Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use

Abstract

The successful resumption of high-dose methotrexate in a 13-year-old boy with recurrent anaplastic large-cell lymphoma (ALCL) who suffered renal dysfunction after a 24-hour infusion of high-dose methotrexate and required treatment with carboxypeptidase G(2) (CPDG(2) ) is described. A 13-year-old boy who had been diagnosed in 2001 with stage I ALCL was admitted to the hospital in February 2005 after he developed a smaller left axillary mass in the area of his original mass. Recurrent ALCL was diagnosed, and treatments were initiated based on branch K3 of the protocol published in the non-Hodgkin's lymphoma-Berlin-Frankfurt-Münster (NHL-BFM) trial 90. In the NHL-BFM 90 protocol, all AA and BB courses include high-dose methotrexate therapy, which consists of aggressive alkalinized hydration, methotrexate 5 g/m(2) given as an i.v. infusion over 24 hours, and leucovorin rescue. During course BB2, the boy's serum methotrexate values exceeded NHL-BFM goals at 36, 42, and 48 hours. Because the patient's elimination of methotrexate remained slow and his serum creatinine level remained above normal limits, CPDG(2) was obtained for the treatment of methotrexate toxicity. The patient tolerated the CPDG(2) without adverse effects, and the patient's serum methotrexate concentration decreased from 14.47 to 0.66 microM. The patient went on to complete six courses based on the protocol. High-dose methotrexate was resumed at 50% then 100% of the original dose. He is currently in remission on maintenance therapy. A 13-year-old boy with recurrent ALCL had methotrexate-induced nephrotoxicity following high-dose methotrexate. The resultant delayed methotrexate clearance required the standard therapies as well as use of investigational CPDG(2). High-dose methotrexate was successfully resumed.