A 4-year-old boy was diagnosed as having osteosarcoma of the left proximal humerus. His laboratory test results, including the serum creatinine and creatinine clearance, were all in the normal range. His first course of HD MTX was administered at 12 g/m². One hour before MTX infusion, he was intravenously hydrated with 250 mL/m² of 5% glucose together with containing 100 mol/L NaHCO₃ and 20 mL KCl solution. The MTX was dissolved in 500 mL of D₅W and infused over 4 hours. After this MTX infusion, he was hydrated with the same fluid to a total of 1,500 mL/m² during the first 24 hours. His 4-hour MTX level was 1,522 µmol/L, and he suffered from mild nausea. His oral intake was moderate and the urine volume was maintained at above 1,750 mL/day. The following day, he had gained 1.2 kg in weight (range, 19.4 to 20.6 kg), and he complained of abdominal pain, nausea and vomiting. His 24-hour MTX level was 781 µmol/L, and thus, leucovorin was immediately escalated to 1,000 mg/m² and administered every 3 hours. His serum creatinine level increased up to 2 mg/dL, but his urine output was maintained at above 50 mL/m²/hr without diuretics. He suffered oral mucositis (grade III), and yet he did not experience any diarrhea, fever or leukopenia. Over the following hospital days, his MTX level decreased very slowly and finally it reached to 0.10 µmol/L 10 days after high dose leucovorin rescue (Fig. 1). Following recovery, he proceeded to chemotherapy comprised of cisplatin (100 mg/m²) and doxorubicin (60 mg/m²). The second course of chemotherapy was comprised of a reduced MTX dose (6 g/m²), cisplatin (100 mg/m²) and doxorubicin (60 mg/m²), and it was completed uneventfully. After surgery, he had received all the scheduled chemotherapy, with the full dose of MTX (12 g/m²). He did not suffer any renal complication during postoperative chemotherapy and at present, he has been continuously disease free for 5 years.

A 7-year-old girl with osteosarcoma of the right distal femur received HD MTX (12 g/m²). She had previously undergone four courses of HD MTX uneventfully at another institution. The laboratory tests revealed asymptomatic microscopic hematuria, and yet her renal function (serum creatinine and creatinine clearance) was normal. She had not been administered any other nephrotoxic agent, such as cisplatin or ifosfamide. HD MTX was administered as described in case 1. During four hours of MTX administration, she suffered nausea and vomiting and the estimated amount of vomitus was about 150 mL. Her MTX level (4-hour) peaked at 1,630 µmol/L. Over the following 20 hours, she continuously suffered from nausea and vomiting. Her 24-hour MTX level was 892 µmol/L and leucovorin was immediately escalated to 1,000 mg/m² and administered every 3 hours. Her urine output slowly began to decrease and her serum creatinine level increased from 0.4 mg/dL to 1.8 mg/dL (Fig. 2). Diuretics were administered to maintain a urine output of above 50 mL/m²/hr. She complained of abdominal pain, nausea and experienced several episodes of vomiting. However, she did not experience any mucositis, diarrhea or leukopenia. Her serum MTX level decreased slowly, but it finally reached 0.13 µmol/L on the 16th day (384 hours after HD MTX administration). Upon recovery, she proceeded to surgery because her tumor size was increasing. Due to the poor response to preoperative chemotherapy, her postoperative chemotherapy was modified to the regimen comprised of cisplatin (100 mg/m²), doxorubicin (60 mg/m²), ifosfamide (14 g/m²) and bleomycin (30 mg/m²). At present, she has been continuously disease free for 6 years and is still suffering from intermittent hematuria.