Clinical Trial: Functional Pharmacogenomics of Childhood Acute Lymphoblastic Leukemia in Taiwan

Study Status: Withdrawn
Recruit Status: Unknown status
Study Type: Observational

Official Title: Functional Pharmacogenomics of Childhood Acute Lymphoblastic Leukemia in Taiwan

Brief Summary:

Emerging results suggest that a cure rate of nearly 90 percent will be attained in the near future. The advance was attributed to stringent application of prognostic factors for risk factor-directed therapy. Early response to treatment has greater prognostic strength than does any other biologic or clinical feature tested to dates. The measurement of minimal residual disease(MRD) affords a level of sensitivity and specificity that cannot be attained through traditional microscopic morphologic assessments. In Taiwan, detection for the most recurrent fusion genes and the MRD were not commonly available, the TPOG(Taiwan Pediatric Oncology Group) used clinical features, immunophenotypes, and cytogenetics to do risk group classifications and protocol assignment. A successful rate of 60-70% has been reached. In order to improve the cure rate of ALL in Taiwan, this project aims at establishing the methods for better risk classifications and establishing MRD detection for risk-directed therapy for childhood ALL in Taiwan.Intrinsic and acquired resistances to multiple anticancer agents represent major obstacles and accounts for 10-20% of treatment failure in the developed countries nowadays. Recent progress using DNA microarray identified differential expression level of the genes known to implicate in cell cycle control, DNA repair and apoptosis in different subsets of ALL patients, which were found to be related to drug response. Genetic polymorphisms in the genes of drug-metabolizing enzymes, drug transporters or drug targets, can influence the efficacy or toxicity of antileukemic agents. Specific genotype might be important in determining the pharmacokinetic effects of one population or disease subtype from that in others. Recently, the expression profiles of relatively few microRNAs (miRNAs) (~200 genes), was noted to accurately classify human cancers. These informations hinted that expression of the genes in the leukemic ce

Detailed Summary:

In the 1990s, the five-year event-free survival rates for childhood ALL generally ranged from 70 to 83 percent in developed countries, with an overall cure rate of approximately 80 percent. Emerging results suggest that a cure rate of nearly 90 percent will be attained in the near future. Progress in the treatment of ALL, however, has been made largely by the optimization of the use of existing medicines rather than by the discovery of new agents. These factors predicting clinical outcomes include treatment regime, clinical features, global gene expression patterns and genetics of leukemia cells, host pharmacodynamics and pharmacogenetics, early response to treatment. In Taiwan, detection the most recurrent fusion gene occurred in ALL were not popular applied yet. Minimal residual disease (MRD) detection is not commonly available for the evaluation of initial response to chemotherapy protocol we have assigned. The TPOG (Taiwan Pediatric Oncology Group) use only clinical features (age, PB white blood counts, immunophenotypes, and cytogenetics) to assign the protocols. Only around 60-70% of patients were successful treated. The ultimate goal of this project is to establish the methods for better risk classifications for pediatric ALL patients in Taiwan in order increase cure rate.

Classification of childhood ALL by molecular methods Risk factors based on a patient's physical manifestations or hematologic and biochemical tests have been largely replaced by more specific tests of the biologic features of leukemic cells. The recently introduced World Health Organization (WHO) classification takes into consideration of morphologic and immunologic features plus well-studied, common nonrandom chromosomal abnormalities that clearly influence the laboratory and clinical features of ALL. Genetic makeup of the leukemic cells has been recognized as the most important prognostic factor
Sponsor: National Taiwan University Hospital

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Information By: National Taiwan University Hospital

Dates:
Date Received: September 4, 2007
Date Started: March 2007
Date Completion: December 2009
Last Updated: September 5, 2007
Last Verified: December 2005