Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This study is to find out distribution of genetic polymorphisms and genes related to the chemotherapeutic drugs of ALL.

Detailed Description
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Cure rate of pediatric ALL dramatically improved over 80%. Resistance to drug and hematologic relapse are remaining problem in ALL treatment. One of the explanations of drug resistance and toxicities is the pharmacogenetic effect. Germline polymorphisms in genes that code for proteins involved in the pharmacokinetics and pharmacodynamics of antileukemic agents are various, and inter-patient variability is the main factor for pharmacogenetic difference. Since multiple chemotherapeutic agents are involved in treating ALL, many genes related to the metabolic pathways of those drugs have an effect on the pharmacokinetics of patients with ALL. In Korea, pharmacogenetic study including multiple genetic loci for pediatric ALL has not been reported.In this study, the distribution of genetic polymorphisms and genes related to antileukemic drugs were analyzed, and their relations to the outcome of treatment and relapse rates were assessed.

Official Title
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Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of acute lymphoblastic leukemia In case of informed consent and assent Exclusion Criteria: Paients or parents refusal

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pharmacogenetic analysis, ALL<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To find out distribution of genetic polymorphisms genes related to the pharmacodynamics of the ALL therapy | The distribution of each genetic polymorphism is descriped. The differences in genetic polymorphism between risk groups (high vs. standard) are analyzed using the chi-square test or Fisher's exact test. | up to 3 years from diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To see the ethnic difference of genetic polymorphisms related to the chemotehrapeutic drugs of ALL | • The differences in genetic polymorphism between other populations (Korean vs. Western or Japanese) are analyzed using the chi-square test or Fisher's exact test. | whenever after diagnosis and genetic analysis (no time frame needed) | 
| To find out relation of genetic polymorphisms and clinical outcome (relapse or survival) | - Event-free and overall survival are estimated using Kaplan-Meier analysis, and the survival differences according to different genetic polymorphisms and prognostic variables are analyzed by log-rank test. | up to 3 years from diagnosis | 
| To find out risk factors of relapse and death | - Multivariate analysis is conducted with Cox proportional hazards regression model to analyze predictive factors. For the multivariate analysis, all significant univariate variables are entered in a stepwise, forward-selection protocol. | up to 3 years from diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia, single nucleotide polymorphism