Svasdisant Patpetra, Glomglao Waraporn, Siraprapapat Preeyanun, Inthararujikul Wiyakan, Tachavanich Kalaya, Boonthimat Chetsada, Ardsiri Sakkarin, Chansing Kochpinchon, Sriprach Suwimon, Tongsai Sasima, Sinlapamongkolkul Phakatip, Sanpakit Kleebsabai, Buaboonnam Jassada
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Research Department, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Mediterr J Hematol Infect Dis. 2023 Mar 1;15(1):e2023024. doi: 10.4084/MJHID.2023.024. eCollection 2023.
6-Mercaptopurine (6-MP), a thiopurine agent, is a essential medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase (), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites. Studies on and thiopurine-associated toxicities are scarce.
This study retrospectively investigated 1- to 15-year-old children with ALL who received 6-MP during the maintenance phase of treatment between 2000 and 2020. Toxicity during the first year of maintenance therapy and the mean dose of 6-MP were analyzed.
The 209 patients had a median age of 4.8 (0.3-14.8) years. Of these, 124 patients (59.3%) had wild-type , 73 patients (34.9%) had heterozygous (het), and 12 patients (5.7%) had homozygous (hom), with an allele frequency of 0.23. The incidence of neutropenia among polymorphisms did not significantly differ ( = 0.813). In patients harboring hom, transaminitis was more frequent than other polymorphisms but without a significant difference ( = 0.063). The mean dose of 6-MP for patients with hom was significantly lower than that for patients with het or wild-type ( = 0.016).
Hom had a higher incidence of transaminitis and required a significantly larger dose reduction of 6-MP than wild-type . Further study is warranted to elucidate the effects of polymorphisms on toxicity in patients with ALL treated with 6-MP.
6-巯基嘌呤（6-MP）是一种硫嘌呤类药物，是治疗儿童急性淋巴细胞白血病（ALL）的重要药物。然而，其导致的中性粒细胞减少和肝毒性副作用可能会中断治疗，导致不良预后。肌苷三磷酸焦磷酸酶（）是硫嘌呤途径中的一种酶，可能会阻止有毒硫嘌呤代谢物的积累。关于和硫嘌呤相关毒性的研究很少。
本研究回顾性调查了2000年至2020年期间在治疗维持阶段接受6-MP治疗的1至15岁ALL儿童。分析了维持治疗第一年的毒性和6-MP的平均剂量。
209例患者的中位年龄为4.8（0.3-14.8）岁。其中，124例患者（59.3%）为野生型，73例患者（34.9%）为杂合型（het），12例患者（5.7%）为纯合型（hom），等位基因频率为0.23。多态性中中性粒细胞减少的发生率无显著差异（=0.813）。在携带hom的患者中，转氨酶升高比其他多态性更常见，但无显著差异（=0.063）。携带hom的患者6-MP的平均剂量显著低于携带het或野生型的患者（=0.016）。
与野生型相比，hom转氨酶升高的发生率更高，6-MP的剂量需要显著降低。有必要进一步研究以阐明多态性对接受6-MP治疗的ALL患者毒性的影响。
