Evidence map›Paper›PMID 33928426›Full record

ArticleCancer chemotherapy and pharmacology2021

No association between relapse hazard and thiopurine methyltransferase geno- or phenotypes in non-high risk acute lymphoblastic leukemia: a NOPHO ALL2008 sub-study.

Stine Nygaard Nielsen, Linea Natalie Toksvang, Kathrine Grell, Jacob Nersting, Jonas Abrahamsson, Bendik Lund, Jukka Kanerva, Ólafur Gísli Jónsson, Goda Vaitkeviciene, Kaie Pruunsild and 3 more

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In one paragraph

Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 2 syntheses or guidelines pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Association ofHaematologica · 2024
    Pooled it
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 7 countries.

Stine Nygaard NielsenDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Linea Natalie ToksvangDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-9871-7637
Kathrine GrellDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-6398-6979
Jacob NerstingDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-9144-7972
Jonas AbrahamssonSahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-9240-3522
Bendik LundDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Jukka KanervaChildren's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Ólafur Gísli JónssonPediatric Hematology-Oncology, Barnaspitali Hringsins, Landspitali University Hospital, Reykjavik, Iceland.
Goda VaitkevicieneCentre for Paediatric Oncology and Haematology, Vilnius University, Vilnius, Lithuania.
Kaie PruunsildDepartment of Oncology and Haematology, Tallinn Children's Hospital, Tallinn, Estonia.
Malin Lindqvist AppellFaculty of Medicine and Health Sciences, Division of Drug Research, Linköping University, Linköping, Sweden.ORCID 0000-0002-2809-7591
Lisa Lyngsie HjalgrimDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-5186-3365
Kjeld SchmiegelowDepartment of Pediatrics and Adolescent Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. kjeld.schmiegelow@regionh.dk.ORCID 0000-0002-0829-4993
University of Copenhagen · DKLinköping University · SENational University Hospital of Iceland · ISNorwegian University of Science and Technology · NOTallinn Health Care College · EEUniversity of Gothenburg · SEUniversity of Helsinki · FIVilnius University · LT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purpose6-mercaptopurine(6MP)/methotrexate maintenance therapy is essential to reduce relapse of childhood acute lymphoblastic leukemia (ALL). Common germline variants in TPMT cause low activity of thiopurine methyltransferase (TPMT) and higher 6MP metabolite (TGN) levels. Higher levels of TGNs incorporated into DNA (DNA-TG) and low TPMT activity have previously been associated with a lower relapse risk. We explored if TPMT geno- or phenotype was associated with DNA-TG levels and relapse rate in NOPHO ALL2008.

methodsTPMT genotype, repeated phenotyping, and DNA-TG measurements were collected in 918 children with non-high risk ALL (NOPHO ALL2008 maintenance therapy study). Maintenance therapy started with 6MP at 50 and 75 mg/m

resultsOf 918 patients, 78 (8.5%) were TPMT heterozygous and 903 had at least one TPMT measurement (total 3063). Mean TPMT activities were higher with wildtype than heterozygous TPMT (N = 752, 16.6 versus 9.6 U/mL ery., p < 0.001). The 5-year cumulative incidence of relapse was 6.4% and 6.0% for TPMT heterozygous and wildtype patients, and there was no association between genotype and relapse rate (N = 918, hazard ratio = 1.01, 95% confidence interval [CI] 0.40 - 2.54, p = 0.98). Although TPMT heterozygous patients had higher DNA-TG (N = 548, median 760.9 [interquartile range (IQR) 568.7 - 890.3] versus 492.7 [IQR 382.1 - 634.6] fmol/µg, p < 0.001), TPMT activity was not associated with relapse rate (N = 813; hazard ratio = 0.98 per one U/mL ery. increase in TPMT activity, 95% CI 0.91 - 1.06, p = 0.67).

conclusionTPMT geno- and phenotype were not associated with relapse in non-high risk NOPHO ALL2008.

Indexed as

AdolescentAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsChildChild, PreschoolDNAFemaleGenotypeHumansInfantMaleMercaptopurineMethotrexateMethyltransferasesPhenotypePrecursor Cell Lymphoblastic Leukemia-LymphomaAntimetabolites, AntineoplasticDNAMercaptopurineMethotrexateMethyltransferasesthiopurine methyltransferase6-mercaptopurineChildhood acute lymphoblastic leukemiaMaintenance therapyRelapseThiopurine methyltransferase

Identifiers

PMID33928426
OpenAlexW3158173546

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.