Evidence map›Paper›PMID 35354251›Full record

ArticleHaematologica2022

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes.

Stavroula Anastasopoulou, Rikke Linnemann Nielsen, Bodil Als-Nielsen, Joanna Banerjee, Mats A Eriksson, Marianne Helenius, Mats M Heyman, Inga Maria Johannsdottir, Olafur Gisli Jonsson, Stuart MacGregor and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
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  10. 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

22 authors.

Stavroula AnastasopoulouAstrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm. stavroula.anastasopoulou@ki.se.
Rikke Linnemann NielsenDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark; Present address: Novo Nordisk Research Centre Oxford, Oxford, OX3 7FZ.
Bodil Als-NielsenDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen.
Joanna BanerjeeDivision of Pediatric Hematology and Oncology and Stem Cell Transplantation, Helsinki University Hospital and Helsinki University, Helsinki.
Mats A ErikssonAstrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm.
Marianne HeleniusDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kgs. Lyngby.
Mats M HeymanAstrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm.
Inga Maria JohannsdottirDepartment of Pediatric Hematology/Oncology, Oslo University Hospital, Oslo, Norway.
Olafur Gisli JonssonDepartment of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland.
Stuart MacGregorQIMR Berghofer Medical Research Institute, Brisbane.
Marion K MateosKids Cancer Centre, Sydney Children's Hospital Randwick, Sydney, Australia; School of Clinical Medicine, Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW MEDICINE and HEALTH, UNSW Sydney; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney.
Chelsea MayohSchool of Clinical Medicine, Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW MEDICINE and HEALTH, UNSW Sydney; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney.
Sirje MikkelDepartment of Hematology and Oncology, University of Tartu, Tartu.
Ida Hed MyrbergChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
Riitta NiinimäkiDepartment of Children and Adolescents, Oulu University Hospital and University of Oulu, PEDEGO Research Unit, Oulu.
Kjeld SchmiegelowDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen.
Mervi TaskinenDivision of Pediatric Hematology and Oncology and Stem Cell Transplantation, Helsinki University Hospital and Helsinki University, Helsinki.
Goda VaitkevicieneChildren's Hospital, affiliate of Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius.
Anna WarnqvistDivision of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
Benjamin WolthersDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen.
Arja Harila-SaariDepartment of Women's and Children's Health, Uppsala University, Uppsala.
Susanna RantaAstrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.

Indexed as

Posterior Leukoencephalopathy SyndromePrecursor Cell Lymphoblastic Leukemia-LymphomaAntineoplastic Combined Chemotherapy ProtocolsAustraliaCentral Nervous SystemGenome-Wide Association StudyGenotypeHumansMethotrexatePhenotypeRisk FactorsSeizuresMethotrexate

Identifiers

PMID35354251
PMCPMC9521239

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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.