Abstract: PUB636
The Use of Early Continuous Venovenous Haemofiltration and Glucarpidase Therapy in the Management of Methotrexate Toxicity
Session Information
Category: Trainee Case Report
- 1500 Onco-Nephrology
Author
- D'Arcy, Suzanne, Cork University Hospital, Cork, Ireland
Introduction
Methotrexate (MTX) is a widely utilised anti-metabolite, however its use in extremely high doses (greater than 500mg/m2) is commonly the preserve of the oncologist. At toxic levels, its side effects include severe myelosuppression and acute kidney injury. MTX toxicity i.e; levels >1umol/L at 48 hours, are commonly observed, normally in the setting of impaired renal function. This case demonstrates the utility of combination therapy of early CVVH, leucovorin and glucarpidase therapy in the successful treatment of a patient with MTX toxicity.
Case Description
The 79 year old patient was diagnosed with stage 4 Non-Hodgkins Lymphoma and was commenced on R-CHOP therapy. He was admitted for iv MTX as an adjunct to his chemotherapy. At this time, his renal function was normal. He proceeded to treatment with iv isotonic bicarbonate and high-dose leucovorin. During his inpatient stay, he sustained a pre renal kidney injury.
He required transfer to ICU for non invasive ventilatory support due to respiratory sepsis. At 48 hours post infusion his MTX levels were 19.61 umol/L. CVVH was started at a dose of 30 ml/kg/hr, within 52 hours of administration of MTX. The patient did not become oliguric and his peak creatinine was 1.89mg/dL. His MTX levels continued to fall over subsequent days. At hour 58 post infusion, the patient was administered glucarpidase, a recombinant bacterial enzyme which cleaves MTX into two non-cytotoxic metabolites. Of note is that immunoassay does not differentiate between the levels of active MTX and inactive metabolites. Due to this, CVVH was continued until MTX levels were below 1 umol/L. The patient was transferred from ICU after 9 days and was discharged following 29 days of admission with restored renal function.
Discussion
Previous cases reports have demonstrated the usage of CVVH in MTX toxicity when absolute indications arise for renal replacement therapy. However, here, CVVH was commenced with the express intent of reducing absolute serum MTX levels. The patient did not develop any haemorrhagic or infective complications of myelosuppression and continued to improve until his successful discharge after 29 days. This case demonstrates that combination therapy of early CVVH with glucarpidase therapy in conjunction with high dose leucovorin can be associated with promising outcomes in terms of therapy of MTX toxicity.