PMID- 37416531
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Association of markers of inflammation on attention and neurobehavioral outcomes 
      in survivors of childhood acute lymphoblastic leukemia.
PG  - 1117096
LID - 10.3389/fonc.2023.1117096 [doi]
LID - 1117096
AB  - BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk 
      of developing cognitive impairment and neurobehavioral symptoms. Inflammation 
      induced by a compromised health status during cancer survivorship is proposed as 
      a pathophysiological mechanism underlying cognitive impairment in cancer 
      survivors. OBJECTIVES: To evaluate the associations of biomarkers of inflammation 
      with attention and neurobehavioral outcomes in survivors of childhood ALL, and to 
      identify clinical factors associated with biomarkers of inflammation in this 
      cohort. METHODS: We recruited patients who were diagnosed with ALL at </= 18 years 
      old and were currently >/=5 years post-cancer diagnosis. The study outcomes were 
      attention (Conners Continuous Performance Test) and self-reported behavioral 
      symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, 
      survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling 
      molecules that are associated with neurodegenerative diseases. The final panel of 
      the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma 
      (IFN-gamma), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory 
      protein-1beta, and tumor necrosis factor-alpha. Biomarker levels were rank-ordered into 
      tertiles based on the sample distribution. Multivariable general linear modeling 
      was used to test for associations between biomarkers and study outcomes in the 
      overall cohort and stratified by gender. RESULTS: This study included 102 
      survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years 
      post-diagnosis). Survivors within top tertiles of IFN-gamma (Estimate =6.74, SE=2.26; 
      P=0.0037) and IL-13 (Estimate =5.10, SE=2.27; P=0.027) demonstrated more 
      inattentiveness. Adjusting for age, gender and treatment, more self-reported 
      thought (Estimate=3.53, SE=1.78; P=0.050) and internalizing problems (Estimate 
      =6.52, SE=2.91; P=0.027) correlated with higher IL-8. Higher levels of IL-13 (RR 
      = 4.58, 95% CI: 1.01-11.10) and TNF-alpha (RR = 1.44, 95% CI: 1.03-4.07) were 
      observed in survivors had developed chronic health conditions (n=26, 25.5%). The 
      stratified analysis showed that association of IFN-gamma with attention was stronger 
      in male survivors than in female survivors. CONCLUSION: Inflammation due to 
      cancer-related late effects may potentially be mechanistic mediators of 
      neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can 
      potentially be applied to assess or monitor the effectiveness of interventions, 
      particularly behavioral interventions, in improving cognitive outcomes in 
      survivors. Future work includes understanding the underlying gender-specific 
      pathophysiology behind functional outcomes in the population.
CI  - Copyright (c) 2023 Cheung, To, Hua, Lee, Chan and Li.
FAU - Cheung, Yin Ting
AU  - Cheung YT
AD  - School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 
      Hong Kong, Hong Kong SAR, China.
FAU - To, Kenneth Kin-Wah
AU  - To KK
AD  - School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 
      Hong Kong, Hong Kong SAR, China.
FAU - Hua, Rong
AU  - Hua R
AD  - School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 
      Hong Kong, Hong Kong SAR, China.
FAU - Lee, Chui Ping
AU  - Lee CP
AD  - School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 
      Hong Kong, Hong Kong SAR, China.
FAU - Chan, Agnes Sui-Ying
AU  - Chan AS
AD  - Neuropsychology Laboratory, Department of Psychology, The Chinese University of 
      Hong Kong, Hong Kong, Hong Kong SAR, China.
FAU - Li, Chi Kong
AU  - Li CK
AD  - Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong 
      Kong, Hong Kong, Hong Kong SAR, China.
AD  - Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, 
      Hong Kong, Hong Kong SAR, China.
AD  - Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong 
      Kong, Hong Kong SAR, China.
LA  - eng
PT  - Journal Article
DEP - 20230621
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10320851
OTO - NOTNLM
OT  - biomarkers
OT  - cognitive function
OT  - inflammation
OT  - late effects
OT  - pediatric leukemia
OT  - psychooncology
OT  - survivors
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/07/07 06:42
MHDA- 2023/07/07 06:43
PMCR- 2023/01/01
CRDT- 2023/07/07 04:08
PHST- 2023/02/24 00:00 [received]
PHST- 2023/05/30 00:00 [accepted]
PHST- 2023/07/07 06:43 [medline]
PHST- 2023/07/07 06:42 [pubmed]
PHST- 2023/07/07 04:08 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1117096 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jun 21;13:1117096. doi: 10.3389/fonc.2023.1117096. eCollection 
      2023.