Use of plasma exchange in methotrexate removal in a patient with osteosarcoma and acute renal insufficiency.

Acute renal failure induced by methotrexate (MTX) can be lethal because renal excretion of the drug can be delayed. Pre-existing renal impairment, abstention, or underdosage of folinic acid and inadequate hydration facilitate toxicity. The prolonged high serum levels of MTX result in severe mucositis and pancytopenia, but strategies useful to accelerate MTX removal have not been universally accepted. We report a case of a 13-year-old girl with osteosarcoma who was treated with high-dose MTX because of thoracic tumor recurrence. No side effects were observed after 2 cycles of high-dose MTX; however, after the third cycle there was a delayed MTX elimination followed by clinical toxicity. Forty hours post-MTX infusion the serum level of MTX was 5.39 x 10(-4) mol/L. Treatment was based on symptomatic measures, such as maintenance of an abundant and alkaline diuresis and parenteral administration of folinic acid. Concomitantly, plasma exchange was employed to accelerate MTX removal and reduce its toxicity. After 24 days, she was discharged from the hospital, and her renal function recovered gradually.

Cecyn KZ ，Lee J ，Oguro T ，Petrilli AS ，Bordin JO ... -  《AMERICAN JOURNAL OF HEMATOLOGY》

High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma.

High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2. The literature was reviewed for osteosarcoma trials, use of dialysis-based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate-release trial. Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade >/= 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods. HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently.

Widemann BC ，Balis FM ，Kempf-Bielack B ，Bielack S ，Pratt CB ，Ferrari S ，Bacci G ，Craft AW ，Adamson PC ... -  《CANCER》

Delayed methotrexate clearance in osteosarcoma patients treated with multiagent regimens of neoadjuvant chemotherapy.

Bacci G ，Ferrari S ，Longhi A ，Forni C ，Loro L ，Beghelli C ，Tremosini M ，Versari M ... -  《ONCOLOGY REPORTS》

Toxic encephalopathy and delayed MTX clearance after high-dose methotrexate therapy in a child homozygous for the MTHFR C677T polymorphism.

Müller J ，Kralovánszky J ，Adleff V ，Pap E ，Németh K ，Komlósi V ，Kovács G ... -  《ANTICANCER RESEARCH》

[Toxicosis of high-dose methotrexate (HD-MTX) for osteosarcoma, cured with treatment by leucovorin (LV) rescue and hemoperfusion--a case report].

Kobayashi H ，Morita T ，Hirata Y ，Kato T ，Okada Y ，Sato T ... -  《-》