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Asparaginase enzyme...
Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia : a NOPHO ALL2008 study
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- Lynggaard, Line Stensig (author)
- Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Aarhus, Denmark.;Aarhus Univ, Dept Clin Med, Aarhus, Denmark.
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- Rank, Cecilie Utke (author)
- Univ Copenhagen, Rigshosp, Dept Haematol, Copenhagen, Denmark.
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- Hansen, Stefan Nygaard (author)
- Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
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- Hojfeldt, Sofie Gottschalk (author)
- Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Aarhus, Denmark.
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- Henriksen, Louise Tram (author)
- Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Aarhus, Denmark.
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- Jarvis, Kirsten Brunsvig (author)
- Oslo Univ Hosp, Dept Paediat Haematol & Oncol, Oslo, Norway.
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- Ranta, Susanna (author)
- Karolinska Institutet
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- Niinimaki, Riitta (author)
- Univ Oulu, Dept Paediat & Adolescent Med, Oulu Univ Hosp, Oulu, Finland.;Univ Oulu, PEDEGO Unit, Oulu, Finland.
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- Harila-Saari, Arja H. (author)
- Uppsala universitet,Institutionen för kvinnors och barns hälsa
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- Wolthers, Benjamin O. (author)
- Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.;Novo Nordisk AS, Soborg, Denmark.
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- Frandsen, Thomas L. (author)
- Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.
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- Heyman, Mats (author)
- Karolinska Institutet
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- Schmiegelow, Kjeld (author)
- Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
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- Albertsen, Birgitte Klug (author)
- Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Aarhus, Denmark.;Aarhus Univ, Dept Clin Med, Aarhus, Denmark.
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Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Aarhus, Denmark;Aarhus Univ, Dept Clin Med, Aarhus, Denmark. Univ Copenhagen, Rigshosp, Dept Haematol, Copenhagen, Denmark. (creator_code:org_t)
- 2022-01-04
- 2022
- English.
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 138-147
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Lynggaard, Line ...
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Rank, Cecilie Ut ...
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Hansen, Stefan N ...
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Hojfeldt, Sofie ...
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Henriksen, Louis ...
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Jarvis, Kirsten ...
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Ranta, Susanna
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Niinimaki, Riitt ...
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Harila-Saari, Ar ...
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Wolthers, Benjam ...
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Frandsen, Thomas ...
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Heyman, Mats
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Schmiegelow, Kje ...
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Albertsen, Birgi ...
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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 Pediatrics
- Articles in the publication
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Blood Advances
- By the university
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Uppsala University
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Karolinska Institutet