Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity

Abstract

A 13 year-old girl with osteosarcoma and pulmonary tumor recurrence developed acute renal failure following high dose methotrexate (12 g/m(2)) therapy, she had previously tolerated high dose methotrexate and her renal and hepatic functions were normal. Briefly, 48 hours after beginning methotrexate infusion her methotrexate concentration and creatinine level were 1338.8 microM/L and 5.8 mg/dl, respectively. Grade IV oral mucositis and neutropenia with fever developed at 144 hours after MTX infusion. Hydration and alkalinization were continued and leucovorin rescue was intensified based on the plasma MTX concentrations. Plasma exchange was performed twice and hemodialysis 3 times without problems, but methotrexate and creatinine levels remained high, 91.9 microM/L, and 2.5 mg/dl, respectively. After 3 courses of hemodialysis carboxypeptidase-G2 (CPDG2) was administered at 50 U/kg, intravenously over 5 minutes. After 15 minutes of CPDG2 (Voraxaze) infusion, her plasma MTX concentration was 0.91 microM/L and no rebound elevation or side effects developed. Thirteen days post-MTX infusion her renal function had normalized. We report here our experience of a dramatic methotrexate level reduction caused by CPDG2 administration.

Keywords: Acute renal failure; Carboxypeptidase-G2; High dose methotrexate; Leucovorin.

Fig. 1

Schematic presentation of serum MTX and creatinine levels with time. Short arrows indicate days of plasma exchange, arrowheads indicate days of hemodialysis and the long arrow indicates the day of CPDG2 administration.