A Delphi study to determine the epidemiology and clinical management of patients treated with HDMTX who develop methotrexate (MTX) delayed elimination in France, Germany, Italy, and the UK

Bielack, Stefan; Fox, Christopher P.; Hoang‐Xuan, Khê; Giró‐Perafita, Ariadna; Rizzari, Carmelo

Abstract

Introduction: High‐dose methotrexate (HDMTX) is administered for the treatment of some malignancies. Serious complications after the administration of HDMTX are rare, but occasionally MTX may precipitate in the renal tubes causing a delayed elimination leading to renal, multiorgan toxicities and to life‐threatening complications. This study aims to estimate the incidence and clinical management of delayed MTX elimination in France, Germany, Italy, and the UK. Methods: Twelve haemato‐oncology and pediatric oncology clinical experts from leading European hospitals participated in the study. A two‐round Delphi methodology was used to gather data on different variables relevant to evaluate the HDMTX induced‐toxicity impact. For quantitative data, median and interquartile ranges were calculated. Data on prevalence was calculated considering the number of patients in each hospital and the population they cover, and then, extrapolated to the country population. Results: The total number of patients treated annually with HDMTX in France, Germany, Italy, and the UK is estimated in 7155. Of these, 16% are estimated to develop delayed MTX elimination and around 9% may develop HDMTX‐induced acute kidney injury (AKI). Leucovorin, hyperhydration and urine alkalinization are applied to prevent MTX toxicity and precipitation whilst glucarpidase, hemofiltration and hemodialysis are being used for persisting toxic MTX serum levels. Grade 3 systemic toxicities are common in these patients, hematologic and gastrointestinal being the most common ones. Conclusions: This report provides expert clinical practice experience and opinion of the incidence and management of HDMTX‐delayed elimination in France, Germany, Italy and the UK, thereby contributing to the evidence available on this relevant medical condition which can be life‐threatening.

Citation

Bielack, S., Fox, C. P., Hoang‐Xuan, K., Giró‐Perafita, A., & Rizzari, C. (2024). A Delphi study to determine the epidemiology and clinical management of patients treated with HDMTX who develop methotrexate (MTX) delayed elimination in France, Germany, Italy, and the UK. Health Science Reports, 7(1), Article e1749. https://doi.org/10.1002/hsr2.1749

• Journal Article Type: Article
• Acceptance Date: Nov 21, 2023
• Online Publication Date: Jan 5, 2024
• Publication Date: 2024-01
• Deposit Date: Feb 5, 2024
• Publicly Available Date: Feb 5, 2024
• Journal: Health Science Reports
• Electronic ISSN: 2398-8835
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 1
• Article Number: e1749
• DOI: https://doi.org/10.1002/hsr2.1749
• Keywords: MTX toxicity clinical management, methotrexate delayed elimination, epidemiology, high‐dose methotrexate (HDMTX), acute kidney injury (AKI)
• Public URL: https://nottingham-repository.worktribe.com/output/29539202
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1749
• Additional Information: Received: 2023-02-26; Accepted: 2023-11-21; Published: 2024-01-05