• English
    • íslenska
  • English 
    • English
    • íslenska
  • Login
View Item 
  •   Home
  • Journal Articles, Peer Reviewed (Ritrýndar vísindagreinar)
  • English Journal Articles (Peer Reviewed)
  • View Item
  •   Home
  • Journal Articles, Peer Reviewed (Ritrýndar vísindagreinar)
  • English Journal Articles (Peer Reviewed)
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Browse

All of HirslaCommunitiesAuthorsTitleSubjectsSubject (MeSH)Issue DateJournalThis CollectionAuthorsTitleSubjectsSubject (MeSH)Issue DateJournal

My Account

LoginRegister

Local Links

FAQ - (Icelandic)FAQ - (English)Hirsla LogosAbout LandspitaliLSH Home PageLibrary HomeIcelandic Journals

Statistics

Display statistics

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity.

  • CSV
  • RefMan
  • EndNote
  • BibTex
  • RefWorks
Average rating
 
   votes
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item. When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
 
Your vote was cast
Thank you for your feedback
Authors
Levinsen, Mette
Rosthøj, Susanne
Nygaard, Ulrikka
Heldrup, Jesper
Harila-Saari, Arja
Jonsson, Olafur G
Bechensteen, Anne Grete
Abrahamsson, Jonas
Lausen, Birgitte
Frandsen, Thomas L
Weinshilboum, Richard M
Schmiegelow, Kjeld
Show allShow less
Issue Date
2015-01

Metadata
Show full item record
Citation
Cancer Chemother. Pharmacol. 2015, 75 (1):59-66
Abstract
Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMT(IA)) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT.
Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy.
The degree of myelosuppression following HD-MTX was similar for patients with TPMT(IA) and patients with high TPMT activity (TPMT(HA)), when HD-MTX started with same blood counts and 6MP doses. However, since TPMT(IA) had lower blood counts at initiation of HD-MTX compared with TPMT(HA) patients (median WBC 2.8 vs. 3.3 × 10⁹/L, P = 0.01; median ANC 1.4 vs. 1.7 × 10⁹/L, P = 0.02), TPMT(IA) continued to have lower WBC and ANC levels compared with TPMT(HA) during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2-17), P = 0.02 and 21 % (95 % CI 6-39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMT(IA) and TPMT(HA) patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses).
For both TPMT(IA) and TPMT(HA) patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity.
Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the page
Additional Links
http://dx.doi.org/ 10.1007/s00280-014-2613-7
http://download.springer.com/static/pdf/411/art%253A10.1007%252Fs00280-014-2613-7.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00280-014-2613-7&token2=exp=1439913327~acl=%2Fstatic%2Fpdf%2F411%2Fart%25253A10.1007%25252Fs00280-014-2613-7.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00280-014-2613-7*~hmac=4c35f6738c27866afa431cbe6758419b337965aa4e501b1336ab54da4ddb0fc1
Rights
Archived with thanks to Cancer chemotherapy and pharmacology
ae974a485f413a2113503eed53cd6c53
10.1007/s00280-014-2613-7
Scopus Count
Collections
English Journal Articles (Peer Reviewed)

entitlement

Related articles

  • Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia.
  • Authors: Nielsen SN, Grell K, Nersting J, Frandsen TL, Hjalgrim LL, Schmiegelow K
  • Issue date: 2016 Nov
  • Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia.
  • Authors: Vang SI, Schmiegelow K, Frandsen T, Rosthøj S, Nersting J
  • Issue date: 2015 May
  • 6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia.
  • Authors: Schmiegelow K, Bretton-Meyer U
  • Issue date: 2001 Jan
  • Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia.
  • Authors: Schmiegelow K, Björk O, Glomstein A, Gustafsson G, Keiding N, Kristinsson J, Mäkipernaa A, Rosthøj S, Szumlanski C, Sørensen TM, Weinshilboum R
  • Issue date: 2003 Apr 1
  • Mercaptopurine/Methotrexate maintenance therapy of childhood acute lymphoblastic leukemia: clinical facts and fiction.
  • Authors: Schmiegelow K, Nielsen SN, Frandsen TL, Nersting J
  • Issue date: 2014 Oct

DSpace software (copyright © 2002 - 2021)  DuraSpace
Quick Guide | Contact Us
Open Repository is a service operated by 
Atmire NV
 

Export search results

The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.