Department of Pediatrics, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas, USA.
Pediatr Blood Cancer. 2025 Jan;72(1):e31377. doi: 10.1002/pbc.31377. Epub 2024 Oct 10.
Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.
This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered a proxy for constipation. Multilevel logistic regression models evaluated associations between clinical factors and delayed HD-MTX excretion to account for multiple MTX cycles per individual.
A total of 533 eligible patients received 1875 HD-MTX infusions. Patients were mostly male (59.8%), Hispanic (56.7%), with a median age of 9.5 years. Delayed excretion was observed following 42.7% of HD-MTX infusions, and patients received two or more laxative doses during 19.9% of infusions. Independent of other factors, individuals who received two or more laxative doses were nearly 60% (odds ratio 1.58; 95% confidence interval: 1.19-2.09; p = .002) more likely to experience delayed excretion compared to those receiving fewer than two laxative doses.
Receipt of at least two laxative doses was independently associated with delayed methotrexate excretion in pediatric patients with ALL. Future prospective studies are needed to confirm the secondary effects of constipation and confirm the association with constipation and identify clinical benefits that optimize drug excretion.
大剂量甲氨蝶呤（HD-MTX）在小儿急性淋巴细胞白血病（ALL）中的排泄延迟可导致严重的发病率。虽然甲氨蝶呤主要通过肾脏排泄，但 HD-MTX 可能会超过肾脏排泄能力，并增加对粪便排泄的依赖。本研究评估了便秘时使用泻药与 HD-MTX 排泄延迟之间的关系。
这项多中心病历回顾性研究纳入了 2010 年至 2020 年间接受 HD-MTX（5 g/m2）治疗的 ALL 患儿。血清 MTX 浓度在 48 小时仍大于 0.4 μM 被定义为排泄延迟。我们确定了每次 HD-MTX 输注后泻药的使用情况，两次或以上的剂量被认为是便秘的替代指标。多水平逻辑回归模型评估了个体中多个 MTX 周期内的临床因素与 HD-MTX 排泄延迟之间的关联。
共有 533 名符合条件的患者接受了 1875 次 HD-MTX 输注。患者主要为男性（59.8%）、西班牙裔（56.7%），中位年龄为 9.5 岁。42.7%的 HD-MTX 输注后出现排泄延迟，19.9%的输注中患者接受了两次或更多次泻药剂量。在其他因素独立的情况下，与接受少于两次泻药剂量的患者相比，接受两次或更多次泻药剂量的个体发生排泄延迟的可能性高近 60%（比值比 1.58；95%置信区间：1.19-2.09；p=0.002）。
在接受 ALL 治疗的小儿患者中，至少接受两次泻药剂量与 MTX 排泄延迟独立相关。需要进一步前瞻性研究来确认便秘的继发效应，并确认与便秘的关联，以及确定优化药物排泄的临床益处。
