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TPMT polymorphisms ...
TPMT polymorphisms and minimal residual disease after 6-mercaptopurine post-remission consolidation therapy of childhood acute lymphoblastic leukaemia
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Dreisig, Karin (author)
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Brünner, Emilie Damgaard (author)
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Marquart, Hanne V. (author)
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Helt, Louise Rold (author)
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Nersting, Jacob (author)
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Frandsen, Thomas Leth (author)
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Jonsson, Olafur Gisli (author)
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Taskinen, Mervi (author)
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Vaitkeviciene, Goda (author)
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Lund, Bendik (author)
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- Abrahamsson, Jonas, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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Lepik, Kristi (author)
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Schmiegelow, Kjeld (author)
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(creator_code:org_t)
- 2020-11-18
- 2021
- English.
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In: Pediatric Hematology and Oncology. - : Informa UK Limited. - 0888-0018 .- 1521-0669. ; 38:3, s. 227-238
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Abstract
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- © 2020 Taylor & Francis Group, LLC. Bone marrow minimal residual disease (MRD) is the strongest predictor of relapse in children with acute lymphoblastic leukemia (ALL). 6-mercaptopurine (6MP) in ALL therapy has wide inter-individual variation in disposition and is strongly influenced by polymorphisms in the thiopurine methyltransferase (TPMT) gene. In 952 patients treated according to the NOPHO ALL2008 protocol, we explored the association between thiopurine disposition, TPMT genotypes and MRD levels after consolidation therapy with 6MP, high-dose methotrexate (HD-MTX), asparaginase, and vincristine. The levels of the cytotoxic DNA-incorporated thioguanine were significantly higher on day 70-79 in G460A/A719G TPMT heterozygous (TPMT HZ) compared to TPMT wild type (TPMT WT) patients (mean: 230.7 vs. 149.7 fmol/µg DNA, p = 0.002). In contrast, TPMT genotype did not associate with the end of consolidation MRD levels irrespective of randomization of the patients to fixed dose (25 mg/m2/day) or 6MP escalation (up to 50 or 75 mg/m2/day) during consolidation therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- 6-mercaptopurine
- Childhood acute lymphoblastic leukemia
- minimal residual disease
- thiopurine methyltransferase
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dreisig, Karin
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Brünner, Emilie ...
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Marquart, Hanne ...
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Helt, Louise Rol ...
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Nersting, Jacob
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Frandsen, Thomas ...
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show more...
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Jonsson, Olafur ...
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Taskinen, Mervi
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Vaitkeviciene, G ...
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Lund, Bendik
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Abrahamsson, Jon ...
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Lepik, Kristi
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Schmiegelow, Kje ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Pediatrics
- Articles in the publication
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Pediatric Hemato ...
- By the university
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University of Gothenburg