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Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia

Jönsson, Peter LU ; Höglund, Peter LU ; Wiebe, Thomas LU ; Schroder, Henrik; Seidel, Holger and Skärby, Tor LU (2007) In Anti-Cancer Drugs 18(8). p.941-948
Abstract
The aim of the study was to characterize the relationship between the pharmacolkinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 children with acute lymphoblastic leukaemia treated with high-dose methotrexate according to the Nordic Society of Pediatric Haematology and Oncology-92 acute lymphoblastic leukaemia protocol were studied. Data from 18 patients with a subsequent central nervous system relapse and 335 event-free patients were available. In 34 patients the methotrexate concentrations were monitored repeatedly during each 24-h methotrexate... (More)
The aim of the study was to characterize the relationship between the pharmacolkinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 children with acute lymphoblastic leukaemia treated with high-dose methotrexate according to the Nordic Society of Pediatric Haematology and Oncology-92 acute lymphoblastic leukaemia protocol were studied. Data from 18 patients with a subsequent central nervous system relapse and 335 event-free patients were available. In 34 patients the methotrexate concentrations were monitored repeatedly during each 24-h methotrexate intravenous infusion and a cerebrospinal fluid sample was taken at the end of the infusion. Using statistics separating interindividual and intraindividual variability, methotrexate concentration in cerebrospinal fluid was found to be significantly dependent upon both serum concentrations at the end of infusion and the area under the concentration curve in serum (P<0.0017 and <0.002, respectively). The logistic regression analysis revealed that high patient median serum methotrexate concentrations at the end of infusion were significantly associated with decreased risk for a central nervous system relapse in the standard risk group (P=0.02) and the number of courses with a calculated cerebrospinal fluid concentration of more than 1 mu mol/l (P=0.048) with a decreased risk of a central nervous system relapse in the combined (standard risk and intermediate) risk group. In conclusion, methotrexate concentrations in cerebrospinal fluid are dependent on methotrexate concentrations in serum and serum area under the concentration curve. Multivariate analysis indicates that an increased exposure to methotrexate is related to decreased risk for central nervous system relapse. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
concentration in cerebrospinal fluid, acute lymphoblastic leukaemia, central nervous system relapse, methotrexate
in
Anti-Cancer Drugs
volume
18
issue
8
pages
941 - 948
publisher
Rapid Communications
external identifiers
  • wos:000248795300010
  • scopus:34547661701
ISSN
0959-4973
language
English
LU publication?
yes
id
6ea90487-25a0-40dd-a122-8693855b2f35 (old id 692930)
alternative location
http://www.anti-cancerdrugs.com/pt/re/anticd/abstract.00001813-200709000-00010.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17667600&dopt=Abstract
date added to LUP
2007-12-13 14:28:21
date last changed
2017-06-25 03:35:46
@article{6ea90487-25a0-40dd-a122-8693855b2f35,
  abstract     = {The aim of the study was to characterize the relationship between the pharmacolkinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 children with acute lymphoblastic leukaemia treated with high-dose methotrexate according to the Nordic Society of Pediatric Haematology and Oncology-92 acute lymphoblastic leukaemia protocol were studied. Data from 18 patients with a subsequent central nervous system relapse and 335 event-free patients were available. In 34 patients the methotrexate concentrations were monitored repeatedly during each 24-h methotrexate intravenous infusion and a cerebrospinal fluid sample was taken at the end of the infusion. Using statistics separating interindividual and intraindividual variability, methotrexate concentration in cerebrospinal fluid was found to be significantly dependent upon both serum concentrations at the end of infusion and the area under the concentration curve in serum (P&lt;0.0017 and &lt;0.002, respectively). The logistic regression analysis revealed that high patient median serum methotrexate concentrations at the end of infusion were significantly associated with decreased risk for a central nervous system relapse in the standard risk group (P=0.02) and the number of courses with a calculated cerebrospinal fluid concentration of more than 1 mu mol/l (P=0.048) with a decreased risk of a central nervous system relapse in the combined (standard risk and intermediate) risk group. In conclusion, methotrexate concentrations in cerebrospinal fluid are dependent on methotrexate concentrations in serum and serum area under the concentration curve. Multivariate analysis indicates that an increased exposure to methotrexate is related to decreased risk for central nervous system relapse.},
  author       = {Jönsson, Peter and Höglund, Peter and Wiebe, Thomas and Schroder, Henrik and Seidel, Holger and Skärby, Tor},
  issn         = {0959-4973},
  keyword      = {concentration in cerebrospinal fluid,acute lymphoblastic leukaemia,central nervous system relapse,methotrexate},
  language     = {eng},
  number       = {8},
  pages        = {941--948},
  publisher    = {Rapid Communications},
  series       = {Anti-Cancer Drugs},
  title        = {Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia},
  volume       = {18},
  year         = {2007},
}