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

Anastasopoulou, Stavroula (författare)
Karolinska Institutet
Nielsen, Rikke Linnemann (författare)
Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark.;Novo Nordisk Res Ctr Oxford, Oxford, Oxfordshire, England.
Als-Nielsen, Bodil (författare)
Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.
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Banerjee, Joanna (författare)
Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland.
Eriksson, Mats A. (författare)
Karolinska Institutet
Helenius, Marianne (författare)
Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark.
Heyman, Mats M. (författare)
Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Neuropediat Unit, Stockholm, Sweden.
Johannsdottir, Inga Maria (författare)
Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway.
Jonsson, Olafur Gisli (författare)
Landspitali Univ Hosp, Dept Pediat, Reykjavik, Iceland.
MacGregor, Stuart (författare)
QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
Mateos, Marion K. (författare)
Sydney Childrens Hosp Randwick, Kids Canc Ctr, Sydney, NSW, Australia.;Univ New South Wales, Sch Clin Med, Discipline Paediat & Child Hlth, Sydney, NSW, Australia.;Univ New South Wales, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia.
Mayoh, Chelsea (författare)
Univ New South Wales, Sch Clin Med, Discipline Paediat & Child Hlth, Sydney, NSW, Australia.;Univ New South Wales, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia.
Mikkel, Sirje (författare)
Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia.
Myrberg, Ida Hed (författare)
Karolinska Institutet
Niinimäki, Riitta (författare)
Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, PEDEGO Res Unit, Oulu, Finland.
Schmiegelow, Kjeld (författare)
Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Fac Med, Copenhagen, Denmark.
Taskinen, Mervi (författare)
Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland.
Vaitkeviciene, Goda (författare)
Vilnius Univ, Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania.
Warnqvist, Anna (författare)
Karolinska Institutet
Wolthers, Benjamin (författare)
Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.
Harila-Saari, Arja H. (författare)
Uppsala universitet,Barnonkologisk och neurologisk forskning
Ranta, Susanna (författare)
Karolinska Institutet
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Karolinska Institutet Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark.;Novo Nordisk Res Ctr Oxford, Oxford, Oxfordshire, England. (creator_code:org_t)
2022-03-31
2020
Engelska.
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
Relaterad länk:
https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.3...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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