCTscans.10
Inthe most recent study of Zamora et al.,who analyzed
alsothepediatricpopulation,14% ofpatientswithnormal
screeningCTdevelopedpost-transplantsinusitis,compared
with23%withradiographicabnormalitiesand22%with
clin-icalsinusitisalone.Thedifferenceshoweverdidnotreach
statistical significance.Subgroup analysis of patients with
score (mild vs. moderate/severe) was also not found to
correlatewithdevelopmentofclinicalsinusitisafterHSCT
(p=0.58).Thesensitivityofradiographicfindings,analyzed
eitheraloneorincombination,wasloworrangedbetween
19%and56%,whilethespecificityrangedbetween71%and
97%.Thepositivepredictive valueofhavingacuteclinical
sinusitisforagivenradiographicabnormalitywashighestfor
combinedCTfindings(67%),totalsinusopacification(56%),
frothysecretions (53%), and fluid levels(47%) and lowest
formucosalthickeningalone(13%).Inthisstudythe
Lund-Mackay score change of 10 or greater from baseline was
associatedwitha2.8foldincreasedlikelihoodofhaving
clin-icalsinusitis (p<0.001; 95% CI1.32---5.81).11 Kasow etal.
in their study concerning children showed, that as much
as67.2%of alloHSCT and55.4% ofautoHSCT patientshad
abnormalsinusfindings,whichwereunrelatedtothe
under-lyingdiseaseprocesspriortotransplantation.Unfortunately
theauthorsdidnotreportontheseverityofthese
patho-logicalfindings,norontheirimpactonthepost-transplant
outcome.25 Inthestudy ofFulmeretal.meanLundscore
priortotransplantation was3.03, and reached 7.91after
the procedure. However only patients suspected of
rhi-nosinusitis had a CT performed after HSCT. Nevertheless
whenthese patients wereanalyzed separately, there was
asignificantincreaseinLundscoreafterHSCT.Additionally
thesepatientsshowedhigherrateofsinuschangeson
pre-HSCTCTscans.Theauthorsthereforeconcluded,thatthe
pre-HSCTCTscancorrelatedsignificantlytothepost-HSCT
CTscans.9
Won etal. found, that 96 patients (38.1%) out of 252
analyzed,didpresentradiologicalabnormalitiesaloneprior
to transplantation, which translated into sinusitis in 15
of them (15.6%) in the post-transplant period.Among 23
patients(9.1%)diagnosedwithsinusitisbefore
transplanta-tion8hadrecurrentdisease(34.8%).Themagnitudeofthe
radiologicalabnormalitiesisnotreportedinthisstudy;
fur-thermoreallo-andauto-transplantedpatientsarereported
together.3
Indicationsforthetreatmentofsinusitis
Therearenoclearguidelinesfortheoptimalmanagement
ofpatientsdiagnosedtohavesinusitisduringpretransplant
workup,aswellasinthepost-transplantperiod,especially
withrespecttosinussurgery.
Berlingeretal.analyzingsinusitisinimmunodeficientand
immunosuppressedpatientshavefoundthattheWBCcount
of2.0G/Lorlessinapatientwithsinusdiseaseandthe
pres-enceof hematologicmalignancyis a verypoor prognostic
sign and mandates surgical intervention.12 Similar
recom-mendationsweremadebyShawetal.whoadvocatedsinus
surgerypriortoimmunosuppression.26
Other authors recommended a conservative medical
approach to sinusitis in the population of hematopoietic
stem cell transplant recipients,1,27 unless the etiologic
factor is aspergillus, mucormycosis, phycomycetes,
pseu-domonas, which are associated with high mortality
rate,1,16,22especiallyifsphenoidsinusisinvolved.16
Such an attitude may be supported by the results of
Sterman’sanalysis.Heanalyzedtheresultsofsinussurgery
in allogeneic hematopoietic stem cell transplant
recipi-ents, and was not able to show any survival benefit in
patientstreatedaccording toaggressivesurgicalapproach
i.e. antral lavage or ethmoidectomy.28 On the contrary,
patientstreatedsurgicallyhadmortalityrateof57%,which
wasloweredto0%whenendoscopyforpossiblediagnosisof
fungal infectionwasintroduced. Similarly Kennedyetal.,
analyzingsolelypatientswithinvasivefungalsinusitiswere
notabletodemonstrate theadvantageofmore extensive
surgery in comparison to limited drainage procedures or
limiteddebridement.23 Endoscopicsinusectomywasalsoa
valuableoption in patients sufferingfromGvHD,having a
greaterneedforsurgicaltreatment(p<0.001).4
Shibuya et al. advocated that if the sinus disease is
refractorytomedicaltherapy,sinussurgerymaybea
rea-sonableapproach.1
Conclusions
Paranasal sinusitis, asshown in the review, constitutes a
majorproblemforbothhematologiststreatingthepatients
aswellasotorhinolaryngologistsconsultingonsubjects
sus-pected of sinusitis or exhibiting abnormal changes on CT
scans.
Resultsfromquotedstudiesfrequentlyyielded
inconsis-tent results. Furthermore --- many analyses covered both
auto- and allogeneic hematopoietic stem cell
transplan-tations. As shown in the risk factor analysis, patients
undergoingallogeneicSCT areprobablyatotallydifferent
patients’ group than patients undergoingonly autologous
SCT.Thereforethereisaneedforseparateanalysisofthese
groupsof patients.Intheevaluatedstudiesthesignificant
group of the transplanted patients suffered from chronic
myelogenousleukemia(CML), chronicphase.This is nota
standardindicationfortransplantationcurrently,apartfrom
raresituations,whenthereisresistancefortyrosinekinase
inhibitors (e.g.T315Imutation). This patients’ population
differsfromthe‘‘standard’’transplantedpopulationinthe
diseaseduration,numberofpreviouschemotherapycycles
(usuallynone),timespentinthehospital,previoustimewith
neutropeniaandhencethepossibilityofmicrobial
coloniza-tion,especiallywithmulti-drugresistantspecies.
Nevertheless,somerecommendationsfor goodpractice
based upon the current knowledge could be made. First,
althoughdataisinconsistent,itseemsadvisabletoscreen
allpatientsundergoingallogeneichematopoieticstemcell
transplantation with CT prior to procedure. In selected
cases,endoscopyofthesinuses shouldalsobeperformed.
Second, patients with symptoms of sinusitis should be
treated before HSCT, preferably with conservative
medi-cal approach. Third, patients who have undergone HSCT
shouldbemonitoredcloselyfor sinusitis,especiallyinthe
early period after transplantation. We would also like to
stress,thataccordingtosomeauthors,19sinusitismayhave
an occult course, with only persistent fever, which is not
in linewiththe currentlyuseddefinitionorbe less
symp-tomatic than in immunocompetent patients.17 It is safer
for patients to assumethat theyhave sinusitisand
intro-ducetreatment thanneglectthis possibilityandallowfor
bothlocalandgeneralizedspreadofinfectionwhichmaybe
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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