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

Stefan Bielack; Christopher P Fox; Khê Hoang-Xuan; Ariadna Giró-Perafita; Carmelo Rizzari

doi:10.1002/hsr2.1749

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 Sci Rep. 2024 Jan 5;7(1):e1749. doi: 10.1002/hsr2.1749. eCollection 2024 Jan.

Authors

Stefan Bielack¹, Christopher P Fox², Khê Hoang-Xuan³, Ariadna Giró-Perafita⁴, Carmelo Rizzari^{5

6}

Affiliations

¹ Cooperative Osteosarcoma Study Group, Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart-Olgahospital Stuttgart Cancer Center Stuttgart Germany.
² School of Medicine University of Nottingham Nottingham UK.
³ IHU, Department of Neuro-oncology Mazarin, APHP Sorbonne University Paris France.
⁴ Omakase Consulting S.L. Barcelona Spain.
⁵ Unit of Pediatrics University of Milano-Bicocca Monza Italy.
⁶ Fondazione IRCCS San Gerardo dei Tintori Monza Italy.

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.

Keywords: MTX toxicity clinical management; acute kidney injury (AKI); epidemiology; high‐dose methotrexate (HDMTX); methotrexate delayed elimination.