Rev. Bras. Hematol. Hemoter. vol.37 número3

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rev bras hematol hemoter. 2015;37(3):207–210

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Central

retinal

vein

occlusion

as

first

manifestation

of

relapse

in

acute

lymphoblastic

leukemia

Flávia

Kessler

Borges,

Júlia

Biegelmeyer,

Samantha

Thifani

Alrutz

Barcelos

∗

_,

Raquel

Cristine

Breunig

UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre(UFCSPA),PortoAlegre,RS,Brazil

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Articlehistory:

Received6November2014 Accepted31December2014 Availableonline14April2015

Introduction

Retinal vein occlusion is the second most common cause ofvisualloss dueto retinalvascular disease afterdiabetic retinopathy.1 _Among _the _risk _factors _described, _it _is _well knownthatthehypercoagulablestatepresentinneoplasias canculminateinveinocclusion.Itisdescribedthatanyocular structuremay beinvolvedinacuteleukemia2_; _involvement of the choroid and retina is the most common. However, leukemic cells can infiltrate the conjunctiva and lacrimal glands,producingobviousmasses.Kareshetal.publisheda twoyearprospectivestudy ofnewly diagnosedadultswith acutemyeloidleukemia;64%ofpatientshadretinaloroptic nerve abnormalities where hemorrhages and cotton wool spots(aconsequenceofnervefiberischemia)werethemost frequentfindings.3 _The_association _between_central _retinal vein occlusion and acute lymphoblastic leukemia (ALL) relapsehasrarelybeendescribedthough.4–6_We_hereby_report

∗ _{Corresponding}_author_at:_Rua_Sarmento_Leite,_245,_Centro,_90050-170_Porto_Alegre,_RS,_Brazil.

E-mailaddress:samanthatifani@gmail.com(S.T.A.Barcelos).

a case of central retinal vein occlusion as the presenting manifestationofrelapseinALL.

Case

report

A59-year-oldfemalewasdiagnosedwithALLinNovember 2013.Atthattime,shehadthefollowinglaboratoryresults: hemoglobin:8.7g/dL;redbloodcells:2.95×109/␮L;MCV:89fL; total leukocytes: 18.66×109/L; lymphocytes: 5.374×109/L;

segmented neutrophils: 2.930×109/L; blasts: 9143cells/␮L; uric acid: 5.2mg/dL; lactic dehydrogenase: 1672U/L; creati-nine: 3.1mg/dL; and urea: 83mg/dL. She received volemic resuscitation for tumor lysis syndrome. Subsequently, she developed pneumonia caused by Cryptococcus neoformans and herpeszoster skin lesions.Treatment was made with meropenem, amphotericin and acyclovir. In January 2014, aftercompletingtreatmentfortheinfections,shewas sub-mitted to chemotherapy induction using the hyperCVAD

http://dx.doi.org/10.1016/j.bjhh.2015.03.008

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revbrashematolhemoter.2015;37(3):207–210

Figure1–Fluoresceinangiographyshowingocclusionofcentralretinalvein.

regimen–courseA(cyclophosphamide,vincristine, doxoru-bicinand dexamethasone).Immunophenotypingperformed inFebruary2014showedremissionofthedisease.

In March 2014 she presented febrile neutropenia and typhlitis.Empirictreatmentwithcefepimewasstartedand the hyperCVAD regimen was interrupted. Blood cultures

identifiedEscherichia coliandKlebsiellapnemoniae. Treatment wascompletedonApril20th2014.

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tocompletethefourthcycleoftherapyduetohematological toxicity(hemoglobin:9.0g/dL;redbloodcells:2.71×109/␮L; totalleukocytes:0.870×109/L;neutrophils:0.628×109/L;and

platelets:13×109/L).

In August 2014 she came to our hospital emergency departmentcomplainingofaheadacheoftheright sideof her head, sensitivity to light, nausea, vomiting and visual lossinthe right eyethathad started four dayspreviously. Theneurological exam showed no abnormality, except for the eye fundus examination, which revealed papilledema, intraretinal peripapillary and inframacular hemorrhage in the right eye.The left eye presented a pre-retinal hemor-rhage.

Laboratory exams did not reveal any abnormality. A coagulation panel showed platelets 154×109/L;

prothrom-bin time activity: 100%; international normalization ratio (INR): 1.00; and activated partial thromboplastin time: 36.6s.

Anuclearmagneticresonanceimage(MRI)wasmade,and theonlyabnormalitywasahypointenselesionevidencedin theT2sequenceintherighttemporalposteriorregion,which wasprobablyasequelaeofaprevioushemorrhagicinfarct.

Shewasthensubmittedtoafluoresceinangiographythat revealedocclusionofthecentralretinalvein(Figure1).

Inordertoexcludeanyinfectiousetiology,alumbar punc-turewasmade,withanormalopeningpressure(150cmH2O). Cerebrospinal fluid analysis evidenced low glucose lev-els (28mg/dL and 89mg/dL in blood); high protein levels (89mg/dL); cellularity 2520cells/␮L; 94% blasts; 5% mono-cytes;and redbloodcells:220cells/␮L.Culturesforfungus, bacteriaandcytomegalovirusantigenemiaandherpesvirus polymerasechainreaction(PCR)wereallnegative.

Shewasnottakinganydrugthatwouldpotentiallybe capa-bleofinducingretinalveinocclusion.

Inordertocompletetheevaluationofpossible intracere-bralveinthrombosis,thepatientwassubmittedtoavascular MRIthatrevealedthickeningoftherightopticnerveandoptic chiasmprotuberance.

Immunophenotypingoftheliquorhad predominanceof CD10,CD19,DC22,CD34,HLADRcells,suggestingBlineage ALL. Lymphoblasts were identified in the cytopathological examandbonemarrowcytologyconfirmedmedullar infiltra-tion.

Afterconfirming neurologicalrelapse ofALL,intrathecal chemotherapy was given with dexamethasone, cytarabine andmethotrexate.Shehadcompleteremissionofheadache, buthadnoimprovementofhervisualloss.

Amagneticresonanceangiographyofthecentralnervous system(CNS)wascarriedouttoexcludeotherpossible vas-cularthrombosis,butnoalterationwasfoundintheexam, exceptforinfiltrationoftherightopticnerve.

Shewas dischargedfrom hospitalaftertwo sessions of intrathecal chemotherapy, and continues outpatient treat-ment.

Discussion

Therearefewcasesreportedintheliteratureshowingocular nerveinfiltrationasanisolatedmanifestationofALLrelapse,

even thoughit is aconsequenceof CNSinvolvementwith severeprognosis.Inthecasereportedherein,thepatienthada headacheassociatedwithvisualloss,whichstronglysuggests CNS damage.Onceher ophthalmologic exam showedonly centralretinalveinocclusion(CRVO),theclinicaldiscussion focusedontheetiology oftheunderlyingprocess:whether it was aconsequenceofa hypercoagulablestateor dueto directinvasionofneoplasticcellssincebothconditionscan culminateinCRVO.

Inordertoelucidatethisquestion,amagneticresonance angiography wasperformed toexcludeother possiblevein occlusionsintheCNS,buttheonlyfindingwasopticnerve infiltration,whichhadnotbeenevidentuntilthismoment. IthasalreadybeendescribedthatMRIisusefulintheearly detectionofocularinvolvement.7

EventhoughCRVOisrelatedwithanhypercoagulablestate, allthecasesdescribedintheliteraturethatassociateCRVO withALLaresecondarytoaninfiltrationofleukemiccells.4–6 Allcasesshowinfiltrationoftheopticdiskprecedingvessel occlusion.

Treatmentdescribedinthesecasesconsistsinintrathecal chemotherapyandradiotherapy.8,9_There_is_no_benefit_in pre-scribingvascularendothelialgrowthfactor(VEGF)inhibitors inthesecases,asthereiscombineddamageofthevein cir-culationandtheopticnerveconduction;thelattercancause irreversiblevisualloss.10

Conclusion

CNSrelapsecanprecedehematologicalsignsandsymptoms, and regular ophthalmologic exams should be instituted in patients withALL. If ocularsymptomsare presentand the ophthalmologicexamisnormal,aMRIshouldbeconsidered. In cases of ALL and retinal vessel occlusion, always con-sideropticnerveinfiltrationandrapidlyinstitutetreatment withintrathecalchemotherapyandradiotherapytoavoid irre-versibledamage.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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