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

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Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes. / Anastasopoulou, Stavroula; Nielsen, Rikke Linnemann; Als-Nielsen, Bodil; Banerjee, Joanna; Eriksson, Mats A.; Helenius, Marianne; Heyman, Mats M.; Johannsdottir, Inga Maria; Jonsson, Olafur Gisli; MacGregor, Stuart; Mateos, Marion K.; Mayoh, Chelsea; Mikkel, Sirje; Myrberg, Ida Hed; Niinimäki, Riitta; Schmiegelow, Kjeld; Taskinen, Mervi; Vaitkeviciene, Goda; Warnqvist, Anna; Wolthers, Benjamin; Harila-Saari, Arja; Ranta, Susanna.

In: Haematologica, Vol. 107, No. 10, 2022, p. 2318-2328.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Anastasopoulou, S, Nielsen, RL, Als-Nielsen, B, Banerjee, J, Eriksson, MA, Helenius, M, Heyman, MM, Johannsdottir, IM, Jonsson, OG, MacGregor, S, Mateos, MK, Mayoh, C, Mikkel, S, Myrberg, IH, Niinimäki, R, Schmiegelow, K, Taskinen, M, Vaitkeviciene, G, Warnqvist, A, Wolthers, B, Harila-Saari, A & Ranta, S 2022, 'Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes', Haematologica, vol. 107, no. 10, pp. 2318-2328. https://doi.org/10.3324/haematol.2021.280016

APA

Anastasopoulou, S., Nielsen, R. L., Als-Nielsen, B., Banerjee, J., Eriksson, M. A., Helenius, M., Heyman, M. M., Johannsdottir, I. M., Jonsson, O. G., MacGregor, S., Mateos, M. K., Mayoh, C., Mikkel, S., Myrberg, I. H., Niinimäki, R., Schmiegelow, K., Taskinen, M., Vaitkeviciene, G., Warnqvist, A., ... Ranta, S. (2022). Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes. Haematologica, 107(10), 2318-2328. https://doi.org/10.3324/haematol.2021.280016

Vancouver

Anastasopoulou S, Nielsen RL, Als-Nielsen B, Banerjee J, Eriksson MA, Helenius M et al. Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes. Haematologica. 2022;107(10):2318-2328. https://doi.org/10.3324/haematol.2021.280016

Author

Anastasopoulou, Stavroula ; Nielsen, Rikke Linnemann ; Als-Nielsen, Bodil ; Banerjee, Joanna ; Eriksson, Mats A. ; Helenius, Marianne ; Heyman, Mats M. ; Johannsdottir, Inga Maria ; Jonsson, Olafur Gisli ; MacGregor, Stuart ; Mateos, Marion K. ; Mayoh, Chelsea ; Mikkel, Sirje ; Myrberg, Ida Hed ; Niinimäki, Riitta ; Schmiegelow, Kjeld ; Taskinen, Mervi ; Vaitkeviciene, Goda ; Warnqvist, Anna ; Wolthers, Benjamin ; Harila-Saari, Arja ; Ranta, Susanna. / Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes. In: Haematologica. 2022 ; Vol. 107, No. 10. pp. 2318-2328.

Bibtex

@article{c366de7a211c44f6801b9e9dfa75b8af,
title = "Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes",
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.",
author = "Stavroula Anastasopoulou and Nielsen, {Rikke Linnemann} and Bodil Als-Nielsen and Joanna Banerjee and Eriksson, {Mats A.} and Marianne Helenius and Heyman, {Mats M.} and Johannsdottir, {Inga Maria} and Jonsson, {Olafur Gisli} and Stuart MacGregor and Mateos, {Marion K.} and Chelsea Mayoh and Sirje Mikkel and Myrberg, {Ida Hed} and Riitta Niinim{\"a}ki and Kjeld Schmiegelow and Mervi Taskinen and Goda Vaitkeviciene and Anna Warnqvist and Benjamin Wolthers and Arja Harila-Saari and Susanna Ranta",
note = "Publisher Copyright: {\textcopyright} 2022 Ferrata Storti Foundation Published under a CC BY-NC license.",
year = "2022",
doi = "10.3324/haematol.2021.280016",
language = "English",
volume = "107",
pages = "2318--2328",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "10",

}

RIS

TY - JOUR

T1 - Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia

T2 - phenotypes, risk factors and genotypes

AU - Anastasopoulou, Stavroula

AU - Nielsen, Rikke Linnemann

AU - Als-Nielsen, Bodil

AU - Banerjee, Joanna

AU - Eriksson, Mats A.

AU - Helenius, Marianne

AU - Heyman, Mats M.

AU - Johannsdottir, Inga Maria

AU - Jonsson, Olafur Gisli

AU - MacGregor, Stuart

AU - Mateos, Marion K.

AU - Mayoh, Chelsea

AU - Mikkel, Sirje

AU - Myrberg, Ida Hed

AU - Niinimäki, Riitta

AU - Schmiegelow, Kjeld

AU - Taskinen, Mervi

AU - Vaitkeviciene, Goda

AU - Warnqvist, Anna

AU - Wolthers, Benjamin

AU - Harila-Saari, Arja

AU - Ranta, Susanna

N1 - Publisher Copyright: © 2022 Ferrata Storti Foundation Published under a CC BY-NC license.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.3324/haematol.2021.280016

DO - 10.3324/haematol.2021.280016

M3 - Journal article

C2 - 35354251

AN - SCOPUS:85138584864

VL - 107

SP - 2318

EP - 2328

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 10

ER -

ID: 329283335