Evaluation of Serious Adverse Events in Patients Treated with Protocols Including Methotrexate Infusions

Abstract

During the period 1979 to 1992 we treated 141 children for various malignant diseases with protocols including methotrexate (MTX) infusions in doses ranging from 0.5 to 33.6 g/m2. During a total of 922 courses, there were no fatal complications associated with MTX treatment. Serum MTX concentration and pharmacokinetic data were monitored continuously during the infusions. In this study, we evaluated the occurrence of serious untoward reactions to MTX infusions. Impaired renal function with delayed drug elimination was seen in seven patients, all boys, especially after short infusion times. All recovered completely without any serious clinical symptoms. In three leukemia patients who later died from resistant disease, we observed late neurological disturbances and computer tomography (CT) brain scan abnormalities. Pharmacokinetic data from the patients with complications are described and confirm that serial MTX concentration monitoring is the most important early indicator of renal toxicity.

Renal function during and after treatment for acute lymphoblastic leukemia in children

“…This can precipitate in renal tubules and cause acute renal impairment. Moreover, the concomitant use of other cytostatics with less nephrotoxic effect and other nephrotoxins such as aminoglycoside antibiotics, vancomycin, and amphotericin B may provoke renal failure [1,2,9,10,11,12]. Cyclophosphamide, used in the Berlin-Frankfurt-Münster 95 protocol, induces hemorrhagic cystitis manifested such as a microscopic hematuria or bloody urine.…”

Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long‐term follow‐up: Value of renal scan

“…Effects of therapeutic approaches and different complications are mostly directly related to the kidney [1][2][3][4][5][6][7][8][9].…”

“…Infiltration of kidneys by leukemic cells, nephrotoxicity, and metabolic changes arising from chemotherapy, radiotherapy, infections, treatment with nephrotoxic antibiotics, and intravascular coagulopathy may cause renal damage [1][2][3][4][5][6][7][8][9]. During the last 30 years, the prognosis of acute lymphoblastic leukemia (ALL) has improved due to intensive chemotherapy and better supportive therapy.…”

Influence of high‐dose methotrexate therapy (HD‐MTX) on glomerular and tubular kidney function

“…This corresponds to the positive clinical experience that severe renal dysfunction due to MTX administration is rare [5,23,24]. However, it is also not possible as yet to explain the reasons for changes if serious renal damage due to MTX occur.…”