Strategies for Managing Toxicities With High‐Dose Methotrexate in Haematological Malignancies: Lessons From Clinical Cases

High-dose methotrexate (HDMTX) is a key component of induction therapy for a range of cancers, but can lead to serious adverse effects, including acute kidney injury (AKI). We report two cases of HDMTX use in haematological malignancies. Patient 1 was an 8-year-old girl with high-grade NHL. She received 3 courses of HDMTX (3 g/m²) without issue. For her 4th course, she developed AKI with creatinine peaking at 240 μmol/L after HDMTX administration. She required intensified hydration and antihypertensive therapy for fluid overload, received glucarpidase for delayed MTX clearance, required parenteral nutrition for mucositis and ultimately made a full recovery. Patient 2 was a 76-year-old man with primary central nervous system lymphoma. He underwent HDMTX treatment per the MARTA protocol with dose reductions due to renal impairment. He experienced delayed MTX clearance leading to fluid overload, acute liver injury, required prolonged diuretic and antibiotic therapy, and was hospitalised for 3 weeks before recovery. These cases emphasise the need for preemptive supportive care, including prehydration and folinic acid (leucovorin), careful monitoring and early intervention with glucarpidase in the event of toxicities.