Purpose: To describe a case series of three patients who required glucarpidase administration after developing high-dose methotrexate (HDMTX) toxicity following treatment for acute lymphoblastic leukaemia.
Sample and setting: Patients were administered treatment at a quaternary metropolitan hospital in Brisbane.
Procedures: A retrospective case review was conducted including examination of the patient’s parameters, treatment, and HDMTX management.
Results: Patients A, B and C had a body surface area of 2.48m2, 2.34m2, and 2.02m2, respectively. Methotrexate 5g/m2 was administered intravenously over 24 hours for all 3 patients. An acute kidney injury developed for all 3 patients with serum creatinine increasing from 79micromol/L to 172micromol/L for patient A, 76micromol/L to 130micromol/L for patient B and 67 micromol/L to 117micromol/L for patient C. Forty-two hour methotrexate levels returned as 11, 13, 8.6 (<1micromol/L) for patient A, B and C, respectively. Serum creatinine peaked at 250, 164, 125micromol/L for patients A, B and C, respectively. Administration of glucarpidase 50units/kilogram intravenously within 60 hours post-methotrexate is recommended if serum creatinine is >1.5x upper limit of normal (or ≥2x patient baseline) with elevated methotrexate level. Glucarpidase converts extracellular methotrexate into its inactive metabolites, glutamate and DAMPA (4-deoxy-4-amino-N10-methylpteroic acid). Calcium folinate rescue and sodium bicarbonate were administered as per protocol with diuretics required for fluid overload. Two thousand international units were ordered and administered to all three patients within 56 hours of MTX starting. There was a significant reduction in methotrexate levels following glucarpidase administration; however, level interpretation was difficult due to both DAMPA cross-reactivity with the immunoassay and fluid shifts. It took an average of 12 days for methotrexate levels to fall <0.1micromol/L. Regain of normal renal function varied across each patient
Conclusion and clinical implications: The glucarpidase 2000 units capped dose was deemed efficacious as part of methotrexate toxicity management for all three patients.