Publication: Effect of NUDT15 on incidence of neutropenia in children with acute lymphoblastic leukemia
Issued Date
2019-01-01
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ISSN
1442200X
13288067
13288067
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2-s2.0-85070782863
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Mahidol University
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SCOPUS
Bibliographic Citation
Pediatrics International. Vol.61, No.8 (2019), 754-758
Suggested Citation
Jassada Buaboonnam, Pariwan Sripatanatadasakul, Ajjima Treesucon, Waraporn Glomglao, Preeyanun Siraprapapat, Nattee Narkbunnam, Nassawee Vathana, Chayamon Takpradit, Kamon Phuakpet, Bunchoo Pongtanakul, Sasima Tongsai, Phakatip Sinlapamongkolkul, Kleebsabai Sanpakit Effect of NUDT15 on incidence of neutropenia in children with acute lymphoblastic leukemia. Pediatrics International. Vol.61, No.8 (2019), 754-758. doi:10.1111/ped.13905 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/52311
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Title
Effect of NUDT15 on incidence of neutropenia in children with acute lymphoblastic leukemia
Abstract
© 2019 Japan Pediatric Society Background: 6-Mercaptopurine (6-MP) is considered the backbone of therapy in the maintenance phase of acute lymphoblastic leukemia (ALL). Gene polymorphisms involved in thiopurine degradation are predictors of toxicity in patients treated with 6-MP. We investigated the effects of nucleoside diphosphate linked moiety X (nudix) type motif 15 (NUDT15) polymorphism NUDT15c.415C>T on neutropenia incidence, dose adjustment for 6-MP, and survival rates in Thai children with ALL. Methods: Children diagnosed with ALL who received 6-MP in the maintenance phase of treatment, in 2005–2016, were retrospectively enrolled. Results: The subjects consisted of 102 patients (median age, 5.2 years; 58 boys). On genetic testing 78, 22, and two patients were normal (CC), heterozygous (CT), and homozygous (TT), respectively. The incidence of neutropenia at 3 months was significantly higher in the CT/TT than CC polymorphism groups (OR, 12; 95%CI: 3.781–38.085, P < 0.001). The mean dose of 6-MP at 3, 6, and 12 months was significantly lower in the CT/TT versus the CC group (P < 0.001). The 5 year overall survival (OS) rate for CC was 80.4%, and for CT/TT, 95.5% (P = 0.34). The 5 year event-free survival (EFS) for CC and CT/TT was 75.1% and 85.7%, respectively (P = 0.17). After adjusted risk classification, no significant differences were observed for OS or EFS between the CC and CT/TT groups. Conclusion: Patients harboring the CT/TT polymorphism of NUDT15 had a significantly higher incidence of neutropenia during the first 3 months of maintenance, resulting in significantly lower doses of 6-MP.