BACKGROUND: 6-Mercaptopurine (6-MP) is used for the treatment of pediatric acute lymphoblastic leukemia (ALL). Mutations in the TPMT gene may influence the efficacy and safety of 6-MP treatment. This multicenter study investigated the association between TPMT genotype, 6-MP dose adjustments, and the incidence of adverse effects in patients. PROCEDURE: A total of 203 ALL children were genotyped using PCR/allele-specific amplification and PCR/RFLP. The control group consisted of 394 healthy volunteers. RESULTS: The TPMT*3A variant allele was found in 16 patients (15 TPMT*1/*3A, 1 TPMT*3A/*3A) and the TPMT*3C (A719G) allele in 1 patient. No TPMT*2 (G238C) or TPMT*3B (G460A) alleles were detected in the study group. TPMT*3A, TPMT*1 (wild-type), and TPMT*3C alleles were detected at frequencies of 3.94%, 95.81%, and 0.25%, respectively. The genotype and allele distributions were similar in the ALL and control groups. The 6-MP dose was reduced more frequently in patients with TPMT*3A and TPMT*3C alleles, compared with wild-type alleles (P = 0.042). Reductions because of leucopenia with respiratory tract infection, or because of leucopenia, anemia and/or thrombocytopenia were four (P = 0.007) and five (P = 0.03) times more common, respectively. The groups differed with regard to the rates of 6-MP dose reduction (P = 0.028). 6-MP was discontinued more often in patients with TPMT*3A and TPMT*3C alleles (14-fold) as a result of leucopenia, anemia, and/or thrombocytopenia (P = 0.004). CONCLUSIONS: The results indicate that TPMT genotype influences the safety and efficacy of ALL treatment and genotype information may therefore be useful for optimizing 6-MP therapy.
BACKGROUND:6-Mercaptopurine (6-MP) is used for the treatment of pediatric acute lymphoblastic leukemia (ALL). Mutations in the TPMT gene may influence the efficacy and safety of 6-MP treatment. This multicenter study investigated the association between TPMT genotype, 6-MP dose adjustments, and the incidence of adverse effects in patients. PROCEDURE: A total of 203 ALL children were genotyped using PCR/allele-specific amplification and PCR/RFLP. The control group consisted of 394 healthy volunteers. RESULTS: The TPMT*3A variant allele was found in 16 patients (15 TPMT*1/*3A, 1 TPMT*3A/*3A) and the TPMT*3C (A719G) allele in 1 patient. No TPMT*2 (G238C) or TPMT*3B (G460A) alleles were detected in the study group. TPMT*3A, TPMT*1 (wild-type), and TPMT*3C alleles were detected at frequencies of 3.94%, 95.81%, and 0.25%, respectively. The genotype and allele distributions were similar in the ALL and control groups. The 6-MP dose was reduced more frequently in patients with TPMT*3A and TPMT*3C alleles, compared with wild-type alleles (P = 0.042). Reductions because of leucopenia with respiratory tract infection, or because of leucopenia, anemia and/or thrombocytopenia were four (P = 0.007) and five (P = 0.03) times more common, respectively. The groups differed with regard to the rates of 6-MP dose reduction (P = 0.028). 6-MP was discontinued more often in patients with TPMT*3A and TPMT*3C alleles (14-fold) as a result of leucopenia, anemia, and/or thrombocytopenia (P = 0.004). CONCLUSIONS: The results indicate that TPMT genotype influences the safety and efficacy of ALL treatment and genotype information may therefore be useful for optimizing 6-MP therapy.
Authors: Y Tanaka; A Manabe; H Fukushima; R Suzuki; H Nakadate; K Kondoh; K Nakamura; K Koh; T Fukushima; M Tsuchida; K Koike; N Kiyokawa; E Noguchi; R Sumazaki; T Komiyama Journal: Pharmacogenomics J Date: 2014-11-18 Impact factor: 3.550
Authors: Marzena Skrzypczak-Zielinska; Pawel Borun; Katarzyna Milanowska; Ludwika Jakubowska-Burek; Oliwia Zakerska; Agnieszka Dobrowolska-Zachwieja; Andrzej Plawski; Ursula G Froster; Marlena Szalata; Ryszard Slomski Journal: Genet Test Mol Biomarkers Date: 2012-12-19
Authors: Mauricio J Farfan; Carolina Salas; Cristina Canales; Felipe Silva; Milena Villarroel; Katherine Kopp; Juan P Torres; María E Santolaya; Jorge Morales Journal: BMC Cancer Date: 2014-04-28 Impact factor: 4.430