Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.

Sofie G Højfeldt; Benjamin O Wolthers; Morten Tulstrup; Jonas Abrahamsson; Ramneek Gupta; Arja Harila-Saari; Mats Heyman; Louise T Henriksen; Òlafur G Jónsson; Päivi M Lähteenmäki; Bendik Lund; Kaie Pruunsild; Goda Vaitkeviciene; Kjeld Schmiegelow; Birgitte K Albertsen

doi:10.1111/bjh.15660

Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.

Sofie G Højfeldt, Benjamin O Wolthers, Morten Tulstrup, Jonas Abrahamsson, Ramneek Gupta, Arja Harila-Saari, Mats Heyman, Louise T Henriksen, Òlafur G Jónsson, Päivi M Lähteenmäki, Bendik Lund, Kaie Pruunsild, Goda Vaitkeviciene, Kjeld Schmiegelow, Birgitte K Albertsen

Landspitali - The National University Hospital of Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10

Original language	English
Journal	British Journal of Haematology
DOIs	https://doi.org/10.1111/bjh.15660
Publication status	Published - 1 Feb 2019

Other keywords

PEG-asparaginase
genome-wide association study
hypersensitivity
paediatric acute lymphoblastic leukaemia
Bráðahvítblæði
Lyfjameðferð
Lyf
Ofnæmi
Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hypersensitivity

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10.1111/bjh.15660

https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.15660

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Højfeldt, S. G., Wolthers, B. O., Tulstrup, M., Abrahamsson, J., Gupta, R., Harila-Saari, A., Heyman, M., Henriksen, L. T., Jónsson, Ò. G., Lähteenmäki, P. M., Lund, B., Pruunsild, K., Vaitkeviciene, G., Schmiegelow, K., & Albertsen, B. K. (2019). Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. British Journal of Haematology. https://doi.org/10.1111/bjh.15660

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title = "Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.",

abstract = "Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10",

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author = "H{\o}jfeldt, {Sofie G} and Wolthers, {Benjamin O} and Morten Tulstrup and Jonas Abrahamsson and Ramneek Gupta and Arja Harila-Saari and Mats Heyman and Henriksen, {Louise T} and J{\'o}nsson, {{\`O}lafur G} and L{\"a}hteenm{\"a}ki, {P{\"a}ivi M} and Bendik Lund and Kaie Pruunsild and Goda Vaitkeviciene and Kjeld Schmiegelow and Albertsen, {Birgitte K}",

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doi = "10.1111/bjh.15660",

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Højfeldt, SG, Wolthers, BO, Tulstrup, M, Abrahamsson, J, Gupta, R, Harila-Saari, A, Heyman, M, Henriksen, LT, Jónsson, ÒG, Lähteenmäki, PM, Lund, B, Pruunsild, K, Vaitkeviciene, G, Schmiegelow, K & Albertsen, BK 2019, 'Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.', British Journal of Haematology. https://doi.org/10.1111/bjh.15660

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T1 - Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.

AU - Højfeldt, Sofie G

AU - Wolthers, Benjamin O

AU - Tulstrup, Morten

AU - Abrahamsson, Jonas

AU - Gupta, Ramneek

AU - Harila-Saari, Arja

AU - Heyman, Mats

AU - Henriksen, Louise T

AU - Jónsson, Òlafur G

AU - Lähteenmäki, Päivi M

AU - Lund, Bendik

AU - Pruunsild, Kaie

AU - Vaitkeviciene, Goda

AU - Schmiegelow, Kjeld

AU - Albertsen, Birgitte K

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10

AB - Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10

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KW - genome-wide association study

KW - hypersensitivity

KW - paediatric acute lymphoblastic leukaemia

KW - Bráðahvítblæði

KW - Lyfjameðferð

KW - Lyf

KW - Ofnæmi

KW - Asparaginase

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Hypersensitivity

KW - PEG-asparaginase

KW - genome-wide association study

KW - hypersensitivity

KW - paediatric acute lymphoblastic leukaemia

KW - Bráðahvítblæði

KW - Lyfjameðferð

KW - Lyf

KW - Ofnæmi

KW - Asparaginase

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Hypersensitivity

U2 - 10.1111/bjh.15660

DO - 10.1111/bjh.15660

M3 - Article

C2 - 30450575

SN - 1365-2141

JO - British Journal of Haematology

JF - British Journal of Haematology

ER -

Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.

Abstract

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