Is hypoalbuminemia a risk factor for high-dose methotrexate toxicity in children with acute lymphoblastic leukemia?

backgroundRepeated high-dose methotrexate (HDMTX) is a critical component of contemporary childhood acute lymphoblastic leukemia (ALL) treatment regimens. Serum albumin is considered a carrier of methotrexate (MTX) in the blood. Hypoalbuminemia is not a rare finding in children with leukemia. This study aimed to investigate the relationship between pre-infusion serum albumin and possible HDMTX toxicities.

methodsThirty Egyptian children with ALL were consecutively enrolled in the study between May 2018 and July 2020. They were prospectively followed up while receiving HDMTX during the consolidation phase of the TOTAL study XV protocol. HDMTX was administered intravenously as a 24-h infusion every 2 weeks. Doses of 2.5 g/m

resultsThe patients' age ranged from 2.3 to 13.3 years at diagnosis, and most of them had B cell ALL (86.7%). Overall, 120 HDMTX cycles were analyzed, equally distributed between low and standard/high risk. Grade 3-4 anemia, grades 3-4 thrombocytopenia, febrile neutropenia, and oral mucositis were significantly more frequent in HDMTX cycles with pre-infusion hypoalbuminemia than those with normal pre-infusion albumin (p=0.003, p=0.007, p=0.006, and p=0.001, respectively). In addition, pre-infusion hypoalbuminemia was significantly associated with additional hospitalization due to HDMTX toxicity (p=0.031). Most HDMTX toxicities were comparable irrespective of the MTX dose. Oral mucositis was more frequently encountered in the 2.5 g/m

conclusionsSerum albumin levels should be checked before starting HDMTX cycles, especially in resource-limited settings where malnutrition is common, and serum MTX monitoring may not be available. Optimizing serum albumin levels before HDMTX may help decrease the possibility of HDMTX toxicities.