Italian expert consensus recommendations for the safe administration of high-dose methotrexate in children with cancer and for the use of glucarpidase to manage delayed methotrexate elimination and/or high-dose methotrexate-induced acute kidney injury

Background: High-dose methotrexate (HD-MTX) is used to treat various malignancies in adults and children. However, HD-MTX can lead to severe toxicity, which can require the use of glucarpidase, a recombinant enzyme that rapidly reduces MTX concentrations. Current guidelines, approximated from both adult and pediatric studies and established prescribing indications, do not provide detailed recommendations tailored to children to guide glucarpidase use in clinical practice. Methods: The current study used modified Delphi methodology to develop expert consensus recommendations for the safe administration of HD-MTX, and management of delayed MTX elimination (DME) and/or HD-MTX-induced acute kidney injury (AKI) in children with cancer. Consensus statements were developed by a multidisciplinary Scientific Board of eight Italian physicians, then circulated to an expert panel of 20 pediatric hematooncologists for voting. Expert panel members rated their level of agreement using a 5-point Likert scale; consensus was reached if >= 66.6 % of respondents indicated that they "agreed" or "strongly agreed" with each statement. Results: Of the 46 statements, 40 achieved consensus. Clinicians agreed that harmonized glucarpidase treatment guidelines are needed. Careful risk assessment performed by a multidisciplinary team should be established to ensure correct management of pediatric patients on relevant factors such as concomitant medications, monitoring of plasma MTX levels for DME, collection and processing of blood samples, monitoring of renal function for AKI prevention or management, and prompt availability of glucarpidase. Conclusions: These expert consensus recommendations will help pediatric hemato-oncologists to better deal with the various aspects associated with managing HD-MTX in general and with DME or AKI in particular.