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.
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.
Authors: J Gregers; H Gréen; I J Christensen; K Dalhoff; H Schroeder; N Carlsen; S Rosthoej; B Lausen; K Schmiegelow; C Peterson Journal: Pharmacogenomics J Date: 2015-01-13 Impact factor: 3.550