接受急性淋巴细胞白血病（ALL）维持治疗的儿童中，抗代谢药物剂量强度（DI）与不良事件之间的关系仍不清楚，特别是在抗代谢药物依从性的情况下。使用 COG-AALL03N1 数据，我们检查了前四个研究月内的高 DI 与 (i) 随后两个研究月内与治疗相关的毒性之间的关联； (ii) 复发风险。患者被分类为高 DI 表型（前 4 个月研究期间 6-巯基嘌呤 [6-MP] 或甲氨蝶呤 [MTX] DI ≥110%，或研究入组时 6-MPDI 或 MTXDI 100%-110%，且≥四个研究月内增加 25%）和正常 DI 表型（所有其他）。仅纳入野生型 TPMT 和 NUDT15 的患者。 63.7% 的研究参与者可获得 6-MP 依从性数据，并用于分层为依从性（中位依从性≥85%）和非依从性（中位依从性<85%）参与者。针对社会人口统计学和临床​​预测因素调整了多变量分析。在 644 名患者中，29.3% 暴露于高DI。在整个队列中，高 DI 与血液学毒性的几率增加 2.1 倍（95% CI=1.4-3.1；参考：正常 DI），而在坚持者中则增加 2.9 倍（95% CI=1.6-5.1）；非依从者之间的几率相当（2.1 倍，95%CI=0.4-10.1）。虽然高 DI 与整个队列中的复发无关（调整后的风险比 [aHR]=1.4，95%CI=0.8- 2.4），它与依从性参与者（aHR=2.4，95%CI=1.0-5.5）的更大复发风险相关，但与非依从性参与者（aHR=0.9，95%CI=0.2-3.8）无关。在评估对处方治疗的依从性后，应谨慎地在 ALL 维持治疗期间将剂量递增至高于方案剂量。版权所有 © 2024 美国血液学会。

The association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in context of antimetabolite adherence. Using COG-AALL03N1 data, we examined the association between high DI during the first four study months and (i) treatment-related toxicities during the subsequent two study months; and (ii) relapse risk. Patients were classified into a high DI phenotype (either 6-mercaptopurine [6-MP] or methotrexate [MTX] DI ≥110% during the first four study months, or 6-MPDI or MTXDI 100%-110% at study enrollment and ≥25% increase over the four study months) and normal DI phenotype (all others). Only patients with wildtype TPMT and NUDT15 were included. 6-MP adherence data were available for 63.7% of study participants and used to stratify as adherent (median adherence ≥85%) and non-adherent (median adherence <85%) participants. Multivariable analyses were adjusted for sociodemographic and clinical prognosticators. Of the 644 patients, 29.3% were exposed to high DI. High DI was associated with a 2.1-fold greater odds of hematologic toxicity (95%CI=1.4-3.1; reference: normal DI) in the entire cohort and 2.9-fold higher among adherers (95%CI=1.6-5.1); odds were comparable among non-adherers (2.1-fold, 95%CI=0.4-10.1).. While high DI was not associated with relapse in the entire cohort (adjusted hazard ratio [aHR]=1.4, 95%CI=0.8-2.4), it was associated with a greater hazard of relapse among adherent participants (aHR=2.4, 95%CI=1.0-5.5) but not among non-adherent participants (aHR=0.9, 95%CI=0.2-3.8). Dose escalation above protocol doses during maintenance therapy for ALL should be done cautiously after assessing adherence to prescribed therapy.Copyright © 2024 American Society of Hematology.