CN-10SHOULD CARBOXYPEPTIDASE BE USED MORE OFTEN SINCE ITS FDA APPROVAL? - A CASE OF SUCCESSFUL METHOTREXATE TOXICITY RESCUE IN A PATIENT WITH NEUROLYMPHOMATOSIS.

BACKGROUND: High-dose methotrexate (HDMTX)-induced nephrotoxicity is rare and can be prevented with hydration, urine alkalinization, and leucovorin. When hemodialysis is used, rebound in MTX concentrations can occur after stopping dialysis. Carboxypeptidase metabolizes MTX to inactive metabolites and provides an alternative route of elimination, resulting in >98% decrease in MTX concentrations. METHODS: A 62 year-old woman with a history of Mullerian cancer, previously treated with resection and chemotherapy, presented with confusion, leg weakness, and incontinence. MRI of neuraxis revealed leptomeningeal enhancement in the cervicothoracic cord and cauda equina and T2/FLAIR hyperintensity in the cerebral hemispheric sulci. PET-CT showed FDG avidity in the thoracic cord, cauda equina, and right abdominal wall. CSF flow cytometry revealed abnormal mature B cells, concerning for diffuse large B-cell lymphoma. The presumptive diagnosis was neurolymphomatosis. Dexamethasone and spinal irradiation were initiated. Biopsy of the FDG-avid abdominal nodule was considered but it disappeared on repeat imaging. Cycle 1 of HDMTX and rituximab was complicated by pancytopenia. One month later, the patient re-presented with confusion and required a ventriculoperitoneal shunt for acute communicating hydrocephalus. During cycle 2 of HDMTX, she developed acute kidney injury, transaminitis, and worsening mentation, concerning for MTX toxicity. MTX level 21 hours after administration was 410 micromol/L. Hemodialysis and administration of carboxypeptidase resulted in marked improvement of MTX levels, hepatorenal function, and clinical status. CONCLUSIONS: This is an unusual case of neurolymphomatosis in an immunocompromised patient with previous Mullerian cancer. The etiology of MTX toxicity remains unclear although concomitant UTI and sepsis in our patient was likely contributory. Prompt use of carboxypeptidase eliminated MTX and prevented severe hepatic and hematologic toxicity. Carboxypeptidase is now FDA-approved and should be considered in patients with MTX toxicity who do not respond to standard rescue protocols. Use can be cost-limited as treatment of an average patient may exceed $100,000.