Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia

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Larsen , R H , Rank , C U , Grell , K , Moller , L N , Overgaard , U M , Kampmann , P , Nersting , J , Degn , M , Nielsen , S N , Holst , H , Albertsen , B K , Wehner , P S , Callesen , M T , Kanerva , J , Frandsen , T L , Als-Nielsen , B , Hjalgrim , L L & Schmiegelow , K 2021 , ' Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia ' , Haematologica , vol. 106 , no. 11 , pp. 2824-2833 . https://doi.org/10.3324/haematol.2020.278166

Title: Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia
Author: Larsen, Rikke Hebo; Rank, Cecilie Utke; Grell, Kathrine; Moller, Lisbeth Norgaard; Overgaard, Ulrik Malthe; Kampmann, Peter; Nersting, Jacob; Degn, Matilda; Nielsen, Stine Nygaard; Holst, Helle; Albertsen, Birgitte Klug; Wehner, Peder Skov; Callesen, Michael Thude; Kanerva, Jukka; Frandsen, Thomas Leth; Als-Nielsen, Bodil; Hjalgrim, Lisa Lyngsie; Schmiegelow, Kjeld
Contributor organization: HUS Children and Adolescents
Children's Hospital
Date: 2021-11
Language: eng
Number of pages: 10
Belongs to series: Haematologica
ISSN: 0390-6078
DOI: https://doi.org/10.3324/haematol.2020.278166
URI: http://hdl.handle.net/10138/337331
Abstract: Maintenance therapy containing methotrexate and 6-mercaptopurine is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides into DNA (DNA-TG), and higher leukocyte DNA-TG is associated with increased relapse-free survival. As 6-thioguanine provides 6-fold higher cytosolic levels of thioguanine nucleotides than does 6-mercaptopurine, we added low-dose 6-thioguanine to methotrexate/6-mercaptopurine maintenance therapy to explore if this combination results in significantly higher DNA-TG. The target population of the "Thiopurine Enhanced ALL Maintenance therapy" (TEAM) study was 30 patients with non-high-risk ALL, aged 1-45 years on methotrexate/6-mercaptopurine maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6-thioguanine were added to methotrexate/6-mercaptopurine maintenance therapy (starting 6-thioguanine dose: 2.5 mg/m(2)/day, maximum: 12.5 mg/m(2)/day). The primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to the TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0-12.5 mg/m(2)/day as the maximum 6-thioguanine dose. TEAM resulted in significantly higher DNA-TG levels compared to those in both TEAM patients before their inclusion in TEAM (on average 251 fmol/mu g DNA higher [95% confidence interval: 160-341; P
Subject: FASTING HYPOGLYCEMIA
NOPHO ALL2008
CHILDHOOD
CHILDREN
6-THIOGUANINE
RELAPSE
RISK
6-MERCAPTOPURINE
INTENSIFICATION
MERCAPTOPURINE
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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