Severe unexpected impairment of renal methotrexate elimination after high-dose therapy

Even in patients with normal renal function, high-dose methotrexate therapy (HDMTX) may be followed by extremely prolonged MTX elimination though alkaline diuresis is performed correctly. By inquiry in Germany, Austria and Switzerland for HDMTX infusions with MTX plasma concentration 42 h after start of exposure (MTX-42) higher than 5 mu mol/l ( mu M), we analyzed data from 21 patients in whom impairment of renal methotrexate elimination had occurred at an age of 2 to 21 years. 18 patients had received 5 g/m super(2)/24 h, 3 had received 12 g/m super(2)/4 h. They presented with MTX-48 serum level between 1.7 and 1404 mu M.