precursor b-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and t cell – lineage antigen expression experience from 2022 karthik bommannan.pdf

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Hematology,TransfusionandCellTherapy

1Originalarticle
2PrecursorB-lineageacutelymphoblasticleukemia
3patientswithaberrantnaturalkillercellandTcell
4–lineageantigenexpression:experiencefroma
5tertiarycancercarecenter
∗
6Q5KarthikBommannan,JhansiRaniArumugam,VenkatramanRadhakrishnan,
7JayachandranPerumalKalaiyarasi,NikitaMehra,TenaliGnanaSagar,
8ShirleySundersingh
9Q6CancerInstitute(.),Adyar,Chennai,India
10
11articleinfoabstract
12
13Q7Articlehistory:Introduction:Flowcytometricimmunophenotyping(FCI)playsamajorroleindiagnosing
-lineageacutelym-
15Accepted6August2020phoblasticleukemia(B-ALL),expressionofcertainnon-lineage/crosslineageantigensis
-
17hensivelyanalyzedtheclinicalandlaboratoryprofilesofB-ALLpatientsshowingaberrant
18Keywords:T/naturalkiller(NK)cellantigenexpression.
Materialsandmethods:Thisisaprospectivestudywhere152consecutiveB-ALLpatients
19CD56positiveprecursorBlineage
20acutelymphoblasticleukemiawereanalyzedforaberrantexpressionofT/NKcellantigens(CD1a,CD5,CD4,CD7,CD8and
21CD7positiveprecursorBlineageCD56)-cellantigen-expressingB-ALL
22acutelymphoblasticleukemiapatientswasstatisticallyanalyzedagainstconventionalB-ALLpatients.
23PrecursorBlineageacuteResults:InourB-ALLcohort,CD5,CD7andCD56expressionwereobservedinone,sixand
24lymphoblasticleukemianinepatients,-expressingB-ALLpatientswerepredominantlychildren
(89%)andpresentedasstandardclinicalrisk(p=)diseasewithfrequentETV6-RUNX1
fusion(p=),CD7-expressingB-ALLpatientswereadolescent-
youngadult/adult-ageskewed(83%)andhadanadversecytogeneticprofile(p=),
especiallyforthefrequentpresenceofBCR-ABL1fusion(p=)andKMT2Arearrange-
ment(p=).CD7-expressingB-ALLpatientshadinferiorevent-freesurvival(p=)
thantheirCD56-expressingcounterparts,buttherewasnosignificantdifferenceinthe
overallsurvival(p=).
Conclusion:IncomparisontoconventionalB-ALLpatients,therearesignificantdifferences
intheage,cytogeneticprofileandevent-freesurvivalofT/NK-cellantigen-expressingB-ALL
patients.
©2020Associac¸ao˜BrasileiradeHematologia,
-NC-NDlicense
(-nc-nd//).
∗
Correspondingauthorat:DepartmentofOncopathology,CancerInstitute(,)Adyar,Chennai,600020India.
E-mailaddress:******@().
/
2531-1379/©2020Associac¸ao˜BrasileiradeHematologia,
openaccessarticleundertheCCBY-NC-NDlicense(-nc-nd//).
Pleasecitethisarticleinpressas:BommannanK,-lineageacutelymphoblasticleukemiapatientswithaberrantnatu-
ralkillercellandTcell–lineageantigenexpression:.
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3

Introduction3
wasassessedbytheNationalCancerInstitute(NCI)
Patientsintheagegroup1–18yearsweretreatedwiththe80
25Flowcytometricimmunophenotyping(FCI)playsamajorrole
IndianChildhoodCollaborativeLeukemiaGroup(ICiCLe)pro-81
26inthediagnosisandfollow-upofpatientswithprecursor
tocolandpatientsover18yearsofageweretreatedwiththe82
27Q8B-lineageacutelymphoblasticleukemia(B-ALL).DuringFCI
Berlin-Frankfurt-Muenster95(BFM95)
28diagnosisofB-ALL,expressionofcertainnonB-lineageanti-
(day30)minimalresidualdisease(MRD)assessmentwasby84
29gensareofprognosticsignificanceandprovidecluestowards
≥85
%residualleukemiceventswere
30underlyingmolecular-,

31thecytogeneticandprognosticrelevanceassociatedwith
Thestudywasapprovedbytheethicscommitteeofour87
32aberrantexpressionofmyeloidlineagemarkersinB-ALLhas
88
1,2Instituteandwasconductedadheringtothe1964Helsinki
33beenwelldocumented.
declarationanditslateramendmentsorcomparableethical89
34EnglishliteratureregardingaberrantexpressionofT-cell
,informedconsentwasobtained90
35ornaturalkiller(T/NK)-celllineageantigens(.,CD1a,CD2,
fromthepatients(adults)orfromparentsorlegalguardians91
36CD4,CD5,CD7,CD8andCD56)inB-ALLpatientsdatesback
92
2–13(patientsunder18yearsofage).
,
(18caseseach)
39ofT/NKcellantigen-expressingB-ALLpatients,withonlyStatistics
-laboratorypro-
2,3
41fileofthesepatientsagainstconventionalB-
42RegardingtheseT/NKcellantigen-expressingB-ALLpatients,andthestatisticalpackageforsocialsciences(version23;IBM,94
43individualantigen-wiseclinical-hematologicprofilesandArmonk,NY).Forintergroupcomparisons,theFisher’sexact95
-andMann–-96
45Q9rentmanuscript,wehavedocumentedourexperiencewitheasediagnosisasastartingtimepoint,Kaplan–Meierstatistics97
46CD1a,CD4,CD5,CD7,CD8andCD56antigenexpressioninwasusedtodetermineoverallsurvival(OS)andevent-freesur-98
≥
47patientswithB-ALLandhavecomparedtheclinicopathologicvival(EFS).Treatmentinductionfailure(5%bonemarrow99
48relevanceassociatedwithaberrantexpressionoftheseindi-blasts),diseaserelapse,ordisease-relateddeathwerecon-100

determinedbytheCoxproportionalhazardmodel(Waldtest)102
usingthefollowingco-variates:NCIriskatdiagnosis,cyto-103
geneticrisk,end-inductionMRDstatus,CD7expressionand104
Materialsandmethods
-tailedandcon-105
sideredsignificantatap-value≤
50Thisstudy,inwhichalltreatment-naïveB-ALLpatientsdiag-
51nosedbetweenNovember2017andSeptember2019were
52included,
53Patientsintheagegroupof1–14years,15–29yearsand
54>30yearswereconsideredaspediatric,adolescents-youngDuringthestudytimeframe,152treatment-naïveB-ALL107
55adults(AYAs)andadults,-ALLwaspatientswerediagnosedatourInstitute(Table1).Among108
56bymorphologicassessmentofRomanowsky-stainedbonethesepatients,14optedagainsttreatment,3diedduring109
57marrowaspirationandperipheralbloodsmears,followedbytheinductionphaseoftreatmentandtheremaining135110
(supplementaryTableS1)andpatientsweretestedforend-
59sampleprocessingstepsareasdescribedinourpreviouspatientsforwhomconventionalkaryotypingwasperformed,112
14
,
61CD1a,CD4,CD7,CD5,CD8andCD56wereevaluatedontheforBCR-ABL1,ETV6-RUNX1&TCF3-PBX1fusionsandKMT2A114
62leukemicB-lymphoblastsidentifiedbysequentialgatingstrat--115
,ablefollow-uphadthedurationof10months,rangingfrom1116
64normalB,TandNKlymphocyteswithineachcorrespond-
≥
%Amongthese152patients,aberrantexpressionofCD5,CD7118
66leukemicblastsexpressinganantigenofinterestwerecon-andCD56wasseenin1(%),6(4%)and9(6%)patients,119
2,3
(Figure1andTable1).Noneofourpatientshad120
68surfaceCD10expressiononblastswereclassifiedas‘protheexpressionofCD4,CD8,CD1aortheco-expressionofany121
69B-ALL’-hematologicprofile122
70categorizedas‘otherprecursorB-ALL’(n=16)withaberrantT/NKcell123

72cytogeneticsandinterphasefluorescenceinsituhybridiza-
73tion(i-FISH)toidentityBCR-ABL1fusion,ETV6-RUNX1fusion,CD56-expressingB-ALLpatients125
74E2A--riskcytoge-
75neticswasdefinedbythepresenceofeitherBCR-ABL1fusion,AmongCD56-expressingB-ALLpatients(CD56+B-ALL),the126
76KMT2Arearrangement,hypo-diploidyorcomplexkaryotypemedianageatdiagnosiswas7years,rangingfrom2to62,127
≥

Pleasecitethisarticleinpressas:BommannanK,-lineageacutelymphoblasticleukemiapatientswithaberrantnatu-
ralkillercellandTcell–lineageantigenexpression:.
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Q1Q2Q3
Not
NA:


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patients.
disease;
B-ALL
CD7+
vs
-value
CD7-
P
residual


and
CD7+
Minimal
CD7-CD56+
vs
MRD:
between



CD56-CD7+
Compared
Hemoglobin;
71)98)
b
vs
98)
−−
−
(–175)
Hb:
(33)(17)(33)(0)(100)(83)(40)(17)(17)(0)(67)(67)(17)(17)(50)
(3–50)(5–10)(15(66(5
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and
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expression
563)99)
the
(45)(38)(30)(15)(12)2/6(62)(10)(10)(2)(4)(13)(40)(9)(17)4/61/6
98)
(4)(3)(1)0/6(1)0/6(2)0/6(3)
CD56+
−−
−
(.3–587)
CD7
(100)
(–64)(22–149)(10(55(6
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:
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marrow;
)
CD56
457)
(65)
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97)
−
88)
−
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146)
(44)(44)(44)(0)66/146(0)(0)(0)(0)4/118(0)(0)1/118(22)1/118(33)(0)(0)(0)()(0)(0)52/129(0)12/129
(
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their
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CD7-(n
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BM:
expression
cell.
586)
−
563)
(44)(36)4/9(28)(68)(16)(12)(65)(13)(9)(3)(4)(17)(42)3/8(10)(19)0/8
94)84)
CD56
blood
respect
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−
−−
(
leukemia;
9)
in
(–64)(10
=
(5)
:1773(25–149)(7850(1152/14341/1435/12984/12418/11514/1152/11593/14316/12411/12404/12405/12421/1245/12725/130
CD56+(n
White
WBC:
patients,
99)
(44)(37)63/143(30)(14)(11)(3)(1)4/115(1)1/115(2)1/115()(12)()(3)(4)(16)(41)(4)53/127(10)(18)13/127
98)
(4)
−
lymphoblastic
−
(–587)
152)143)
patients
blood;
(–64)10(22–149)(10–563)(55(4
==
(5)
B-ALL
18/124
14/12404/12401/12402/124
(n
AllCD56-(:
Diploid
acute
our
of
Peripheral
lineage
(%)
Triploid01/124
B
PB:
profile
Ploidy
HyperdiploidHigh
AYAAdult
HyperdiploidLowHypodiploidHighHypodiploidLowNearNearTetraploid
Pediatric
B-ALL:
institute;
/L
(%)
9
adult;
(%)
(%)56/135
/L
9
X10
(%)
laboratory
cancer
(%)16/133
%
%
X10
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years10
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and
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positive
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blast
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in
blast
at
positive
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HbPlateletBMPB