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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?

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.

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

(2)

282

revbrashematolhemoter.2016;38(4):281–282

unusedHSCaddedupto336extrapatientdaysofapheresis

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.

r

e

f

e

r

e

n

c

e

s

1.KumarSK,DispenzieriA,LacyMQ,GertzMA,BuadiFK,Pandey S,etal.Continuedimprovementinsurvivalinmultiple

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.

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