Outcome and Toxicity of Chemotherapy for 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, Derek Stephens,MSc, and Johann Hitzler,MD,FRCPC,FAAP Presented by : Nucky Vera Arnaz, S.Ked Rilahi Zahrah Harahap, S.Ked : dr. Dian PS, SpA

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INTRODUCTION

Children with Down syndrome (DS) have a 10-to 24 fold higher risk of developing acute lymphoblastic leukemia (ALL) than the general pediatric population Dilemma of treating ALL in children with DS Toxic effect of metrotrexate Outcome and toxicity of chemotherapy for ALL in children with DS

MATERIALS AND METHODS

Patients and Treatment

Participants: 30 patiens with DS and ALL were treated at The Hospital for Sick Children, Toronto,Canada between 1985-2004 Diagnosed for DS: clinical features and a blood cell karyotype Diagnosed for ALL: blast morpholgy, immunophenotype, karyotype, expression of fusion transcript.

Study Design

Cohort of 30 children with DS and ALL, was compared with 60 Non DS (NDS) control patient with 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

Metrhotrexate elimination times were extracted from pharmacy records. During maintenance therapy number of days, which oral anti-metabolite chemotherapy, total number of such treatment interruption were recorded

Statistical Analysis

Event Free Survival (EFS) date of diagnosis 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 patients with ALL.

Cox proportional hazard (CoxPH) correlated data, outcomes involving time to event Generalized linear model (GLM) survival and non-survival outcome. T-test, F-test, Chi square test analysis of methrotrexate elimination times

RESULT

Clinical Characteristics of DS ALL

METHODS
Data Analysis The statistics were performed by using SPSS 11.0. The difference between the group of children with DSLDs and the normative population with respect to the proportion of children with motor problems was assessed with the 2 test. To assist in determining the meaningfulness of group effects, correlational effect size statistics for nonparametric data were calculated for each dependent variable.

DISCUSSION

Developmental variation in brain structures and functions variation in abilities underscoring the interrelatedness of developmental disorders. Possible mechanisms underlying the present ndings: Brain structures : basal ganglia caudate nucleus (has a strong functional relationship with the prefrontal cortex) Damage to 1 of these regions decline in the control and execution of movements combined with cognitive decits, among which are specic language disturbances.

DISCUSSION

Environmental factors: Children with DSLDs communication difculties inuence social acceptance participate less in play with peers. Consequence lack of practice of motor skills low levels of motor skills.

DISCUSSION

Subgroups differed in motor performance: language disorders >speech disorders & both: on the ball-skills subtest and total test, language disorders > both : on the balance subtest Tendency speech disorders to perform worse than language disorders Only 14 children with speech disorders participated lack of signicance. When speech production is affected, motor problems are more pronounced.

DISCUSSION

The reason ? Different neural circuits in which brain structures participate. That having both disorders has a greater impact on social functioning and social behavior than only language disorders because of the more complicated communication. Motor problems were evident in a large proportion of children aged 6 years intervention at an early age is warranted

DISCUSSION

Information provided by the Movement ABC may be helpful 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 depend on the impact of the childs motor problems on both daily life motor functioning, as well as other developmental areas, such as social functioning.

A delimitation of this study was the small sample size of the children with only speech disorders and the missing information about the etiology of the disorders.

RESULTS

Compared with the norms, children with developmental speech and language disorders performed signicantly less well. 51% of the children with developmental speech and language disorders had borderline or denite motor problems. Children with language disorders had better performance on the ball-skills subtest and the total test than children with speech disorders and children with both speech and language disorders. Children with language disorders had signicantly better performance on the balance subtest than children with both speech and language disorders.

CONCLUSIONS

Developmental speech and language disorders are frequently associated with motor problems and that the kind of developmental speech and language disorders affects motor performance differently. Speech and language disorders more impact on motor performance When speech production is affected, motor problems are more pronounced. The ndings support the need to give early and more attention to the motor skills of children with developmental speech and language disorders in the educational and home setting, with special attention to children whose speech is affected.