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

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Standard

Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia. / Larsen, Rikke Hebo; Utke Rank, Cecilie; Grell, Kathrine; Nørgaard Møller, Lisbeth; Malthe Overgaard, Ulrik; Kampmann, Peter; Nersting, Jacob; Degn, Matilda; Nygaard Nielsen, Stine; Holst, Helle; Klug Albertsen, Birgitte; Skov Wehner, Peder; Thude Callesen, Michael; Kanerva, Jukka; Leth Frandsen, Thomas; Als-Nielsen, Bodil; Lyngsie Hjalgrim, Lisa; Schmiegelow, Kjeld.

I: Haematologica, Bind 106, Nr. 11, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Larsen, RH, Utke Rank, C, Grell, K, Nørgaard Møller, L, Malthe Overgaard, U, Kampmann, P, Nersting, J, Degn, M, Nygaard Nielsen, S, Holst, H, Klug Albertsen, B, Skov Wehner, P, Thude Callesen, M, Kanerva, J, Leth Frandsen, T, Als-Nielsen, B, Lyngsie Hjalgrim, L & Schmiegelow, K 2021, 'Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia', Haematologica, bind 106, nr. 11. https://doi.org/10.3324/haematol.2020.278166

APA

Larsen, R. H., Utke Rank, C., Grell, K., Nørgaard Møller, L., Malthe Overgaard, U., Kampmann, P., Nersting, J., Degn, M., Nygaard Nielsen, S., Holst, H., Klug Albertsen, B., Skov Wehner, P., Thude Callesen, M., Kanerva, J., Leth Frandsen, T., Als-Nielsen, B., Lyngsie Hjalgrim, L., & Schmiegelow, K. (2021). Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia. Haematologica, 106(11). https://doi.org/10.3324/haematol.2020.278166

Vancouver

Larsen RH, Utke Rank C, Grell K, Nørgaard Møller L, Malthe Overgaard U, Kampmann P o.a. Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia. Haematologica. 2021;106(11). https://doi.org/10.3324/haematol.2020.278166

Author

Larsen, Rikke Hebo ; Utke Rank, Cecilie ; Grell, Kathrine ; Nørgaard Møller, Lisbeth ; Malthe Overgaard, Ulrik ; Kampmann, Peter ; Nersting, Jacob ; Degn, Matilda ; Nygaard Nielsen, Stine ; Holst, Helle ; Klug Albertsen, Birgitte ; Skov Wehner, Peder ; Thude Callesen, Michael ; Kanerva, Jukka ; Leth Frandsen, Thomas ; Als-Nielsen, Bodil ; Lyngsie Hjalgrim, Lisa ; Schmiegelow, Kjeld. / Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia. I: Haematologica. 2021 ; Bind 106, Nr. 11.

Bibtex

@article{99e211c62546439d87e5b2b8869aec44,
title = "Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia",
abstract = "Maintenance therapy containing Methotrexate (MTX) and 6-Mercaptopurine (6MP) is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG), and higher leucocyte DNA-TG is associated with increased relapse-free survival. As 6-Thioguanine (6TG) provides 6-fold higher cytosol TGN than 6MP, we added low-dose 6TG to MTX/6MP maintenance therapy to explore if this combination results in significantly higher DNA-TG. Target population of the {"}Thiopurine Enhanced ALL Maintenance therapy{"} (TEAM) study was n=30 patients, with non-high risk ALL, aged 1-45 years on MTX/6MP maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6TG were added to MTX/6MP maintenance therapy (start 6TG: 2.5 mg/m2/day, maximum: 12.5 mg/m2/day). Primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0-12.5 mg/m2/day as maximum 6TG dose. TEAM resulted in significantly higher DNA-TG, when compared with both TEAM patients before TEAM inclusion (on average 251 fmol/μg DNA higher (95% CI 160-341; P<0.0001), and with historical patients receiving standard MTX/6MP maintenance therapy (on average 272 fmol/μg DNA higher (95% CI 147-398; P<0.0001). TEAM did not increase myelotoxicity or hepatotoxicity. Conclusively, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG without inducing additional toxicity. It may therefore be an effective strategy to reduce risk of ALL relapse through increased DNA-TG, and this will be tested in a randomized ALLTogether-1 substudy.",
author = "Larsen, {Rikke Hebo} and {Utke Rank}, Cecilie and Kathrine Grell and {N{\o}rgaard M{\o}ller}, Lisbeth and {Malthe Overgaard}, Ulrik and Peter Kampmann and Jacob Nersting and Matilda Degn and {Nygaard Nielsen}, Stine and Helle Holst and {Klug Albertsen}, Birgitte and {Skov Wehner}, Peder and {Thude Callesen}, Michael and Jukka Kanerva and {Leth Frandsen}, Thomas and Bodil Als-Nielsen and {Lyngsie Hjalgrim}, Lisa and Kjeld Schmiegelow",
year = "2021",
doi = "10.3324/haematol.2020.278166",
language = "English",
volume = "106",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "11",

}

RIS

TY - JOUR

T1 - Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia

AU - Larsen, Rikke Hebo

AU - Utke Rank, Cecilie

AU - Grell, Kathrine

AU - Nørgaard Møller, Lisbeth

AU - Malthe Overgaard, Ulrik

AU - Kampmann, Peter

AU - Nersting, Jacob

AU - Degn, Matilda

AU - Nygaard Nielsen, Stine

AU - Holst, Helle

AU - Klug Albertsen, Birgitte

AU - Skov Wehner, Peder

AU - Thude Callesen, Michael

AU - Kanerva, Jukka

AU - Leth Frandsen, Thomas

AU - Als-Nielsen, Bodil

AU - Lyngsie Hjalgrim, Lisa

AU - Schmiegelow, Kjeld

PY - 2021

Y1 - 2021

N2 - Maintenance therapy containing Methotrexate (MTX) and 6-Mercaptopurine (6MP) is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG), and higher leucocyte DNA-TG is associated with increased relapse-free survival. As 6-Thioguanine (6TG) provides 6-fold higher cytosol TGN than 6MP, we added low-dose 6TG to MTX/6MP maintenance therapy to explore if this combination results in significantly higher DNA-TG. Target population of the "Thiopurine Enhanced ALL Maintenance therapy" (TEAM) study was n=30 patients, with non-high risk ALL, aged 1-45 years on MTX/6MP maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6TG were added to MTX/6MP maintenance therapy (start 6TG: 2.5 mg/m2/day, maximum: 12.5 mg/m2/day). Primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0-12.5 mg/m2/day as maximum 6TG dose. TEAM resulted in significantly higher DNA-TG, when compared with both TEAM patients before TEAM inclusion (on average 251 fmol/μg DNA higher (95% CI 160-341; P<0.0001), and with historical patients receiving standard MTX/6MP maintenance therapy (on average 272 fmol/μg DNA higher (95% CI 147-398; P<0.0001). TEAM did not increase myelotoxicity or hepatotoxicity. Conclusively, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG without inducing additional toxicity. It may therefore be an effective strategy to reduce risk of ALL relapse through increased DNA-TG, and this will be tested in a randomized ALLTogether-1 substudy.

AB - Maintenance therapy containing Methotrexate (MTX) and 6-Mercaptopurine (6MP) is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG), and higher leucocyte DNA-TG is associated with increased relapse-free survival. As 6-Thioguanine (6TG) provides 6-fold higher cytosol TGN than 6MP, we added low-dose 6TG to MTX/6MP maintenance therapy to explore if this combination results in significantly higher DNA-TG. Target population of the "Thiopurine Enhanced ALL Maintenance therapy" (TEAM) study was n=30 patients, with non-high risk ALL, aged 1-45 years on MTX/6MP maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6TG were added to MTX/6MP maintenance therapy (start 6TG: 2.5 mg/m2/day, maximum: 12.5 mg/m2/day). Primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0-12.5 mg/m2/day as maximum 6TG dose. TEAM resulted in significantly higher DNA-TG, when compared with both TEAM patients before TEAM inclusion (on average 251 fmol/μg DNA higher (95% CI 160-341; P<0.0001), and with historical patients receiving standard MTX/6MP maintenance therapy (on average 272 fmol/μg DNA higher (95% CI 147-398; P<0.0001). TEAM did not increase myelotoxicity or hepatotoxicity. Conclusively, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG without inducing additional toxicity. It may therefore be an effective strategy to reduce risk of ALL relapse through increased DNA-TG, and this will be tested in a randomized ALLTogether-1 substudy.

U2 - 10.3324/haematol.2020.278166

DO - 10.3324/haematol.2020.278166

M3 - Journal article

C2 - 34047177

VL - 106

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 11

ER -

ID: 272017894