OBJECTIVES: No studies have been published about the impact of methotrexate-related toxicity in Spain. We used the Delphi technique to estimate the incidence and clinical management of patients receiving high-dose methotrexate (HDMTX) as part of their chemotherapy treatment who develop methotrexate toxicity due to delayed methotrexate elimination.

METHODS: Medical experts on the haemato-oncology and paediatric oncology field directly involved in the management of HDMTX treated patients were selected from leading Spanish hospitals and from hospitals with experience on the use of glucarpidase (n=10). Two-round Delphi study using online questionnaire was performed to reach consensus. The questionnaire was developed based on national and international clinical guidelines and published evidence on HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile range was calculated.

RESULTS: Out of 1.475 patients treated annually with HDMTX in Spain, 11.6% are estimated to develop acute kidney injury (12,9% adults; 9,5% paediatric). Mortality was estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (9/10) to monitor MTX serum. All experts would use high leucovorin doses and increased supportive care as first line of treatment. If MTX toxicity persists, treatments available in experts’ hospitals are haemodialysis (9/10), glucarpidase (6/10), hemofiltration (6/10) and exchange transfusion/plasma exchange (5/10). In the hospitals where glucarpidase is available, 63% [5-100] of patients would receive it. Most prevalent Grade 3 or above non-renal systemic toxicities are haematologic toxicity and mucositis (21-40% of patients). Approximately, 5% [1-13] of patients with HDMTX-induced AKI would require intensive care.

CONCLUSIONS: These results are the first evidence of HDMTX-induced AKI in Spain. Incidence and mortality are in line with previous studies from other countries (incidence 2-12%, mortality 4-6%). Although HPLC is a more accurate method, immuno-enzymatic assay is the most used in Spanish hospitals to monitor MTX serum levels. Further observational studies would be needed.