Aim: To describe high-dose methotrexate toxicity management in a 28-year-old male of mixed ethnicity with MRD+ Early T-cell Precursor Acute Lymphoblastic Leukaemia admitted to a Brisbane hospital for ALL06 high-risk block 1 pre-allograft.
Method: A retrospective case review was conducted including examination of the patient’s parameters, treatment, and methotrexate toxicity management.
Results: The patient’s BSA was 2.48m2 with a height of 188cm and weight of 118kg. Methotrexate 5g/m2 was administered intravenously over 24 hours. The 24-hour level cleared (<150micromol/L), however the 36-hour level was raised at 15micromol/L (aim is <3micromol/L). An acute kidney injury developed with serum creatinine increasing from 73micromol/L to 172 micromol/L and 12kg weight gain in fluid. Administration of glucarpidase 50 units/kg intravenously 48 to 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) to minimise life-threatening toxicities. The 42-hour level was 11micromol/L (aim is <1micromol/L) and 48-hour level was 7.8micromol/L (aim is <0.4micromol/L). Calcium folinate rescue and sodium bicarbonate were administered as per protocol with diuretics required for fluid overload. The pharmacist liaised with a pharmacist at Peter MacCallum Cancer Centre (PMCC) in Melbourne regarding glucarpidase availability and dosing experience. The number of glucarpidase vials required exceeded the number available. The pharmacist discussed the availability, prior experience with a 2000 units capped dose, and pharmacokinetics with the haematology team and subsequently organised two 1000 units vials from PMCC. 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. Regain of normal renal function occurred within 4 weeks.
Conclusion: The glucarpidase 2000 units capped dose was deemed efficacious as part of methotrexate toxicity management.