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Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia
- Source :
- 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, vol. 106, no. 11, pp. 2824-2833 . https://doi.org/10.3324/haematol.2020.278166, Larsen, R H, Rank, C U, Grell, K, Møller, 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, Haematologica, 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, vol. 106, no. 11 . https://doi.org/10.3324/haematol.2020.278166
- Publication Year :
- 2021
-
Abstract
- aintenance 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-mercaptopurine, we added low-dose 6-thioguanine to methotrexate/6mercaptopurine 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/m2/day, maximum: 12.5 mg/m2/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/m2/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; P
- Subjects :
- Purine
Adult
medicine.medical_specialty
Adolescent
FASTING HYPOGLYCEMIA
6-THIOGUANINE
3122 Cancers
CHILDHOOD
CHILDREN
RELAPSE
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Maintenance therapy
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
medicine
Humans
Child
Thioguanine
RISK
6-MERCAPTOPURINE
Thiopurine methyltransferase
biology
business.industry
Mercaptopurine
INTENSIFICATION
Editorials
Infant
Hematology
DNA
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Confidence interval
3. Good health
chemistry
Child, Preschool
Toxicity
biology.protein
Methotrexate
business
NOPHO ALL2008
030215 immunology
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 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, vol. 106, no. 11, pp. 2824-2833 . https://doi.org/10.3324/haematol.2020.278166, Larsen, R H, Rank, C U, Grell, K, Møller, 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, Haematologica, 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, vol. 106, no. 11 . https://doi.org/10.3324/haematol.2020.278166
- Accession number :
- edsair.doi.dedup.....02df15f6cb2dc222fe91b103108e1623