Fixed-dose glucarpidase use for high-dose methotrexate toxicity: A case series in Acute Lymphoblastic Leukemia

IntroductionGlucarpidase 50 units per kilogram (units/kg) intravenously is indicated for high-dose methotrexate (HDMTX) toxicity, however lower doses are often used.Case seriesThree patients with Acute Lymphoblastic Leukemia were administered HDMTX 5g/m² intravenously over 24 h, developed toxicity, and required glucarpidase. Retrospective data collection included methotrexate (MTX) and creatinine levels and toxicity management. An acute kidney injury developed for all patients with serum creatinine increasing from 79 micromol/L to 172 micromol/L for patient A, 76 micromol/L to 130 micromol/L for patient B, and 67 micromol/L to 117 micromol/L for patient C. Forty-two hour MTX levels returned as 11, 13, 8.6 micromol/L (target is <1 micromol/L) and serum creatinine peaked at 250, 164, and 125 micromol/L for patients A, B, and C, respectively.Management and outcomeCalcium folinate, fluids, sodium bicarbonate, and diuretics were administered as indicated. All patients received glucarpidase 2000 units within 56 h of HDMTX commencing. MTX levels took an average of 12 days to fall to <0.1 micromol/L. Regain of normal renal function post-glucarpidase took 25 and 8 days for patients A and C respectively; patient B was lost to follow up.DiscussionWith evidence of efficacious glucarpidase dosing lower than 50 units/kg, including in this case series (2000 units), combined with its pharmacokinetic properties, 1000 units should be considered for adult patients less than 200 kilograms with a supratherapeutic MTX level of 200 micromol/L or less, from 24 h or 36 h (depending on the protocol used) to 60 h post-HDMTX commencement. This necessitates one 1000 units vial, reducing cost and potentially improving access.