1. Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia.
- Author
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Yang YL, Lin DT, Chang SK, Lin SR, Lin SW, Chiou RJ, Yen CT, Lin KH, Jou ST, Lu MY, Chang HH, Chang WH, Lin KS, and Hu CY
- Subjects
- Asian People genetics, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Multivariate Analysis, Pharmacogenetics, Proportional Hazards Models, Retrospective Studies, Survival Analysis, Taiwan, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Drug Resistance genetics, Polymorphism, Genetic, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Objectives: This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population., Methods: A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression., Results: Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively., Conclusions: Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients., ((c) 2009 Wiley-Liss, Inc.)
- Published
- 2010
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