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Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia
Author(s) -
Yang YungLi,
Lin DongTsamn,
Chang ShengKai,
Lin ShuRung,
Lin ShuWha,
Chiou RongJing,
Yen ChingTzu,
Lin KaiHsin,
Jou ShiannTarng,
Lu MengYao,
Chang HsiuHao,
Chang WanHui,
Lin KuoSin,
Hu ChungYi
Publication year - 2010
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22292
Subject(s) - pharmacogenomics , medicine , oncology , pharmacogenetics , hazard ratio , confounding , genotype , pharmacology , gene , genetics , confidence interval , biology
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. Pediatr Blood Cancer 2010;54:206–211. © 2009 Wiley‐Liss, Inc.