Life-threatening complications after high-dose methotrexate and the benefits of glucarpidase as salvage therapy: a cohort study of 468 patients

Chloé Medranoa, Lucie Obericb, Florent Puissetc, Christian Recherb, Delphine Larrieu-Cirond, Loïc Ysebaertb, Caroline Protinb, Muriel Picarde, Sophie Perriatc, Etienne Chatelutc , Sarah Bertolib, Françoise Huguetb, Suzanne Tavitianb & Stanislas Faguerafg*a Département de Néphrologie et Transplantation d’organes – Unité de Réanimation, Centre Hospitalier Universitaire de Toulouse, French Intensive Care Renal Network, Toulouse, Franceb Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse – Oncopôle, Université Toulouse III Paul Sabatier, Toulouse, Francec Laboratoire de Pharmacologie, Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse - Oncopôle, and Centre de Recherche sur la Cancer de Toulouse, INSERM UMR-1037, Toulouse, Franced Service de Neurologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, Francee Département d’anesthésie et de réanimation, Réanimation Médicale, Institut Universitaire du Cancer de Toulouse – Oncopole, Centre Hospitalier Universitaire de Toulouse, Toulouse, Francef INSERM U1048 (Institut des Maladies Métaboliques et Cardiovasculaires, équipe 12), Hôpital Rangueil, Toulouse, Franceg Université Paul Sabatier – Toulouse III, Toulouse, FranceSupplemental data for this article can be accessed here.CONTACT Stanislas Faguer stanislas.faguer@inserm.fr Département de Néphrologie et Transplantation d’Organes, Unité de Réanimation, INSERM U1048 (équipe 12, I2MC), Hôpital Rangueil, 1, avenue Jean Poulhes, Toulouse Cedex 31059, FranceAbstractThe aims of this study were to characterize the incidence and outcomes of severe toxicities following the administration of high-dose methotrexate (HD-MTX; ≥1 g/m2). Among the 468 patients included in the study, 69 (14.9%) developed at least one episode of acute kidney injury (AKI; 138/1264 HD-MTX administrations), including 34 (7.2%) who developed KDIGO stage 2-3 AKI. The three baseline factors independently associated with the risk of developing AKI were age, body mass index and a diagnosis of acute lymphoblastic leukemia. Higher plasma MTX concentration was associated with AKI and extra-renal toxicities. Notwithstanding potentially confounding factors, most patients with AKI who received glucarpidase (n = 41) developed extra-renal toxicity (leading to the death of two patients) despite early administration. Thus, severe toxicity and death can occur whether or not glucarpidase is administered, which confirms the need for further interventional studies to provide greater precision on its role in the management of HD-MTX toxicity.