Abstract：
BACKGROUND: 6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/μL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed \"skewed metabolism.\" Allopurinol may potentially correct skewed 6MP metabolism.
METHODS: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed.
RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001).
CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.
METHODS: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed.
RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001).
CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.
摘要：
背景：6-巯基嘌呤是小儿ALL维持治疗的基石。对6MP的响应通常由ANC确定。接受6MP时的治疗性ANC范围在500和1500/μL之间。除了所需的骨髓抑制，6MP与多种药物不良反应有关。增加6MP的剂量可以导致治疗性ANC值;然而，患者在获得治疗性骨髓抑制之前可能会出现不良反应，通常被认为是“扭曲的新陈代谢”。别嘌呤醇可能会纠正6MP代谢的偏斜。
方法：分析小儿ALL患者在维持治疗期间使用别嘌呤醇的情况。主要结果评估了别嘌呤醇开始之前和之后在治疗性ANC范围内花费的时间百分比。此外,别嘌呤醇起始前后6MMP：6TGN比率的差异，肝毒性的发生率，和复发率，进行了分析。
结果：95例患者被纳入分析。32例（34%）患者接受别嘌呤醇治疗。接受别嘌呤醇的患者和未接受别嘌呤醇的患者之间的基线人口统计学没有显着差异。当比较别嘌呤醇起始前后的ANC值时，观察到在治疗范围内花费的时间百分比的统计学显着增加(27%vs.43%；p=0.03）。此外,当比较别嘌呤醇起始前后的代谢物比率时，观察到6MMP：6TGN代谢物比值的统计学显着下降（86.7vs.3.6；p<.0001）。
结论：别嘌醇显著增加了治疗性ANC范围内的百分比时间，可以安全地用于显著降低6MMP:6TGN代谢物的比例，减轻6MMP的不良副作用，并优化与6TGN相关的抗白血病作用。
方法：分析小儿ALL患者在维持治疗期间使用别嘌呤醇的情况。主要结果评估了别嘌呤醇开始之前和之后在治疗性ANC范围内花费的时间百分比。此外,别嘌呤醇起始前后6MMP：6TGN比率的差异，肝毒性的发生率，和复发率，进行了分析。
结果：95例患者被纳入分析。32例（34%）患者接受别嘌呤醇治疗。接受别嘌呤醇的患者和未接受别嘌呤醇的患者之间的基线人口统计学没有显着差异。当比较别嘌呤醇起始前后的ANC值时，观察到在治疗范围内花费的时间百分比的统计学显着增加(27%vs.43%；p=0.03）。此外,当比较别嘌呤醇起始前后的代谢物比率时，观察到6MMP：6TGN代谢物比值的统计学显着下降（86.7vs.3.6；p<.0001）。
结论：别嘌醇显著增加了治疗性ANC范围内的百分比时间，可以安全地用于显著降低6MMP:6TGN代谢物的比例，减轻6MMP的不良副作用，并优化与6TGN相关的抗白血病作用。
