Rev. Bras. Hematol. Hemoter. vol.39 número1

rev bras hematol hemoter. 2017;39(1):77–79

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

report

Isolated

skin

relapse

of

Philadelphia

chromosome-positive

acute

lymphoblastic

leukemia

after

allogeneic

stem

cell

transplant

Masumi

Ueda

_,

_Carlos

_Silva

_,

_Linda

_Baer

_,

_Paolo

_F.

_Caimi

_,

_Kevin

_Cooper

_,

Kord

Honda

_,

_Marcos

_de

_Lima

a_{UniversityHospitalsSeidmanCancerCenter,Cleveland,UnitedStates}

b_{CaseWesternReserveUniversity,Cleveland,UnitedStates}

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Articlehistory:

Received14October2016 Accepted7November2016 Availableonline30December2016

Introduction

Leukemiacutisisarareentitydiagnosedinonly1–3%of T-andB-cellacutelymphoblasticleukemia(ALL).1,2 _Aleukemic leukemia cutis (ALC) is an even rarer diagnosis, occurring withoutleukemiccellsinthebloodormarrow,often preced-ing systemicdisease.2,3 _{ThePhiladelphia chromosome(Ph)} isoneofthemostcommonchromosomalabnormalities in adultB-ALLpatientsandisassociatedwithpoorprognosis. Althoughtheuseoftyrosinekinaseinhibitors(TKIs) target-ingtheoncoproteinbreakpointclusterregion-Abelsonmurine leukemia1(BCR-ABL1)hasdramaticallyimprovedoutcomes, allogeneichematopoieticstemcelltransplant(HSCT)isstill recommendedforalleligiblepatients,withrelapseafterHSCT remaininga major cause of treatment failure.4 _{Herein we} reportacaseofisolatedskinrelapseofPh-positivepre-Bcell ALLafterallogeneicHSCT.

∗ _{Correspondingauthorat:UniversityHospitalsSeidmanCancerCenter,11100EuclidAvenue/SCC1015,Cleveland,OH44106,United} States.

E-mailaddress:marcos.delima@uhhospitals.org(M.deLima).

Case

report

A26-year-oldmanreceivedamatchedrelateddonor periph-eral blood HSCT for Ph-positive pre-B cell ALL in first remission. PriortoHSCThehad achievedcomplete molec-ularremissionaftertwocyclesofimatinibandtheregimen rituximab with hyperfractionated cyclophosphamide, vin-cristine, doxorubicin, and dexamethasone alternating with methotrexateandcytarabine(R-HyperCVAD).Remissionwas consolidatedwithanallogeneictransplantfromhishuman leukocyte antigen (HLA)-matched sibling using cyclophos-phamide and 12Gy total body irradiation conditioning. Graft-versus-host disease (GvHD) prophylaxis consisted of tacrolimusandmethotrexate.Hispost-HSCTcoursewas com-plicatedbychronicGvHDinvolvingthelungs,liver,skinand lacrimal glands; he was treated with extracorporeal pho-topheresis, tacrolimus and prednisone. An isolated 2-cm

http://dx.doi.org/10.1016/j.bjhh.2016.11.003

78

Figure1–Isolated,2.5cm×1cmraisedskinlesiononthescalpvertex.

Figure2–(A)Hematoxylinandeosinstainofskinlesion(400×magnification).(B)CD19immunohistochemistrystainof

skinlesion(400×magnification).

erythematous and elevated scalp skin nodulewas noticed 15monthsaftertransplant(Figure1).Biopsyshowed atypi-calmonomorphousmononuclearcellsinfiltratingthedermis and subcutaneous fat (Figure 2A); the cells stained posi-tive for CD19 (Figure 2B), CD34, TDT, CD10, and PAX5 by immunohistochemistry,consistentwithALL. There wasno evidenceofsystemicdiseaseinexamsofthebonemarrow, peripheral blood or cerebrospinal fluid, byflow cytometry, cytogenetics, or in an investigation of the BCR-ABL1 gene byfluorescent in situ hybridization (FISH)and quantitative reverse transcriptase polymerase chainreaction (qRT-PCR), orbywhole-bodypositronemissiontomography(PET)scan andbrainmagneticresonanceimaging.Stableengraftment with full donor chimerism was observed. Next generation sequencingofbiopsytissuetargetingalargepanelofknown

hematologic malignancy mutations showed the BCR-ABL1 fusiongeneandadditionalgenomicalterationsofunknown significance (FoundationOne Heme, Cambridge, MA).5 _Skin FISH testing also showed the BCR-ABL1 fusion. Treatment consistedoflocalradiation(24Gy),followedbydasatinib,an inhibitoroftheAbl,Srcandc-Kitkinases.Thepatientremains inremission25monthsafterHSCT,whileonchronicGvHD treatment.

Discussion

and

conclusion

revbrashematolhemoter.2017;39(1):77–79

79

Ofthese,onlyonecasedescribedALCrelapseofB-ALLafter allogeneictransplantation.3_{Remarkably,ourpatienthasno} detectablesystemicdiseasedespitetheavailabilityof sensi-tivemoleculartests.Inaddition,thetranslocation(9;22)and theBCR-ABL1geneweredetectedonlyintheskin,allowing targetedtreatmentoftherelapse.Long-termprognosisofALC recurrence afterallogeneic HSCT and the potential benefit oftyrosine-kinaseinhibitortherapyinadditiontothe graft-versus-leukemiaeffectsareunknown.

Ethical

statement

ThisprotocolwasapprovedbytheInstitutionalReviewBoard ofUniversityHospitalsClevelandMedicalCenter,andthe sub-jectgavewritteninformedconsent.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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1.Campuzano-GarciaAE,Torres-AlvarezB,Castanedo-Cazares JP.Leukemiacutisinapatientwithpre-B-cellacute lymphoblasticleukemia.JAADCaseRep.2015;1(6):364–7. 2.Cho-VegaJH,MedeirosLJ,PrietoVG,VegaF.Leukemiacutis.

AmJClinPathol.2008;129(1):130–42.

3.AnsellLH,MehtaJ,CotliarJ.Recurrentaleukemicleukemia cutisinapatientwithpre-B-cellacutelymphoblastic leukemia.JClinOncol.2013;31(20):e353–5.

4.GiebelS,CzyzA,OttmannO,BaronF,BrissotE,CiceriF,etal. Useoftyrosinekinaseinhibitorstopreventrelapseafter allogeneichematopoieticstemcelltransplantationfor patientswithPhiladelphiachromosome-positiveacute lymphoblasticleukemia:apositionstatementoftheAcute LeukemiaWorkingPartyoftheEuropeanSocietyforBloodand MarrowTransplantation.Cancer.2016;122(19):2941–51. 5.FoundationOneHemeTechnicalInformationandTest

Overview[cited2016July24].Availablefrom: