Conflict of interest: Nothing to declare.
High dose methotrexate treatment in children with acute lymphoblastic leukaemia may be optimised by a weight-based dose calculation†
Article first published online: 21 MAR 2011
Copyright © 2011 Wiley-Liss, Inc.
Pediatric Blood & Cancer
Volume 57, Issue 1, pages 41–46, 15 July 2011
How to Cite
Jönsson, P., Skärby, T., Heldrup, J., Schrøder, H. and Höglund, P. (2011), High dose methotrexate treatment in children with acute lymphoblastic leukaemia may be optimised by a weight-based dose calculation. Pediatr. Blood Cancer, 57: 41–46. doi: 10.1002/pbc.22999
- Issue published online: 9 MAY 2011
- Article first published online: 21 MAR 2011
- Manuscript Accepted: 6 DEC 2010
- Manuscript Received: 21 JAN 2010
- Children's Cancer Foundation of Sweden
- Swedish Cancer Society
- B. Kamprad's
- Gyllenstiern's Krapperup
- Lund University Hospital Foundations
- acute lymphoblastic leukaemia;
- dose normalisation;
- relapse risk
The inter-individual variation in exposure to methotrexate is considerable after intravenous high dose methotrexate (HDMTX) administration and both under- and over exposures may have dire consequences. Thus, optimal dose individualisation is of paramount importance.
We studied how pharmacokinetic parameters were related to outcome in 340 patients with acute lymphoblastic leukaemia (ALL). A population pharmacokinetic model was developed with data from 1284 HDMTX courses in 304 children evaluating age, height, weight, body surface area (BSA), sex, serum creatinine and serum alanine aminotransferase as potential covariates.
Body weight improved the population pharmacokinetic model significantly more than any of the other patient characteristics, indicating that body weight may be the better way of dose normalisation. In a logistic regression analysis, higher values of clearance as well as volume of distribution were related to increased relapse risk in the standard (SR) and intermediate risk (IR) groups as well as in the entire cohort. A higher weight was strongly associated with worse outcome in the SR and IR groups, (P = 0.0186 and 0.0121, respectively).
We conclude that dose normalisation of methotrexate according to body weigh may give more predictable pharmacokinetics of methotrexate and may also improve the outcome for children with ALL. Pediatr Blood Cancer 2011;57:41–46. © 2011 Wiley-Liss, Inc.