(P 151) CLINICAL PRESENTATION OF OSTEOSARCOMA PATIENTS WITH ACUTE METHOTREXATE TOXICITY TREATED WITH GLUCARPIDASE

Objective: High dose methotrexate is commonly used in treatment protocols for osteosarcoma. Acute methotrexate toxicity is a rare event but can result in multiorgan damage. In 2012, glucarpidase was approved for treatment of toxic methotrexate levels and in 2018 a consensus guideline was created for use of glucarpidase [1]. There have been multiple individual cases describing the clinical presentation of methotrexate toxicity, but no larger case series that demonstrate a clinical pattern. Our objective is to describe the prevalence of early clinical signs and symptoms in patients with methotrexate toxicity requiring glucarpidase to help providers identify these patients early.

Methods: Single institution retrospective record review of all solid tumor patients who received glucarpidase for methotrexate toxicity from 2006 to present from a single institution. 14 patients with osteosarcoma were identified. One patient was excluded because of being transferred to our facility after administration of methotrexate. Data collected on the remaining 13 patients included age, gender, dose of methotrexate received, methotrexate and creatinine levels at 24, 48, 72, 96, and 120 hours, timing and value of peak methotrexate and creatinine level, presenting signs and symptoms, and timing of these presenting symptoms. The data regarding signs and symptoms were collected from review of nursing documentation as well as physician documentation in the chart.

Results: The peak methotrexate level was at a mean of 795 umol/L at 16 hours and the peak creatinine level was 1.98 mg/dL at 50 hours (baseline creatinine was mean of 0.54 mg/dL). The mean 24-hour methotrexate level was 330 umol/L. In terms of symptoms, 5 patients were found to have abdominal pain, 3 had back pain, 3 had extremity pain, and 10 had nausea/vomiting. The mean time to symptom onset from start of methotrexate infusion was 10.5 hours for abdominal pain, 16 hours for back pain, 15 hours for extremity pain. Nausea and vomiting was most frequently observed during the time of methotrexate infusion.

Conclusion: Methotrexate toxicity is known to result in serious organ toxicity. Peak toxic methotrexate levels are seen early after administration, but peak creatinine values lag behind. Patients who present with early symptoms, such as severe early nausea/vomiting, abdominal pain, back pain, and extremity pain, may have acute methotrexate toxicity and should be monitored closely. Because there can often be a delay in administering glucarpidase, it may be prudent that patients with these symptoms get evaluated promptly with a higher suspicion for possible methotrexate toxicity.