rev bras hematol hemoter. 2016;38(4):281–282
w w w . r b h h . o r g
Revista
Brasileira
de
Hematologia
e
Hemoterapia
Brazilian
Journal
of
Hematology
and
Hemotherapy
Scientific
Comment
Hematopoietic
stem
cell
mobilization
for
autologous
transplantation
in
multiple
myeloma
patients
previously
exposed
to
cyclophosphamide,
thalidomide,
and
dexamethasone:
is
granulocyte-colony
stimulating
factor
alone
enough?
夽
Afonso
Celso
Vigorito
∗UniversidadeEstadualdeCampinas(UNICAMP),Campinas,SãoPaulo,Brazil
Theparadigmformultiplemyeloma(MM)therapyhasevolved
markedlyinthepastdecadewiththeintroductionof
numer-ousnewdrugsandimprovedpatientoutcomes.1
Autologous hematopoietic stem cell transplantation
(aHSCT) iswidely used as part offirst line therapy in the
treatmentoftransplant-eligiblepatientswithMM.2Inthese
patients, hematopoietic stem cell (HSC) mobilization for
aHSCT has commonly been performed using
cyclophos-phamideplusgranulocyte-colonystimulatingfactor(G-CSF)
orG-CSF alone.3,4 However, theinductionregimens should
notincreasethe mobilizationfailurerisk.Thisconcern has
beenespeciallypertinent topatientspreviouslyexposed to
cyclophosphamideorlenalidomideduringinduction,asthese
drugsappeartohamperHSCmobilization.Inthearticlethat
accompaniesthis comment, Crusoeet al. demonstratethe
feasibilityofusingG-CSFalonetomobilizeprogenitorcellsin
MMpatientsinducedwithacyclophosphamide,thalidomide
and dexamethasone regimen.5 The number ofCD34+ cells
mobilizedwas assessedafter using G-CSF withor without
cyclophosphamide.
Theretrospectivestudy ofCrusoeetal.included
eighty-eightMM patientswho underwent aHSCT attwo Brazilian
centers.5 Collectionof>2.0
×106CD34+cells/kg was
consid-eredsufficient. Thegroup that received cyclophosphamide
DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2016.06.004.
夽
SeepaperbyCrusoeetal.inRevBrasHematolHemoter.2016;38(4):302–309.
∗ Correspondenceto:HemocentrodeCampinas,RuaCarlosChagas,480,13083878Campinas,SP,Brazil.
E-mailaddress:afonso@unicamp.br
collected a higher median number of progenitor cells [3.8
(range:3.1–4.4)vs.3.2(range:2.3–3.8)–p-value=0.008].
How-ever,thecyclophosphamideusedinmobilizationdidnotshow
advantagesintermsofmobilization,orimprovedresponseor
survival.
Indeed,wehavetoconsiderthatcyclophosphamideused
formobilizationmayhavesomedisadvantages,suchas
rais-ingthecostoftheprocedureduetohospitalization,higher
tox-icityaspatientstreatedwithcyclophosphamiderequiremore
timeforengraftmentofplateletsandneutrophils,and
poten-tiallyahigherincidenceofpost-transplantinfections.
Elimi-natingcyclophosphamidefromthemobilizationregimenhas
improvedpatientconvenienceandhasdecreasedtheduration
ofmobilizationtreatmentbyapproximatelyninedays.6
Wemightalsoarguethatthehighernumberof
progeni-torcellscollectedwithcyclophosphamideplusG-CSFwould
enablethestorageofmoreHSCforasecondsalvage
trans-plant. However,theutilization ofstored autologousHSCto
supportasecondaHSCTinMMpatientsintheeraofnovel
agenttherapieshasbeenaddressed.DatafromSeattleshowed
thatof726patientswhohadresidualHSCinstorageaftertheir
first aHSCT,only135patientsunderwentasecond aHSCT.7
The percentage of patients receiving a second aHSCT has
declinedovertime.Theresourcesrequiredtocollectandstore
http://dx.doi.org/10.1016/j.bjhh.2016.07.006
1516-8484/©2016Associac¸ ˜aoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Thisisan
282
revbrashematolhemoter.2016;38(4):281–282unusedHSCaddedupto336extrapatientdaysofapheresis
and41,587extrapatientmonthsofcryopreservation,
trans-lating into a higher average cost per patient. The authors
concludedthatareconsiderationofconventionalHSC
collec-tionandstoragepracticeswouldsavesignificantcostforthe
majorityofMMpatientswhoneverundergoasecondaHSCT.6
WedonotknowwhethertheresultsfromSeattlemightbe
translatedtotherealityofBrazilianpatientstreatedwithin
theBrazilianNationalHealthSystem(SUS)that,insome
cen-ters,precludestheuseofnovelandmoreeffectiveagentsthat
wouldleadtobetterresponsesbeforeandafteraHSCT.
Inconclusion,thestudybyCrusoeetal.showedthat
suffi-cientprogenitorcellscanbemobilizedtoperformatleastone
aHSCTwiththeuseofG-CSFaloneinpatientsinducedusing
thecyclophosphamide,thalidomideanddexamethasone
pro-tocol.Thisstrengthensthecurrentstudyasitmakesa
valu-ablejudgmentregardingthelimitationsofperformingaHSCT
inBrazilandtheneedtocutcosts.Thequestionsaddressed
herewillhaveapracticalimpactontheclinicalpractice.
Conflicts
of
interest
Theauthordeclaresnoconflictsofinterest.
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myeloma:changesinearlymortalityandoutcomesinolder patients.Leukemia.2014;28:1122–8.
2.ShahN,CallanderN,GangulyS,GulZ,HamadaniM,CostaL, etal.Hematopoieticstemcelltransplantationformultiple myeloma:guidelinesfromtheAmericansocietyforbloodand marrowtransplantation.BiolBloodMarrowTransplant. 2015;21:1155–66.
3.GiraltS,StadtmauerEA,HarousseauJL,PalumboA,Bensinger W,ComenzoRL,etal.Internationalmyelomaworkinggroup (IMWG)consensusstatementandguidelinesregardingthe currentstatusofstemcellcollectionandhigh-dosetherapyfor multiplemyelomaandtheroleofplerixafor(AMD3100). Leukemia.2009;23:1904–12.
4.BensingerW,DiPersioJF,McCartyJM.Improvingstemcell mobilizationstrategies:futuredirections.BoneMarrow Transplant.2009;43:181–95.
5.CrusoeEQ,HigashiF,MartinezGA,BarrosJC,BellessoM, RossatoM,etal.Isitfeasibletousegranulocyte-colony stimulatingfactoralonetomobilizeprogenitorcellsin multiplemyelomapatientsinducedwithacyclophosphamide, thalidomideanddexamethasoneregimen?RevBrasHematol Hemoter.2016;38.
6.GertzMA,KumarSK,LacyMQ,DispenzieriA,HaymanSR, BuadiFK,etal.Comparisonofhigh-doseCYandgrowthfactor withgrowthfactoraloneformobilizationofstemcellsfor transplantationinpatientswithmultiplemyeloma.Bone MarrowTransplant.2009;43:619–25.