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CASESTUDY:ACUTEMYELOIDLEUKEMIA

CaseStudy:AcuteMyeloidLeukemia
NicoleMischler
ArgosyUniversity

CASESTUDY:ACUTEMYELOIDLEUKEMIA

Introduction

Forabouttwoweeks,Iwasfortunateenoughtopartakeinthetotalbody
irradiationofapatientdiagnosedwithacutemyeloidleukemia.ThepatientwhomI
wasabletodothisstudyonwasNarcellaGonzalaz.DuringNarcellastwoweek
journeywithourradiationtherapydepartmentIwasabletoobserveandparticipateinthe
simulationandtreatmenttotreatandconditionherhematopoieticsystemforherbone
marrowtransplant.FrommyexperiencewithNarcellasjourney,Iwillpresentacasestudy,
fromconsulttofollowup,aswellasprovidefurtherinformationofacutemyeloid
leukemia.

Consultation

OnthemorningofOct.14,2015Narcellaheadedovertotheradiationoncology
facilityfromherprimaryhospitalnextdoor.By9:30a.m.Iwaspleasedtobeacquainted
witha22yearoldfemalewhoseemedveryfamiliarwithherleukemia.Soonafterarrival
theoncologynurseconductedanassessment.Narcellasvitalssignsyieldedatympanic
temperatureof98.5degreesFahrenheit,abloodpressureof111/63,aheartrateof92
beatsperminute,17respirationsperminuteandshewasnotexperiencinganylevelof
pain.
Narcellajustrecentlygraduatedcollegeandcurrentlyliveswithherparents.

CASESTUDY:ACUTEMYELOIDLEUKEMIA

Althoughshejustrecentlybeganoccasionallysmokingcigaretteswithinthepastyear,
shesneversmokedthembefore.Hergrandmotherhadbreastcancerandalsohadan
unclediagnosedwithbraincancer.InOctober2003Narcellawasdiagnosedwithacute
myeloidleukemia.Afteraroundofchemotherapyandamatchedsiblingbonemarrow
transplant,shesbeenhealthysincethen.
InlateAugustof2015Narcellawasinvolvedinamotorvehicleaccidentand
sufferedtraumaandbruising.Acompletebloodcountwasperformedonhersinceshe
alsoexperiencedpharyngitis.Thetestyielded2.3trillion/LWBCs,8.3grams/dLof
hemoglobinand140,000mcL.Arepeatcountwasperformedalongwithabonemarrow
exam.Theresultsportrayedacircumstanceof75%myeloblastsandaconditionof
pancytopenia.
Subsequentofamotorvehicleaccident,Narcellawasabletodiscoverthatshewas
sufferingfromeasybruising,acutepharyngitis,withperipheralblastscellsonherblood
smear.Withabonemarrowaspirate,itwasconfirmedthatherAMLhasrelapsed.Based
ontheFrenchAmericanBritish(FAB)classificationsystemofAML,herLeukemiais
classifiedasanM2subtypewhichentailsacutemyeloblasticleukemiawithmaturation.
Soonafter,anunrelatedbonemarrowdonorwasidentifiedforNarcella.

Simulation

Afterherconsultationsheprecededtotheradiationoncologydepartmentforthe
simulationofhertotalbodyirradiation.Thefirststeprequiredhertolaysupineonthe

CASESTUDY:ACUTEMYELOIDLEUKEMIA

TBItableontwovacfixbags.Awholebodymoldwasthenbuiltupandencompassed
aroundherforimmobilizationandreproducibility.Onceherpositioningwassatisfactory,
bodythicknessesmeasurementwereobtainedthroughoutdifferentpointsofherbody.
Thesemeasurementswerethenusedtocreatetissuecompensatorstoevenout
transmissionacrossthebeambasedonhervaryingbodythicknesses.Narcellawasthen
strappedintothevacfixesandtablewithseatbelts.Thetablewastiltedinamannerwhere
herbodyfacedtowardsthegantryhead,whichallowedthebeamtobeenfacewithNarcella
andthedivergencetocaptureherentirebody.Atthispointshewassuspendedalmost
horizontallyonourTBITable.Acontourofherbodywastracedonatemplatebythe
dosimetrist,basedonhersilhouette,usingthefieldlightofthegantry.Thisbodycontour
servesasaguideduringtreatmentplanningsothedosimetristcanreferenceplacementof
tissuecompensatorsaswellaslungblocks.
Afteraboutanhourofsimulationthepositioningpreparationfortheanteriortoposterior
positioningwascomplete.Shewasthenplacedlayingproneonanothersetofvacfixesand
simulationwasperformedinasimilarcourseastheanteriortoposteriorposition.Simulation
wasfulfilledwithintwohours.Finally,aCTscanofherthoraxwasobtainedtodetermine
lungdepthforherlungblocks.Aculminationofallthemeasurementscomposedhertreatment
plan,lungblocksandtwosetsoftissuecompensatorsforNarcella.
TwodayslateronOct.16Narcellareturnedtotheradiationoncologydepartment.
Wesituatedthepatientintoherbodymoldsandarrangedfortheanteriorposteriorfield.
AbeamspoilerwasplacedbetweenNarcellaandthebeam.Thelungblockswereplacedon
thebeamspoilerandxrayfilmsweretakentodeterminecorrectplacementofthelung

CASESTUDY:ACUTEMYELOIDLEUKEMIA

blocks.Followingaboutsixattemptsoflungblockplacementandimaging,theblocks
wereaccuratelyshieldingthelungandfilmapprovalwasgrantedfromthephysician.We
thenaccomplishedthesimilarprocessforherposteriortoanteriorfieldandtheblocks
weremarkedonherchest.Narcellawasreadyfortreatment.

DailyTreatment

PriortoLuigisinitialvisittoradiationoncology,shecompletedaroundofchemotherapy.
TheinductionchemocomprisedaprotocolofclofarabineandAraC,whichoccurredonOct.
10throughOct.18.IntermsofherTBI,herplanentailedtwoAPandPAfields,with40cm
x40cmfieldsized,gantryanglesof259degrees,at60MUswiththewholefield
encompassingherwholebody.Eachfieldrequiredabidailyapproach,treatmentinthe
morningandintheafternoonat6hourintervals.
Ontreatmentday,Oct.21st,Narcellaunderwenttotalbodyirradiationat8a.m.twofractions
fromAPandtwofractionsfromPAweredelivered.Shethenreturnedat2p.m.fortwo
morefractionsfromAPandPAforatotalof165cGy.Thiscontinuedonforthenext3days
atthesameexacttimes,totalingacumulativedoseof1320cGy,ateightfractionsof165cGy
perday,withaphotonenergyof6MeV.
UponcompletionofherTBI,Narcellasnauseawasmorepersistentwhichwasimprovedwith
Aloxi,anantiemetic.Increasedfatiguealsosetinfurthermorewithfeversandchills.
Besidesthenausea,Narcellatoleratedhertotalbodyirradiationwell.
ThefollowingSunday,soonafterherTBI,NarcellaunderwentaroundofCytonxanandAnti

CASESTUDY:ACUTEMYELOIDLEUKEMIA

thymocyteGlobulin(ATG).Thistreatsthesystemforthecancer,aplasticanemia,and
conditionshersystemforpreventionofgraftversushostdisease.Finally,herbonemarrow
transplantfromamatchedunrelateddonorwasintitializedontheThursdayafter.

Followup

Regardlessofawellpreparedhemopoieticsystem,itisnotalwaysanassuranceathatpatients
bodywilleluderejectionofthenewstemcells.AccordingtoNarcellasstatusinearlyDecember,
shehasbeensufferingfromacutegradeIIgraftversushostdisease.Pathologicfindingsinsist
thenewlytransplanteddonorcellshavecausedorganrejectioninthestomach,UGIandcolon,
whichhavebeenmanagedthebysteroids,TacrolimusandCellcept.Shehasalsobeenenduring
analteredmentalstatusandshorttermmemorylossleadingtoepisodesofanxiety,thathave
improvedrecently.Narcoticshavebeeneasingchronicpain.AsofDec16Narcellasbloodcounts
remainconsistentlyexceptionalandnonewlesionsexist.

AcuteMyeloidLeukemia

Acutemyeloidleukemiaisacancerthatoriginatesinthebloodandbonemarrow.Itisthemost
commonformofacuteleukemiainadults.Whenthebonemarrowroutinelyproducesstem
cellsforblood,itmaybemyeloidorlymphoidstemcells.Whichareinitiallyimmatureand
becomematureandhealthywithtime.IncidentofAMLhaltsthematuringprocessofthestem
cellsandinsteadtheyformintoimmaturemyeloblastsormyeloidblasts.Theseabnormalcells

CASESTUDY:ACUTEMYELOIDLEUKEMIA

infiltratethebonemarrow,blood,spleenandliver.(NationalCancerInstitie,2014)

Etiologyandepidemiology

Ingeneral,malesareatagreaterriskforthedisease.OtherAMLriskfactorsincludeblood
andgeneticdisorders.Blooddisorderssuchaschronicmyeloproliferativedisorderand
myelodyspasticsyndromecandevelopAML.Problemscausedbytheseconditionsinclude
lowbloodcellcountsandirregularcellscirculationinthebonemarrowandblood.These
disordersmayeventuallyadvanceintoAML.(AmericanCancerSociety,2014)Genetic
disordersthatmaycontributetoAMLincludeataxia,neurofibromatosis,Schwachmansyndrome,
DownSyndrome,andseverecongenitalneutropenia.Thesearejustaselectfewbutthemajority
ofgeneticinstancesdonothaveaconcreterelationtoAMLalthoughindividualswithimmediate
familymembersthathavebeendiagnosedwithAMLareatagreaterrisk,especiallyifthatfamily
memberisanidenticaltwinthatisyoungerthan1yearold.(AmericanCancerSociety,2014)
CertaincancertreatmentsalsoescalatethepossibilityofAML,chemotherapyandradiotherapy
regimenstobespecific.Alkylatingandplatinumagentsarethetwofocuschemotherapeutic
agents,especially8yearssubsequenttotreatment.Radiationexposuretoafetusisapproached
withcautionasitcanstimulatearisk.Althoughtheknownextentoftheriskfromradiationis
faint,itisnottakenlightlyintheprofession,especiallyiftheexposuretothefetusiswithinthe
firstmonthsofgrowth.Japaneseatomicbombsurvivorswerealsoburdenedwithagreaterrisk,
sincetheeventproducedahighdoseradiationexposure.Thispeakedat6to8yearsafterthe
exposure(AmericanCancerSociety,2014).

CASESTUDY:ACUTEMYELOIDLEUKEMIA

SmokingistheonlyconfirmedinducedcarcinogenicriskfactorforAML.Manytimestobacco
isassociatedwithcancersofthelarynx,mouth,throat,andlungsbutthecancercausingagents
intobaccoarecaptivatedbythelungsandtransportedviathebloodstreamthusdirectlyaffecting
theblood.AnotherchemicalthatposesasariskofAMLisbenzenewhichisasolventutilized
inrubber,oilrefineries,shoesmanufacturing,glues,cleaningproductsanddetergentsjusttoname
afew.ExposuretoformaldehydemayalsoinfluentAML.(AmericanCancersociety,2014)

Diagnostics

Uponconsultationwithadoctor,questionswillbeaskedpertainingtolinkstothesechemicals.
Exposuretoanyofthesechemicalsmaybefoundinthemedicalhistoryandphysicalexamthe
doctorwillperform.Attentiontotheeyes,mouth,spleen,liver,lymphnodesandnervous
systemisfundamentalfortheexaminationsastheseareasofthebodymayunveilsymptoms
triggeredbyabnormalbloodcells.Symptomssuchasanemia,infections,bruisingorbleeding
willcallforfurtherbloodcountstoestablishadiagnosisofleukemia.(American
CancerSociety,2013)
Thecompletebloodcountsexaminethedifferentialsinthenumberofdifferenttypesofwhite
bloodcells.Peripheralbloodsmearsarealsoperformed.Thistestfocusesonthevolumeof
cellscirculationinthebloodaswellastheirappearance.AMLpatientscontainmyeloblasts
andlackredbloodcellsandplatelets.
Followingthebloodwork,bonemarrowsamplesareobtained.Mostsamplesareharvested

CASESTUDY:ACUTEMYELOIDLEUKEMIA

fromtheposteriorpelvicbone,whichinvolvetwotypesofsamples,abiopsy,andanaspiration.
Bothareaccomplishedsimultaneously.Doctorsrequire,bothbloodcountsandbonemarrow
resultstoreassureadiagnosis.
AdditionallabworkthathelpsaidthediagnosesofAMLiscomprisedofSpinalfluidsamples,
cytochemistry,flowcytometryandimmunohistochemistry,cytogenetics,Fluorescentinsitu
hybridization(FiSH)andPolymerasechainreaction(PCR).IfAMLissuspectedtoinfiltrate
theCNSsystemalumbarpunctureorspinaltapisdonetocheckforthespreadofthedisease
andchemotherapyagentsareinsertedifneedbe.Thismayalsopreventspreadintothebrain.
Cytochemistryisattainedwithchemicaldyesthatmicroscopicallyrevealleukemiccells.
Antibodiesareexposedtothecellsduringflowcytochemistryandimmunohistochemistry,
whichfastentocertainleukemiacells.ThistestdistinguishesbetweendifferentAMLcells,
aprocesscalledimmunophenotyping.StudyingDNAstrainsisusefulforcytogenetics.AML
displayscertainchangesinthechromosomesandcytogenetictestsmayfactorinanAML
diagnose,dependingonthechromosomevariations.Inadditiontocytogenesis,fluorescent
insituhybridizationorFISHincorporatefluorescentdyesthatadheretogenesexposing
changesinthechromosomes.Thiscanpickupdeviationscytogeneticscannotdetect.
Sinceleukemiadoesnotproduceperceptibletumors,imagingstudiesarenotutilizedfor
diagnosingAML.Instead,imagingisemployedtoconfirminfectionsandfurthercomplications
initiatedbyAML.(AmericanCancerSociety,2013).Xrayimagesaresuitedforfinding
infectionsinthelungsandCTscanscanshowenlargedlymphnodesandorganssuchasthe
spleen.CTimagingmaybeexecutedincombinationwithcontrastorPETimaging.
Ultrasoundscanalsoverifyenlargedorgans.

CASESTUDY:ACUTEMYELOIDLEUKEMIA

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Pathology

Althoughtheseimagingstudiesmaycontributealottothediagnoses,itdoesnotsuffice
AMLwithoutthehematopoieticresults.Aspreviouslystatedthedevelopmentofthedisease
isinitiatedwithmyeloidstemcells.Thefinalproductofthesestemcellsmayeithermature
intooxygencarryingredbloodcells,infectionfightingwhitebloodcells,orbloodclotting
platelets.Duetotheleukemicnaturethestemcellstransitionintoimmaturewhiteblood
celltermedmyeloblasts.MyeloblastsareirregularanddonotmatureintoahealthyWBC
duetochromosomaltranslocationsandgeneticdefects.Constructionofregularwhite
bloodcellsilldecline:quickproliferationofthemyeloblastswilloccuralongwithareduced
capacityofapoptosis.Overpopulationofmyeloblastsovercomesthematureredbloodcells,
whitebloodcells,andplateletsresultingininfections,anemia,andabnormalbleeding.
(SeiterK,2014)

TreatmentOptions

Afteradiagnosisisformulatedtreatmentneedstobeinitiatedassoonaspossible.The
intentofradiotherapyfortreatingAMListodestroythebonemarrowandtheleukemic
cellspriortoabonemarrowtransplantbymethodoftotalbodyirradiation.AftertheTBI,
thenewdonorstemcellsorthepatientsownbloodthatwaspreviouslyharvested
(autologoustransplant),isadministeredtothebloodstreaminhopesthatthestemcellswill

CASESTUDY:ACUTEMYELOIDLEUKEMIA

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regeneratehealthynewblood.Totalbodyirradiationregimesareadministeredtwiceaday
for3to4daysortheradiationcanbedeliveredasasingledose.Eachtreatmentis
accomplishedbyadministeringtheradiationtoonesideofthebodyfor10to15minutes.
Theoppositesideofthebodyistreatedinthesamemanner(CancerResearchUK,2014)
IFthediseasehasspreadtotheCNSsystem,furtherradiotherapytreatmentisadministered
forwholebrainandspinalcord.
TreatmentforthediseasedependsonwhattypeofAMLthepatienthas.Bonemarrow
transplantsareusedinconjunctionwithhighdosesofchemotherapybutradiationisnot
alwayscertain.Itispossiblethepatientmayundergoallthreetreatmentmodalitiesorif
thepatientisnotacandidateforhighdoeschemotherapy,lowerendurabledosesofchemo
andradiationisgivenwithaminitransplant.(WebMD,2013)
ThewholeroutineoftreatingAMLconsistsoftwoportions,inductiontherapyand
consolidationtherapy.InductiontherapyentailskillingasmanyAMLcellsasachievable.
Regainingnormalbloodcountsanddiminishingthesignsofthedisease.Themainpurpose
ofinductiontherapyistoaccomplishremission.Consolidationtherapyinvolvesfurther
chemotherapytreatmentandperhapsabonemarrowtransplant.Thissectionfindsand
clearsthehiddenAMLbloodcellsthatcannotbedetectedbytypicalbloodwork.
(WebMD,2013)

Analysis

Ourteamofradiationtherapists,dosimetrists,oncologynursesandphysiciansallagree

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withthefactthattotalbodyirradiationisanappropriatetreatmentmethodpriortobone
marrowtransplantsofleukemicpatients.Weareallworriedwhenweareacquainted
withourimmunosuppressedpediatricpatientssinceourprocedurefurthersubduestheir
immunesystem.Webelievetotalbodyirradiationisnecessarytoallowforasmooth
stemcelltransplant.ThecancercenterthatLuigireceivedtreatmentisknownfortheir
totalbodyirradiation,especiallytheirpediatricphysicianwhohasbuiltareliable
pediatriconcologyreputationthroughtheircollaborationwiththeChildrenshospital
nextdoors.
TheapproachofradiationtherapyincollaborationwithchemotherapyandATGplayed
aroleforpreparingNarcellasimmunesystemforbonemarrowtransplant.Thepediatric
physicianprescribedtheradiationtomanagethehematopoieticsystembydestroying
theabnormalwhitebloodcellsandaffectedbonemarrowinunisonwithchemotherapy.
NarcellasintravenousadministrationofATGoperatedasabiotherapeutictactictoattack
theTlymphocytesandimprovebloodcountsinanattempttoprepareherforasmoother
reactionthetransplant.
Aftertworoundsofchemotherapyandtotalbodyirradiation,Narcellasbodytoleratedthe
burdenwell.Althoughgraftversushostdiseaseandimmunosuppressioninstigatedafew
bumpsintheroad,Narcellasconditionseemstobesteadilyimproving.Arelapseisdefinitely
notanidealoutcomeforacutemyeloidpatients,butinNarcellascase,afightingdriveisallshe
needs.

CASESTUDY:ACUTEMYELOIDLEUKEMIA

References
AmericanCancerSociety.(2013,July24).Howisacutemyeloidleukemia
diagnosed?Retrievedfrom
http://www.cancer.org/cancer/leukemia
acutemyeloidaml/detailedguide/leukemiaacutemyeloidmyelogenous
diagnosed

AmericanCancerSociety.(2014,July2).LeukemiaAcuteMyeloid
(Myelogenous).Retrievedfrom

13

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http://www.cancer.org/cancer/leukemia
acutemyeloidaml/detailedguide/leukemiaacutemyeloidmyelogenous
riskfactors

CancerResearchUK.(2014,May16).Radiotherapyforacutemyeloid
leukaemia.Retrievedfrom
http://www.cancerresearchuk.org/about
cancer/type/aml/treatment/radiotherapyforacutemyeloidleukaemia

NationalCancerInstitute.(2014,November11).AdultAcuteMyeloidLeukemia
Treatment(PDQ)NationalCancerInstitute.Retrievedfrom
http://www.cancer.gov/cancertopics/pdq/treatment/adultAML/Patient/pag
e114

Seiter,K.(2014,August15).AcuteMyelogenousLeukemia.

Retrievedfrom

http://emedicine.medscape.com/article/197802overview#a0104

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