DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.
To access publisher's full text version of this article click on the hyperlink below Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated...
Published in: | The Lancet Oncology |
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Main Authors: | , , , , , , , , , , |
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Format: | Article in Journal/Newspaper |
Language: | English |
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Elsevier Science Publishers
2017
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Online Access: | http://hdl.handle.net/2336/620155 https://doi.org/10.1016/S1470-2045(17)30154-7 |
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Hirsla - Landspítali University Hospital research archive |
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Bráðahvítblæði Hvítblæði Börn PED12 Precursor Cell Lymphoblastic Leukemia-Lymphoma |
spellingShingle |
Bráðahvítblæði Hvítblæði Börn PED12 Precursor Cell Lymphoblastic Leukemia-Lymphoma Nielsen, Stine Nygaard Grell, Kathrine Nersting, Jacob Abrahamsson, Jonas Lund, Bendik Kanerva, Jukka Jónsson, Ólafur Gísli Vaitkeviciene, Goda Pruunsild, Kaie Hjalgrim, Lisa Lyngsie Schmiegelow, Kjeld DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
topic_facet |
Bráðahvítblæði Hvítblæði Börn PED12 Precursor Cell Lymphoblastic Leukemia-Lymphoma |
description |
To access publisher's full text version of this article click on the hyperlink below Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m(2) once per day and methotrexate 20 mg/m(2) once per week, targeted to a leucocyte count of 1·5-3·0 × 10(9) cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2. Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR ... |
author2 |
1 Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Show the Organization-Enhanced name(s) 2 Univ Copenhagen, Dept Publ Hlth, Sect Biostat, Copenhagen, Denmark Show the Organization-Enhanced name(s) 3 Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark Show the Organization-Enhanced name(s) 4 Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden Show the Organization-Enhanced name(s) 5 St Olavs Hosp, Dept Pediat, Trondheim, Norway Show the Organization-Enhanced name(s) 6 Norwegian Univ Sci & Technol, Fac Med, Dept Lab Med Childrens & Womens Hlth, Trondheim, Norway Show the Organization-Enhanced name(s) 7 Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland Show the Organization-Enhanced name(s) 8 Univ Helsinki, Helsinki, Finland Show the Organization-Enhanced name(s) 9 Landspitali Univ Hosp, Barnaspitali Hringsins, Pediat Hematol Oncol, Reykjavik, Iceland 10 Univ Childrens Hosp, Ctr Paediat Oncol & Haematol, Vilnius, Lithuania 11 Tallinn Childrens Hosp, Dept Haematol & Oncol, Tallinn, Estonia |
format |
Article in Journal/Newspaper |
author |
Nielsen, Stine Nygaard Grell, Kathrine Nersting, Jacob Abrahamsson, Jonas Lund, Bendik Kanerva, Jukka Jónsson, Ólafur Gísli Vaitkeviciene, Goda Pruunsild, Kaie Hjalgrim, Lisa Lyngsie Schmiegelow, Kjeld |
author_facet |
Nielsen, Stine Nygaard Grell, Kathrine Nersting, Jacob Abrahamsson, Jonas Lund, Bendik Kanerva, Jukka Jónsson, Ólafur Gísli Vaitkeviciene, Goda Pruunsild, Kaie Hjalgrim, Lisa Lyngsie Schmiegelow, Kjeld |
author_sort |
Nielsen, Stine Nygaard |
title |
DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
title_short |
DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
title_full |
DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
title_fullStr |
DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
title_full_unstemmed |
DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. |
title_sort |
dna-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (nopho all2008): a prospective substudy of a phase 3 trial. |
publisher |
Elsevier Science Publishers |
publishDate |
2017 |
url |
http://hdl.handle.net/2336/620155 https://doi.org/10.1016/S1470-2045(17)30154-7 |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://ac.els-cdn.com/S1470204517301547/1-s2.0-S1470204517301547-main.pdf?_tid=b99f8fc6-2443-11e7-b430-00000aab0f6c&acdnat=1492526075_bb163090685d46917c822d56d1e8a8e5 DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. 2017, 18 (4):515-524 Lancet Oncol. 1474-5488 28258828 doi:10.1016/S1470-2045(17)30154-7 http://hdl.handle.net/2336/620155 The Lancet. Oncology |
op_rights |
Archived with thanks to The Lancet. Oncology National Consortium - Landsaðgangur |
op_doi |
https://doi.org/10.1016/S1470-2045(17)30154-7 |
container_title |
The Lancet Oncology |
container_volume |
18 |
container_issue |
4 |
container_start_page |
515 |
op_container_end_page |
524 |
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1766043195318206464 |
spelling |
ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/620155 2023-05-15T16:52:47+02:00 DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. Nielsen, Stine Nygaard Grell, Kathrine Nersting, Jacob Abrahamsson, Jonas Lund, Bendik Kanerva, Jukka Jónsson, Ólafur Gísli Vaitkeviciene, Goda Pruunsild, Kaie Hjalgrim, Lisa Lyngsie Schmiegelow, Kjeld 1 Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Show the Organization-Enhanced name(s) 2 Univ Copenhagen, Dept Publ Hlth, Sect Biostat, Copenhagen, Denmark Show the Organization-Enhanced name(s) 3 Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark Show the Organization-Enhanced name(s) 4 Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden Show the Organization-Enhanced name(s) 5 St Olavs Hosp, Dept Pediat, Trondheim, Norway Show the Organization-Enhanced name(s) 6 Norwegian Univ Sci & Technol, Fac Med, Dept Lab Med Childrens & Womens Hlth, Trondheim, Norway Show the Organization-Enhanced name(s) 7 Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland Show the Organization-Enhanced name(s) 8 Univ Helsinki, Helsinki, Finland Show the Organization-Enhanced name(s) 9 Landspitali Univ Hosp, Barnaspitali Hringsins, Pediat Hematol Oncol, Reykjavik, Iceland 10 Univ Childrens Hosp, Ctr Paediat Oncol & Haematol, Vilnius, Lithuania 11 Tallinn Childrens Hosp, Dept Haematol & Oncol, Tallinn, Estonia 2017 http://hdl.handle.net/2336/620155 https://doi.org/10.1016/S1470-2045(17)30154-7 en eng Elsevier Science Publishers http://ac.els-cdn.com/S1470204517301547/1-s2.0-S1470204517301547-main.pdf?_tid=b99f8fc6-2443-11e7-b430-00000aab0f6c&acdnat=1492526075_bb163090685d46917c822d56d1e8a8e5 DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. 2017, 18 (4):515-524 Lancet Oncol. 1474-5488 28258828 doi:10.1016/S1470-2045(17)30154-7 http://hdl.handle.net/2336/620155 The Lancet. Oncology Archived with thanks to The Lancet. Oncology National Consortium - Landsaðgangur Bráðahvítblæði Hvítblæði Börn PED12 Precursor Cell Lymphoblastic Leukemia-Lymphoma Article 2017 ftlandspitaliuni https://doi.org/10.1016/S1470-2045(17)30154-7 2022-05-29T08:22:13Z To access publisher's full text version of this article click on the hyperlink below Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m(2) once per day and methotrexate 20 mg/m(2) once per week, targeted to a leucocyte count of 1·5-3·0 × 10(9) cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2. Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR ... Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive Norway The Lancet Oncology 18 4 515 524 |