Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia: A Danish population-based study

Research output: Contribution to journalArticle

Bibtex

@article{9eedf70b17314974aa1f99226ce9076e,
title = "Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia: A Danish population-based study",
abstract = "Background: Severely delayed elimination of methotrexate (MTX) is difficult to predict in patients treated with high-dose MTX (HD-MTX), but it may cause life-threatening toxicity. It has not been defined how an increase in plasma creatinine can be best used as a predictor for severely delayed MTX elimination, thus providing a guide for therapeutic interventions to minimize renal toxicity. Methods: Pharmacokinetic data were retrospectively collected on 218 Danish children with acute lymphoblastic leukemia treated with HD-MTX 5 or 8 g/m 2 on the NOPHO2000 protocol. Moderately delayed MTX elimination was defined as 42-hour plasma MTX ≥ 4.0–9.9 μM, and severely delayed elimination was defined as 42-hour plasma MTX ≥ 10 μM. Results: Median 42-hour plasma MTX was 0.61 μM (interquartile range, 0.4–1.06 μM). Of 1295 MTX infusions with 5 g/m 2 (n = 140 patients) or 8 g/m 2 (n = 78 patients), 5.1{\%} were severely (1.5{\%}) or moderately (3.6{\%}) delayed. The risk of having delayed elimination was highest in the first of eight infusions with MTX 5 g/m² (7.4{\%} vs 0.0 to 4.1{\%} for subsequent MTX infusions) (P < 0.02). A 25 μM increase or a 1.5-fold increase in plasma creatinine within 36 hours from start of the MTX infusion had a sensitivity of 92{\%} (95{\%} CI, 82{\%}–97{\%}) and a specificity of 85{\%} (95{\%} CI, 83{\%}–87{\%}) for predicting 42-hour MTX ≥4.0 μM. Conclusions: A 25 μM increase or a 1.5-fold in plasma creatinine within 36 hours after start of an HD-MTX infusion can predict delayed MTX elimination, thus allowing intensification of hydration and alkalization to avoid further renal toxicity and promote the elimination of MTX.",
keywords = "acute leukemias, ALL, chemotherapy, methotrexate, support care cancer pharmacology",
author = "Diana Schmidt and Kim Kristensen and Henrik Schroeder and Wehner, {Peder Skov} and Steen Rosth{\o}j and Jesper Heldrup and Linn Damsgaard and Kjeld Schmiegelow and Mikkelsen, {Torben Stamm}",
year = "2019",
doi = "10.1002/pbc.27637",
language = "English",
volume = "2019",
journal = "Pediatric Blood & Cancer",
issn = "1545-5017",
publisher = "John Wiley and Sons Inc.",

}