Title:

Factors affecting elimination and clinical tolerance of high doses of methotrexate, administered as remission consolidation therapy in children with acute lymphoblastic leukemia

Author:

Ćwiklińska, Magdalena

Subject:

acute lymphoblastic leukemia ; high doses of methotrexate ; monitored therapy ; early toxicities ; children

Abstract:

This study included 852 chemotherapy cycles with methotexate (Mtx), administered in the dose of 2 g/m2 and 3 g/m2 to 218 children with acute lymphoblastic leukemia. Prolonged Mtx elimination was observed in about 17% of cycles and 45% of patients. Major factors that affected Mtx elimination included: higer steady-state Mtx levels and impairment of drug clearance in the early phase of its rapid elimination. Considerable variability of Mtx pharmacokinetics, demonstrated in the study, is an argument for adapting the dose to a current, variable clearance of the drug in a given patient. In general tolerance of high doses of Mtx was good and was not associated with intensified (grade 3 and 4) or prolonged toxicities. The most common early complications were: hepatic dysfunction, nausea and vomiting and oral mucositis. The most significant factor affecting the intensity of early toxicity was prolonged exposure to cytotoxic concentrations of Mtx. The high risk group for intensified early toxicities of high doses Mtx therapy includes: patients with higher serum steady-state drug levels, characterized by slower drug elimination and lower coefficient of elimination in the early phase of drug excretion, children above 10 years of life and patients during the first chemotherapy cycle with Mtx.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

hematologia ; farmakologia

Degree grantor:

Uniwersytet Jagielloński – Collegium Medicum

Promoter:

Balwierz, Walentyna

Date:

2009

Date issued:

2009

Type:

Praca doktorska

Call number:

ZB-110922

Language:

pol

Access rights:

nieograniczony