Evidence map›Paper›PMID 34625787›Full record

ArticleBlood advances2022

Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia: a NOPHO ALL2008 study.

Line Stensig Lynggaard, Cecilie Utke Rank, Stefan Nygaard Hansen, Sofie Gottschalk Højfeldt, Louise Tram Henriksen, Kirsten Brunsvig Jarvis, Susanna Ranta, Riitta Niinimäki, Arja Harila-Saari, Benjamin O Wolthers and 4 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  4. Activity and toxicity of intramuscular 1000 iu/mBritish journal of haematology · 2022
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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

14 authors at 7 institutions in 4 countries.

Line Stensig LynggaardDepartment of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0002-8584-5920
Cecilie Utke RankDepartment of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-0578-3887
Stefan Nygaard HansenDepartment of Public Health, Aarhus University, Aarhus, Denmark.
Sofie Gottschalk HøjfeldtDepartment of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0003-2695-8391
Louise Tram HenriksenDepartment of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0002-9350-1538
Kirsten Brunsvig JarvisDepartment of Paediatric Haematology and Oncology, Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-8996-1195
Susanna RantaAstrid Lindgren Children's Hospital, Karolinska University Hospital and Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7854-0371
Riitta NiinimäkiDepartment of Paediatrics and Adolescent Medicine, Oulu University Hospital and PEDEGO unit, University of Oulu, Oulu, Finland.ORCID 0000-0003-0190-5664
Arja Harila-SaariDepartment of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Benjamin O WolthersDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Thomas L FrandsenDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-8495-5274
Mats HeymanAstrid Lindgren Children's Hospital, Karolinska University Hospital and Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7637-1949
Kjeld SchmiegelowDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-0829-4993
Birgitte Klug AlbertsenDepartment of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0002-3902-3694
University of Copenhagen · DKAarhus University · DKAarhus University Hospital · DKKarolinska University Hospital · SEOslo University Hospital · NOOulu University Hospital · FIUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with ≥2 blood samples for AEA measurement drawn 14 ± 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.

Indexed as

Antineoplastic AgentsPrecursor Cell Lymphoblastic Leukemia-LymphomaThromboembolismAdolescentAsparaginaseChildChild, PreschoolHumansInfantPolyethylene GlycolsAntineoplastic AgentsAsparaginasePolyethylene Glycols

Identifiers

PMID34625787
PMCPMC8753199
OpenAlexW3204801713

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.