With Down Syndromw

8/2/2019 With Down Syndromw

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Outcome and Toxicity of Chemotherapyfor Acute Lymphoblastic Leukemia in

Children With Down Syndrome

Niketa Shah, MD, Ali Al-Ahmari, MD, Arwa Al-Yamani,MD, Lee Dupuis,MscPhm,ACPR,FCSHP,RPh, DerekStephens,MSc, and Johann Hitzler,MD,FRCPC,FAAP

Presented by : Nucky Vera Arnaz, S.Ked

Rilahi Zahrah Harahap, S.KedAdvisor : dr. Dian PS, SpA


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INTRODUCTION

Children with Down syndrome (DS) have a10-to 24 fold higher risk of developing acutelymphoblastic leukemia (ALL) than the

general pediatric population Dilemma of treating ALL in children with DS

Toxic effect of metrotrexate

Outcome and toxicity of chemotherapy forALL in children with DS


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MATERIALS AND METHODS


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Patients and Treatment

Participants: 30 patiens with DS and ALL weretreated at The Hospital for Sick Children,Toronto,Canada between 1985-2004

Diagnosed for DS: clinical features and a bloodcell karyotype

Diagnosed for ALL: blast morpholgy,immunophenotype, karyotype, expression of

fusion transcript.


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Study Design

Cohort of 30 children with DS and ALL, wascompared with 60 Non DS (NDS) control patientwith ALL, who were matched for diagnosis, age,

sex, year of diagnosis, and treatment protocol. Grade 3 and 4 adverse events, and days of

hospitalization due to toxicity were documented


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Metrhotrexate elimination times wereextracted from pharmacy records.

During maintenance therapy

number ofdays, which oral anti-metabolitechemotherapy, total number of suchtreatment interruption were recorded


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Statistical Analysis

Event Free Survival (EFS) date ofdiagnosis to the date of the first event

Overall Survival (OS) date of diangosis to

the date of death or last follow up OS and ESF were compared between

between the DS and NDS group of patientswith ALL.


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Cox proportional hazard (CoxPH)correlated data, outcomes involving time toevent

Generalized linear model (GLM) survivaland non-survival outcome.

T-test, F-test, Chi square test analysis of

methrotrexate elimination times


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RESULT


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Clinical Characteristics of DSALL


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METHODS

Data Analysis The statistics were performed by using SPSS

11.0.

The difference between the group of childrenwith DSLDs and the normative population withrespect to the proportion of children with motorproblems was assessed with the 2 test.

To assist in determining the meaningfulness ofgroup effects, correlational effect size statisticsfor nonparametric data were calculated foreach dependent variable.


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DISCUSSION

Developmental variation in brain structures andfunctions variation in abilities underscoringthe interrelatedness of developmental disorders.

Possible mechanisms underlying the presentfindings: Brain structures : basal gangliacaudate

nucleus (has a strong functional relationshipwith the prefrontal cortex)

Damage to 1 of these regions decline in thecontrol and execution of movementscombined with cognitive deficits, among whichare specific language disturbances.


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Environmental factors:

Children with DSLDs communicationdifficultiesinfluence social acceptance

participate less in play with peers. Consequence lack of practice of motor

skillslow levels of motor skills.

DISCUSSION


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Subgroups differed in motor performance: language disorders >speech disorders & both:

on the ball-skills subtest and total test,

language disorders > both : on the balancesubtest Tendency speech disorders to perform worse

than language disorders Only 14 children with speech disorders

participatedlack of significance. When speech production is affected, motor

problems are more pronounced.

DISCUSSION


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The reason ? Different neural circuits in which brain

structures participate.

That having both disorders has a greaterimpact on social functioning and socialbehavior than only language disordersbecause of the more complicatedcommunication.

Motor problems were evident in a largeproportion of children aged 6 yearsintervention at an early age is warranted

DISCUSSION


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DISCUSSION

Information provided by the Movement ABC may behelpful in deciding to provide interventions or not: < 5th percentile intervention is imperative, but the mode

and type may vary.

5th - 15th percentile decision to intervene has to dependon the impact of the childs motor problems on both dailylife motor functioning, as well as other developmentalareas, such as social functioning.

A delimitation of this study was the small samplesize of the children with only speech disorders andthe missing information about the etiology of thedisorders.


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RESULTS

Compared with the norms, children with developmentalspeech and language disorders performed significantly lesswell.

51% of the children with developmental speech and language

disorders had borderline or definite motor problems. Children with language disorders had better performance on

the ball-skills subtest and the total test than children withspeech disorders and children with both speech and languagedisorders.

Children with language disorders had significantly betterperformance on the balance subtest than children with bothspeech and language disorders.


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CONCLUSIONS

Developmental speech and language disorders are frequentlyassociated with motor problems and that the kind ofdevelopmental speech and language disorders affects motorperformance differently.

Speech and language disorders more impact on motorperformance

When speech production is affected, motor problems aremore pronounced.

The findings support the need to give early and more

attention to the motor skills of children with developmentalspeech and language disorders in the educational and homesetting, with special attention to children whose speech isaffected.

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