Renal and Hepatic Clearance Following High-Dose Methotrexate in Childhood ALL

High-dose methotrexate therapy (HDMTX) is an important part of treatment of childhood acute lymphoblastic leukemia (ALL). HDMTX would be improved substantially if it were possible to predict the clearance of MTX for each patient and use this to tailor an individualized dosing of the drug. However, only about 3.7, 0.2, and 2% of the inter-individual variation in MTX clearance is explained by age, gender and ancestry, respectively. Genetic variation seems to explain about 10% of this difference, and SNPs in genes encoding transporter proteins (e.g. organic anion transporter 1B1 (OATP1B1) and reduced folate carrier (RFC)) are suggested to have a particular large impact. A serious limitation to the applicability of SNPs in prediction of MTX pharmacokinetics, however, is the substantial intra-individual variation in MTX clearance. The intra-individual variation in MTX clearance is related to renal function but a large amount of a HDMTX dose also enters the liver, where it is metabolized to 7-hydroxy MTX and probably also undergoes enterohepatic circulation. Thus, the aim of this study is to determine the role of the liver and renal function in MTX pharmacokinetics, and evaluate the predictive potential of pharmacogenetic (e.g. the rfc SNP) and pharmacokinetic parameters of MTX elimination during HDMTX.

Sex

All

Maximum age

19 Years

Inclusion Criteria:

* Admitted to Rigshospitalet
* Diagnosed with ALL
* Receiving high dose MTX

Exclusion Criteria:

* Using diaper (only exclusion criteria for the study part concerning urine collection)
* Above 19 years of age