@article{Larsen_Utke Rank_Grell_Nørgaard Møller_Malthe Overgaard_Kampmann_Nersting_Degn_Nygaard Nielsen_Holst_Klug Albertsen_Skov Wehner_Thude Callesen_Kanerva_Leth Frandsen_Als-Nielsen_Lyngsie Hjalgrim_Schmiegelow_2021, place={Pavia, Italy}, title={Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia}, volume={106}, url={https://haematologica.org/article/view/haematol.2020.278166}, DOI={10.3324/haematol.2020.278166}, abstractNote={<p>Maintenance therapy containing methotrexate and 6-mercapto - purine 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- mercapto purine, we added low-dose 6-thioguanine to methotrexate/6- mercapto purine 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<sup>2</sup>/day, maximum: 12.5 mg/m<sup>2</sup>/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<sup>2</sup>/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/mg DNA higher [95% confidence interval: 160-341; <em>P</em>&lt;0.0001]), and with historical patients receiving standard methotrexate/6-mercapto - purine maintenance therapy (on average 272 fmol/mg DNA higher [95% confidence interval: 147-398; <em>P</em>&lt;0.0001]). TEAM did not increase myelotoxicity or hepatotoxicity. In conclusion, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG levels without inducing additional toxicity. It may therefore be an effective strategy to reduce the risk of ALL relapse through increased DNA-TG. This will be tested in a randomized ALLTogether-1 substudy.</p&gt;}, number={11}, journal={Haematologica}, author={Larsen, Rikke Hebo and Utke Rank, Cecilie and Grell, Kathrine and Nørgaard Møller, Lisbeth and Malthe Overgaard, Ulrik and Kampmann, Peter and Nersting, Jacob and Degn, Matilda and Nygaard Nielsen, Stine and Holst, Helle and Klug Albertsen, Birgitte and Skov Wehner, Peder and Thude Callesen, Michael and Kanerva, Jukka and Leth Frandsen, Thomas and Als-Nielsen, Bodil and Lyngsie Hjalgrim, Lisa and Schmiegelow, Kjeld}, year={2021}, month={Nov.}, pages={2824-2833} }