rev bras hematol hemoter. 2016;38(4):358–360
w w w . r b h h . o r g
Revista
Brasileira
de
Hematologia
e
Hemoterapia
Brazilian
Journal
of
Hematology
and
Hemotherapy
Case
report
A
clinical
challenge:
Treatment
of
acute
myeloid
leukemia
in
a
Jehovah’s
Witness
Daniela
Cárdenas-Araujo
∗,
Elías
Eugenio
González-López,
Xitlaly
Judith
González-Leal,
José
Carlos
Jaime-Pérez,
David
Gómez-Almaguer
UniversidadAutónomadeNuevoLeón,HospitalUniversitario,Monterrey,Mexico
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Articlehistory:
Received4February2016 Accepted12May2016 Availableonline4June2016
Introduction
TheJehovah’sWitnessreligiousmovementisaChristiansect with over 2.6 million followersworldwide that forbids the transfusionofbloodandbloodcomponentstoitsmembers.1
There is limited experience in the treatment of Jehovah’s Witnesseswithacutemyeloidleukemia(AML).Treatmentof patients,whodonotacceptrequiredbloodsupporton reli-giousgrounds,isalwaysadifficultproblem.Thisdilemmais ofparticularconcernincasessuchasacuteleukemiainwhich thephysicianhimself,bychoosingandapplyingappropriate treatment,mayincreasetheneedfortransfusionsupport.2
The standard treatment for AML is seven days of an anthracyclineand threedaysofcytarabine (7+3);withthis regimen70–80%ofyoungadultsand40–60%ofolderadults, willachievecompleteremission.3Thecombinationof
cytara-bine plus an anthracycline results in severe pancytopenia andthereforerequirestransfusionsupport.4Duringinduction
chemotherapy,patientsaregivenanaverageof10.8unitsof redbloodcellconcentratesand8.5platelettransfusionsover aperiodofabout30days.5
∗ Correspondingautorat:HospitalUniversitario,UniversidadAutónomadeNuevoLeón,Av.MaderoyGonzalitos,Col.MitrasCentro,
Monterrey,CP.64460,Mexico.Tel.:+5218183338111.
E-mailaddress:dra.danielacardenas@hotmail.com(D.Cárdenas-Araujo).
Corsettietal.describedachemotherapyregimendesigned forelderlyAMLpatientsthathadlowhematologicaltoxicity, andresponseratesof36%.6Inthissetting,anotherdrug,
aza-cytidineisusedtotreatAMLinelderlyorfragilepatientswho arenotcandidatesforanintensivechemotherapyregimen.7
However,sinceazacytidinewasnotavailableatourinstitution duetofinancialrestrictions,weadministeredacombination oflow-dosecytarabineplusvalproicacidtoourpatientafter sherejectedstandardAMLtherapy.
Case
report
InJune2014,a35-year-oldfemaleJehovah’sWitnesspresented weakness,fatigue,malaiseandskinlesionsofonemonth’s duration.Peripheralbloodwastestedandhercompleteblood count(CBC)gaveahemoglobin(Hb)levelof8.6g/dL,an ele-vatedwhitebloodcellcount(WBC)of30×109/Landaplatelet
countof71×109/L.
Uponphysicalexaminationoftheskin,painless,nodular andviolaceouslesionsdisseminatedontheface,neck,trunk andextremitieswereidentifiedasmyeloidsarcomas.Shealso
http://dx.doi.org/10.1016/j.bjhh.2016.05.003
revbrashematolhemoter.2016;38(4):358–360
359
presentedwithswollenandspongygumsandasoftpainful andtendertissuetumorontherightsideoftheneckwitha meandiameterof6cm.
Abonemarrowaspirationrevealed ahypercellular mar-row with 70% monoblasts. Flow cytometrywas performed revealinganaberrant immunophenotype consistingoftwo populationsofblasts:the firstwasHLA-DR+, CD13+, CD33+
weak,CD34+,CD45+weak,CD64+,CD117+,MPO+in50%,and
the second population included 13% of the blasts with a HLA-DR+,CD33+,CD34+weak,CD45+,CD56+,CD64+,CD123+,
MPOc+ phenotype. Cytogeneticand molecularstudies were
notperformed.ShewasdiagnosedwithAMLnototherwise specified using the World Health Organization Classifica-tion. Biopsies of the skin and the soft tissue tumor were performedshowinganinfiltrateofmonocytoidcells(MPO+,
CD68+,CD34+,CD117+),whichwasconsistentwithleukemia
cutis.
Thepatientandfamilywereinformedthattheappropriate treatment(7+3) implied markedand prolonged myelosup-pression requiring transfusion support, and the patient refusedtograntconsentfortransfusions.Aminimally myelo-suppressivetreatmentplanconsistingonlyofvinblastinefor cytoreductionwasthenproposedandaccepted.Thepatient was fully aware of the reduced probability of achieving a durablecompleteremission.
She was hospitalized at diagnosis and 10mg of vin-blastinewas administered forcytoreduction. Thenext day the WBCcount was 17.4×109/L. Four days later, the WBC
was4.5×109/L,Hb was7.7g/dLand theplateletcountwas
39×109/L.
Aweeklater,shecomplainedaboutprogressive dyspha-giaandanincreaseinthemyeloidsarcomastoabout10cm. HerCBCrevealedWBC15×109/L,Hb8g/dLandplateletcount
100×109/L.Shereceived17mgmitoxantroneand
intermedi-atedoseofAra-C(twodosesof1.5gIVb.i.d.).Thenextday boththedysphagiaandtumormassdisappeared.Treatment wasuneventful,withneitherinfectiousnorhemorrhagic com-plications,however on Day +12 shepresented withsevere pancytopenia[Hb:6g/dL,absoluteneutrophilcount(ANC):0, plateletcount:30×109/L],thereforewedecidedtochangethe
treatmentregimenandlowdoseAra-Candvalproicacidwere giveninanoutpatientsetting.
A month later (Day +26) her CBC revealed Hb 9.1g/dL, WBC4.05×109/L,ANC0,andplateletcount130×109/L.She
receivedAra-C(20mgb.i.d.)asasubcutaneousinjectionfor fourdays,subsequentcoursesoflowdoseAra-Cwereplanned afteratleast21days,withvalproicacidstartingat5mg/kg
daily divided in two equal doses. Dose escalation of val-proicacidwascarriedoutaccordingtopatienttoleranceuntil theplasmatherapeuticrange(50–100mcg/mL)wasreached.
ThispatientalsoreceivedprophylacticantibioticsiftheANC droppedbelow0.5×109/L.Shereceivedlevofloxacin(500mg
POeveryday),acyclovir(400mgb.i.d.)anditraconazole(100mg daily). The patient refused erythropoietin due to religious beliefs.Inevery cycleonemoreday ofAra-Cwas addedif theHbwas>7g/dLandplateletcount>30×109/L.Duringthe
sixth courseshereceivedsevendaysofAra-C,afterwhich severe cytopenias developed; it was decided toreduce the Ara-Ctosixdaysinthenextcourse.Intheeighthcycle,she presentedwithhyperleukocytosis(176×109/L)andthesizeof
themyeloidsarcomasincreased.Atthattime,10mgof vin-blastine were againadministered, and cytoreduction (WBC 3.05×109/L)withANC0wasobtained,alongwithreduction
inthesizeofthesarcomas.
Shereceivedeightcoursesoftreatmentwithout transfu-sionsorinfectiouscomplicationsvisitingtheoutpatientclinic foracheckuptwiceaweek;duringthistime,shewasableto performherbasicdailyactivities,socialandreligious.
Afterthelastcourseoftherapy,shepresentedacoughwith expectorationbutwasafebrile.AchestX-rayrevealed bilat-eralperipheralpulmonaryinfiltratesconsistentwithbilateral pneumoniaofunknownetiology.Sherefusedtobe hospital-izedandwasmanagedwithantibioticsathome.Thepatient diedeightmonthsafterdiagnosis.
Discussion
There isonly onereportofsuccessful remissioninduction using standardchemotherapy(7+3)inaJehovah’sWitness with AML.8 In another report, a 20-year-old woman was
diagnosed with AML by morphology in 1979, but without molecular,cytogeneticsorflowcytometryconfirmatory stud-ies.Shewastreatedwithvincristine,prednisoneandAra-C and was cured atthe time ofthe report.9 On the grounds
of having only a morphology diagnosis and the patient respondedtothatspecifictreatment,wehypothesizethatthis casemayhavebeenalymphoblasticleukemia.Thereareother casereports onpatients survivinglongerthan our patient, howeverallweretreatedinaninpatientsetting,and/orhad infectiouscomplications.10
Weacknowledgethatazacitidineisatherapeuticoptionfor patientswithmyelodysplasticsyndromesandolderpatients withAML.11ItsuseinaJehovah’sWitnesshasbeenreported,
howeverbecauseofitselevatedcostsitwasnotavalidoption forthispatient.
HereinwereportourexperiencetreatingaJehovah’s Wit-ness using vinblastine, low dose Ara-C and valproic acid but without blood transfusions, based on a treatment for elderly patients published byCorsetti et al.6 who reported
anoverallresponserateof35%andanoverallmedian sur-vivalofeightmonths(range: 2–36).These authorsincluded histonedeacetylaseinhibitors,suchasvalproicacid,which haveaprovenefficienttoovercomedifferentiationarrestof AML blasts.12 We decided to use this regimen because of
itsresponserates.LowdoseAra-Chasbeenusedinseveral regimens ofphaseIItrialsforAMLforseveralyearsgiving responsesthatincludecompleteresponse.13Thistherapyis
welltoleratedandcanbegiveninanoutpatientorhomecare setting.
Vinblastine is a drug rarely used in the treatment of AML.Vincaalkaloids,suchasvinblastine,targetmicrotubule dynamicsbybindingtotubulinmonomersanddimers.14They
havebeenusedinrelapseorrefractoryAMLpatients.There are somestudies usingvinblastine incombination therapy withAra-C,VP16-213(etoposide)andvincristineforrelapsed AML.15Thedrughasbeenusedasmonotherapyinchildren
withAML,withareportedremissionrateof53%.16
360
revbrashematolhemoter.2016;38(4):358–360vinblastine,witha77%responserateofpatientswithinthe firstweeksoftreatment.Thus,vinblastineisalesscostlyand lesstoxicoptionforpalliativecytoreduction.17Ourpatient
ini-tiallyreceivedvinblastinealone,butaweeklater,themass reappeared.Soweconcludedthatvinblastinecanbeusedat thestartofthetreatmenttodecreasetumorburdeninLMA, butitshouldbefollowedbysupplementarytherapy.Wedid notknowwhethervinblastinewouldleadtoadditional trans-fusionrequirements,butintheexperienceofourservice,it isasafedrugtoreduceoreliminatethenecessityofblood transfusionsinelderlypeopleorinpalliativecaretreatment.
Conclusion
WeadministeredacombinationofAra-Candvalproicacidin ourAMLpatient,togetherwithvinblastinewhentherewas ahightumorburden.Thisregimenwaswelltolerated,with goodresponseandregressionofextramedullaryinfiltration. Thepatientsurvivedforeightmonthswithouttransfusions or infectiouscomplications, and shewashospitalized only atdiagnosis receivingthe rest ofthe therapyasan outpa-tient.Thealternativetreatmentdescribedappearstobeavalid optionthatoffersanacceptablequalityoflifeforAMLpatients refusingstandardtreatmentthatincludestransfusionsand hospitalization.
Conflict
of
interest
Theauthorsdeclarenoconflictsofinterest.
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1. BrownNM,KeckG,FordPA.Acutemyeloidleukemiain JehovahWitnesses.LeukLymphoma.2008;49(4):817–20.
2. BoggsDR.Jehovah’switnesseswithleukemia.HospPract(Off Ed).1985;20(3):92,94-5,98passim.
3. DöhnerH,EsteyEH,AmadoriS,AppelbaumFR,BüchnerT, BurnettAK,etal.Diagnosisandmanagementofacute myeloidleukemiainadults:recommendationsfroman internationalexpertpanel,onbehalfoftheEuropean LeukemiaNet.Blood.2010;115(3):453–7.
4. OhtakeS,MiyawakiS,FujitaH,KiyoiH,ShinagawaK,UsuiN, etal.Randomizedstudyofinductiontherapycomparing standard-doseidarubicinwithhigh-dosedaunorubicinin
adultpatientswithpreviouslyuntreatedacutemyeloid leukemia:theJALSGAML201Study.Blood.
2011;117(8):2358–65.
5.JansenAJ,CaljouwMA,HopWC,vanRhenenDJSM. Feasibilityofarestrictivered-celltransfusionpolicyfor patientswithintensivechemotherapyforacutemyeloid leukaemia.TransfusMed.2004;14(1):33–8.
6.CorsettiMT,SalviF,PerticoneS,BaraldiA,DePaoliL,GattoS, etal.Hematologicimprovementandresponseinelderly AML/RAEBpatientstreatedwithvalproicacidandlow-dose Ara-C.LeukRes.2011;35(8):991–7.
7.CogleCR,ScottBL,BoydT,Garcia-ManeroG.OralAzacitidine (CC-486)forthetreatmentofmyelodysplasticsyndromesand acutemyeloidleukemia.Oncologist.2015;20(12):1404–12.
8.GoldbergSL,ChanCS,DawkinsFW,MehlmanTW,Schechter GP.ShouldJehova’switnessesbedeniedintensive
chemotherapyforacuteleukemia?NEnglJMed. 1990;322(11):777–8.
9.BrocciaG.Long-termcontinuouscompleteremissionofacute myeloidleukemiainaJehova’switnesstreatedwithoutblood support.Haematologica.1994;79(2):180–1.
10.GareliusH,GrundS,StockelbergD.Inductionwith azacytidinefollowedbyallogeneichematopoieticstemcell transplantationinaJehovah’sWitnesswithacutemonocytic leukemia.ClinCaseRep.2015;3(5):287–90.
11.YamamotoY,KawashimaA,KashiwagiE,OgataK.Casereport aJehovah’switnesswithacutemyeloidleukemiasuccessfully treatedwithanepigeneticdrug,azacitidine:acluefor developmentofAnti-AMLtherapyrequiringminimumblood transfusions.CaseRepHematol.2014;2014:141260.
12.LeydenM,ManoharanA,BoydA,ChengZM,SullivanJ.Low dosecytosinearabinoside:partialremissionofacutemyeloid leukaemiawithoutevidenceofdifferentiationinduction.BrJ Haematol.1984;57(2):301–7.
13.BaccaraniM,TuraS.Differentiationofmyeloidleukaemic cells:newpossibilitiesfortherapy.BrJHaematol. 1979;42(3):485–7.
14.DhamodharanR,JordanMA,ThrowerD,WilsonL,
WadsworthP.Vinblastinesuppressesdynamicsofindividual microtubulesinlivinginterphasecells.MolBiolCell. 1995;6(9):1215–29.
15.SauterC,FehrJ,FrickP,GmuerJ,HoneggerH,MartzG.Acute myelogenousleukemia:successfultreatmentofrelapsewith cytosinearabinoside,VP16-213,vincristineandvinblastine (A-triple-V).EurJCancerClinOncol.1982;18(8):733–7.
16.GeiserCF,MitusJW.Acutemonocyticleukemiainchildren anditsresponsetovinblastine(NSC-49842).Cancer ChemotherRep.1975;59:385–8.
