Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia.
OBJECTIVE
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.
Yang
Yung-Li
YL
Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, ROC.
Lin
Dong-Tsamn
DT
Chang
Sheng-Kai
SK
Lin
Shu-Rung
SR
Lin
Shu-Wha
SW
Chiou
Rong-Jing
RJ
Yen
Ching-Tzu
CT
Lin
Kai-Hsin
KH
Jou
Shiann-Tarng
ST
Lu
Meng-Yao
MY
Chang
Hsiu-Hao
HH
Chang
Wan-Hui
WH
Lin
Kuo-Sin
KS
Hu
Chung-Yi
CY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D013624:Taiwan
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1