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Neurocognitive outcomes in survivors of ALL : Risk patterns and individual profiles in a single-protocol cohort

Nordhjem, Barbara Johanne Thomas ; Andrés-Jensen, Liv ; Christensen, Kristian Mielke ; Helenius, Marianne ; Thomsen, Birthe Lykke ; Olsson, Ingrid Tonning LU orcid ; Larsen, Hanne Bækgaard and Hjalgrim, Lisa Lyngsie (2026) In Journal of the International Neuropsychological Society
Abstract

Objective: Increasing survival probabilities among children and young adults with acute lymphoblastic leukemia (ALL) have led to a growing population at risk for long-term neurocognitive sequelae. This study investigated cognitive functioning among individuals treated for ALL under the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol in Eastern Denmark, including performance across multiple domains and associations with age at diagnosis, sex, time since end of treatment, hematopoietic stem cell transplantation (HSCT), and neurotoxic events during treatment. Method: Eighty-three survivors of ALL diagnosed before age 25 underwent neurocognitive testing at a median of 7.24 years post-treatment (interquartile range:... (More)

Objective: Increasing survival probabilities among children and young adults with acute lymphoblastic leukemia (ALL) have led to a growing population at risk for long-term neurocognitive sequelae. This study investigated cognitive functioning among individuals treated for ALL under the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol in Eastern Denmark, including performance across multiple domains and associations with age at diagnosis, sex, time since end of treatment, hematopoietic stem cell transplantation (HSCT), and neurotoxic events during treatment. Method: Eighty-three survivors of ALL diagnosed before age 25 underwent neurocognitive testing at a median of 7.24 years post-treatment (interquartile range: 4.20–8.78). Performance was measured as age-standardized Z scores derived from normative data. Impairment was defined as Z ≤ −1.3 and severe impairment as Z ≤ −2.0. Multiple linear regression was used to investigate associations between cognitive outcomes and clinical risk factors. Results: Average performance was generally comparable to norms, but at least 38.6% of participants showed severe impairment in one or more domains, and at least 12% in two or more. Younger age at diagnosis was associated with poorer processing speed, executive functions, and non-verbal reasoning, while HSCT was associated with poorer processing speed and non-verbal reasoning. Conclusions: Although average performance of the participants was generally comparable to norms, a notable proportion exhibited multi-domain, severe cognitive impairment. Associations with age at diagnosis and HSCT indicate potential for risk-stratified cognitive monitoring and targeted interventions.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Acute lymphoblastic leukemia, cancer survivors, cognition disorders, hematopoietic stem cell transplantation, neuropsychological tests, young adult
in
Journal of the International Neuropsychological Society
publisher
Cambridge University Press
external identifiers
  • pmid:41657016
  • scopus:105030037701
ISSN
1355-6177
DOI
10.1017/S1355617726101829
language
English
LU publication?
yes
id
c5f22f7b-8393-453a-81a5-020bb3b7eb52
date added to LUP
2026-03-02 13:52:48
date last changed
2026-05-26 02:26:37
@article{c5f22f7b-8393-453a-81a5-020bb3b7eb52,
  abstract     = {{<p>Objective: Increasing survival probabilities among children and young adults with acute lymphoblastic leukemia (ALL) have led to a growing population at risk for long-term neurocognitive sequelae. This study investigated cognitive functioning among individuals treated for ALL under the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol in Eastern Denmark, including performance across multiple domains and associations with age at diagnosis, sex, time since end of treatment, hematopoietic stem cell transplantation (HSCT), and neurotoxic events during treatment. Method: Eighty-three survivors of ALL diagnosed before age 25 underwent neurocognitive testing at a median of 7.24 years post-treatment (interquartile range: 4.20–8.78). Performance was measured as age-standardized Z scores derived from normative data. Impairment was defined as Z ≤ −1.3 and severe impairment as Z ≤ −2.0. Multiple linear regression was used to investigate associations between cognitive outcomes and clinical risk factors. Results: Average performance was generally comparable to norms, but at least 38.6% of participants showed severe impairment in one or more domains, and at least 12% in two or more. Younger age at diagnosis was associated with poorer processing speed, executive functions, and non-verbal reasoning, while HSCT was associated with poorer processing speed and non-verbal reasoning. Conclusions: Although average performance of the participants was generally comparable to norms, a notable proportion exhibited multi-domain, severe cognitive impairment. Associations with age at diagnosis and HSCT indicate potential for risk-stratified cognitive monitoring and targeted interventions.</p>}},
  author       = {{Nordhjem, Barbara Johanne Thomas and Andrés-Jensen, Liv and Christensen, Kristian Mielke and Helenius, Marianne and Thomsen, Birthe Lykke and Olsson, Ingrid Tonning and Larsen, Hanne Bækgaard and Hjalgrim, Lisa Lyngsie}},
  issn         = {{1355-6177}},
  keywords     = {{Acute lymphoblastic leukemia; cancer survivors; cognition disorders; hematopoietic stem cell transplantation; neuropsychological tests; young adult}},
  language     = {{eng}},
  publisher    = {{Cambridge University Press}},
  series       = {{Journal of the International Neuropsychological Society}},
  title        = {{Neurocognitive outcomes in survivors of ALL : Risk patterns and individual profiles in a single-protocol cohort}},
  url          = {{http://dx.doi.org/10.1017/S1355617726101829}},
  doi          = {{10.1017/S1355617726101829}},
  year         = {{2026}},
}