This study is to find out distribution of genetic polymorphisms and genes related to the chemotherapeutic drugs of ALL.
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.
Study Type
OBSERVATIONAL
Enrollment
200
Seoul National University Hospital
Seoul, Chongno-gu, South Korea
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.
Time frame: up to 3 years from diagnosis
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.
Time frame: 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.
Time frame: 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.
Time frame: up to 3 years from diagnosis
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