Section of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescence Medicine, Aalborg University Hospital, Reberbansgade, 9000, Aalborg, Denmark.
Childhood Cancer and Research Unit, University Children's Hospital, Lund, Sweden.
Cancer Chemother Pharmacol. 2024 Dec;94(6):775-785. doi: 10.1007/s00280-024-04713-0. Epub 2024 Sep 21.
High-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor.
To examine the impact of serum albumin we reviewed 325 HDMTX 5 g/m2 courses in a cohort of 51 children treated on the NOPHO ALL 2008 protocol, dividing the courses into four groups with different levels of baseline albumin (A < 25 g/L, B 25-29 g/L, C 30-34 g/L and D ≥ 35 g/L).
Hypoalbuminemia was present in 51% of the courses, mostly in the early phases of chemotherapy while asparaginase therapy is ongoing, and especially if given less than 2 weeks after a dose (78%). Hypoalbuminemia had a significant impact on the end-of-infusion serum MTX, depending on the degree of hypoalbuminemia: MTX > 150 µM was seen in 37%, 32%, 20% and 8% in groups A to D. Serum albumin < 30 g/L was significantly associated with low MTX clearance < 10 L/h/1.73m2 (78% vs. 36%) and high AUC ≥ 1000 µM*h (44% vs. 31%). The frequency of rising creatinine or prolonged elimination was not increased, but the risk of stomatitis was significantly higher (42% vs. 19%).
Low serum albumin is caused by concurrent asparaginase therapy and has a clinically significant impact on MTX disposition. Guidelines for administering HDMTX may need adjustment if serum albumin < 30 g/L, and, if possible, HDMTX courses should not be scheduled soon after asparaginase doses.
高剂量甲氨蝶呤（HDMTX）疗法是急性淋巴细胞白血病（ALL）治疗方案的重要组成部分。该方案与肾损伤、清除延迟和全身毒性增加的风险相关。最近，低白蛋白血症被认为是另一个危险因素。
为了研究血清白蛋白的影响，我们回顾了在 NOPHO ALL 2008 方案中接受治疗的 51 名儿童的 325 例 5 g/m2 HDMTX 疗程，将疗程分为白蛋白基线水平不同的 4 组（A < 25 g/L、B 25-29 g/L、C 30-34 g/L 和 D ≥ 35 g/L）。
51%的疗程存在低白蛋白血症，主要发生在化疗早期伴门冬酰胺酶治疗期间，尤其是在剂量后不到 2 周时（78%）。低白蛋白血症对输注结束时的血清 MTX 有显著影响，取决于低白蛋白血症的程度：A 至 D 组中分别有 37%、32%、20%和 8%的患者出现 MTX > 150 µM。血清白蛋白 < 30 g/L 与低 MTX 清除率 < 10 L/h/1.73m2（78%比 36%）和 AUC≥1000 µM*h（44%比 31%）显著相关。肌酐升高或清除时间延长的频率没有增加，但口腔炎的风险显著更高（42%比 19%）。
低血清白蛋白是由同时使用门冬酰胺酶引起的，对 MTX 分布有临床显著影响。如果血清白蛋白 < 30 g/L，可能需要调整 HDMTX 的给药指南，如果可能，HDMTX 疗程不应在门冬酰胺酶剂量后不久安排。
