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Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia: a NOPHO ALL2008 study

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Harvard

Lynggaard, LS, Rank, CU, Hansen, SN, Gottschalk Højfeldt, S, Henriksen, LT, Jarvis, KB, Ranta, S, Niinimäki, R, Harila-Saari, A, Wolthers, BO, Frandsen, TL, Heyman, M, Schmiegelow, K & Albertsen, BK 2022, 'Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia: a NOPHO ALL2008 study', Blood advances, bind 6, nr. 1, s. 138-147. https://doi.org/10.1182/bloodadvances.2021005631

APA

Lynggaard, L. S., Rank, C. U., Hansen, S. N., Gottschalk Højfeldt, S., Henriksen, L. T., Jarvis, K. B., Ranta, S., Niinimäki, R., Harila-Saari, A., Wolthers, B. O., Frandsen, T. L., Heyman, M., Schmiegelow, K., & Albertsen, B. K. (2022). Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia: a NOPHO ALL2008 study. Blood advances, 6(1), 138-147. https://doi.org/10.1182/bloodadvances.2021005631

CBE

Lynggaard LS, Rank CU, Hansen SN, Gottschalk Højfeldt S, Henriksen LT, Jarvis KB, Ranta S, Niinimäki R, Harila-Saari A, Wolthers BO, Frandsen TL, Heyman M, Schmiegelow K, Albertsen BK. 2022. Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia: a NOPHO ALL2008 study. Blood advances. 6(1):138-147. https://doi.org/10.1182/bloodadvances.2021005631

MLA

Vancouver

Author

Lynggaard, Line Stensig ; Rank, Cecilie Utke ; Hansen, Stefan Nygaard ; Gottschalk Højfeldt, Sofie ; Henriksen, Louise Tram ; Jarvis, Kirsten Brunsvig ; Ranta, Susanna ; Niinimäki, Riitta ; Harila-Saari, Arja ; Wolthers, Benjamin Ole ; Frandsen, Thomas Leth ; Heyman, Mats ; Schmiegelow, Kjeld ; Albertsen, Birgitte Klug. / Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia : a NOPHO ALL2008 study. I: Blood advances. 2022 ; Bind 6, Nr. 1. s. 138-147.

Bibtex

@article{d2ae9995e4d2462397669457591b0aa8,
title = "Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia: a NOPHO ALL2008 study",
abstract = "Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with ≥2 blood samples for AEA measurement drawn 14 ± 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.",
author = "Lynggaard, {Line Stensig} and Rank, {Cecilie Utke} and Hansen, {Stefan Nygaard} and {Gottschalk H{\o}jfeldt}, Sofie and Henriksen, {Louise Tram} and Jarvis, {Kirsten Brunsvig} and Susanna Ranta and Riitta Niinim{\"a}ki and Arja Harila-Saari and Wolthers, {Benjamin Ole} and Frandsen, {Thomas Leth} and Mats Heyman and Kjeld Schmiegelow and Albertsen, {Birgitte Klug}",
note = "Copyright {\textcopyright} 2021 American Society of Hematology.",
year = "2022",
month = jan,
day = "11",
doi = "10.1182/bloodadvances.2021005631",
language = "English",
volume = "6",
pages = "138--147",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "1",

}

RIS

TY - JOUR

T1 - Asparaginase Enzyme Activity Levels and Toxicity in Childhood Acute Lymphoblastic Leukemia

T2 - a NOPHO ALL2008 study

AU - Lynggaard, Line Stensig

AU - Rank, Cecilie Utke

AU - Hansen, Stefan Nygaard

AU - Gottschalk Højfeldt, Sofie

AU - Henriksen, Louise Tram

AU - Jarvis, Kirsten Brunsvig

AU - Ranta, Susanna

AU - Niinimäki, Riitta

AU - Harila-Saari, Arja

AU - Wolthers, Benjamin Ole

AU - Frandsen, Thomas Leth

AU - Heyman, Mats

AU - Schmiegelow, Kjeld

AU - Albertsen, Birgitte Klug

N1 - Copyright © 2021 American Society of Hematology.

PY - 2022/1/11

Y1 - 2022/1/11

N2 - Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with ≥2 blood samples for AEA measurement drawn 14 ± 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.

AB - Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with ≥2 blood samples for AEA measurement drawn 14 ± 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.

U2 - 10.1182/bloodadvances.2021005631

DO - 10.1182/bloodadvances.2021005631

M3 - Journal article

C2 - 34625787

VL - 6

SP - 138

EP - 147

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 1

ER -

ID: 68508687