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Acute central nervo...
Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
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- Anastasopoulou, Stavroula (author)
- Karolinska Institutet
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- Nielsen, Rikke Linnemann (author)
- 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.
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- Als-Nielsen, Bodil (author)
- Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.
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- Banerjee, Joanna (author)
- Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland.
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- Eriksson, Mats A. (author)
- Karolinska Institutet
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- Helenius, Marianne (author)
- Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark.
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- Heyman, Mats M. (author)
- 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.
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- Johannsdottir, Inga Maria (author)
- Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway.
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- Jonsson, Olafur Gisli (author)
- Landspitali Univ Hosp, Dept Pediat, Reykjavik, Iceland.
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- MacGregor, Stuart (author)
- QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
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- Mateos, Marion K. (author)
- 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.
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- Mayoh, Chelsea (author)
- 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.
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- Mikkel, Sirje (author)
- Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia.
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- Myrberg, Ida Hed (author)
- Karolinska Institutet
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- Niinimäki, Riitta (author)
- Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, PEDEGO Res Unit, Oulu, Finland.
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- Schmiegelow, Kjeld (author)
- Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Fac Med, Copenhagen, Denmark.
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- Taskinen, Mervi (author)
- Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland.
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- Vaitkeviciene, Goda (author)
- Vilnius Univ, Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania.
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- Warnqvist, Anna (author)
- Karolinska Institutet
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- Wolthers, Benjamin (author)
- Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.
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- Harila-Saari, Arja H. (author)
- Uppsala universitet,Barnonkologisk och neurologisk forskning
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- Ranta, Susanna (author)
- 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
- English.
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In: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Anastasopoulou, ...
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Nielsen, Rikke L ...
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Als-Nielsen, Bod ...
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Banerjee, Joanna
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Eriksson, Mats A ...
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Helenius, Marian ...
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Heyman, Mats M.
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Johannsdottir, I ...
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Jonsson, Olafur ...
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MacGregor, Stuar ...
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Mateos, Marion K ...
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Mayoh, Chelsea
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Mikkel, Sirje
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Myrberg, Ida Hed
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Niinimäki, Riitt ...
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Schmiegelow, Kje ...
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Taskinen, Mervi
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Vaitkeviciene, G ...
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Warnqvist, Anna
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Wolthers, Benjam ...
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Harila-Saari, Ar ...
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Ranta, Susanna
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- 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 Hematology
- Articles in the publication
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Haematologica
- By the university
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Uppsala University
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Karolinska Institutet