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

Autor:	Anastasopoulou S; Astrid 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., Nielsen RL; Department 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., Als-Nielsen B; Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen., Banerjee J; Division of Pediatric Hematology and Oncology and Stem Cell Transplantation, Helsinki University Hospital and Helsinki University, Helsinki., Eriksson MA; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm., Helenius M; Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kgs. Lyngby., Heyman MM; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm., Johannsdottir IM; Department of Pediatric Hematology/Oncology, Oslo University Hospital, Oslo, Norway., Jonsson OG; Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland., MacGregor S; QIMR Berghofer Medical Research Institute, Brisbane., Mateos MK; Kids 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., Mayoh C; 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., Mikkel S; Department of Hematology and Oncology, University of Tartu, Tartu., Myrberg IH; Childhood 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., Niinimäki R; Department of Children and Adolescents, Oulu University Hospital and University of Oulu, PEDEGO Research Unit, Oulu., Schmiegelow K; Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen., Taskinen M; Division of Pediatric Hematology and Oncology and Stem Cell Transplantation, Helsinki University Hospital and Helsinki University, Helsinki., Vaitkeviciene G; Children's Hospital, affiliate of Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius., Warnqvist A; Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm., Wolthers B; Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen., Harila-Saari A; Department of Women's and Children's Health, Uppsala University, Uppsala., Ranta S; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2022 Oct 01; Vol. 107 (10), pp. 2318-2328. Date of Electronic Publication: 2022 Oct 01.
DOI:	10.3324/haematol.2021.280016
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu