By Lynda Williams, medwireNews Reporter
Children with a new diagnosis of acute lymphoblastic leukaemia (ALL) who receive intensified central nervous system (CNS)-directed therapy have an increased risk of neurocognitive deficits, indicates research published in the Journal of Clinical Oncology.
“Our findings can be used to inform risk-directed neurocognitive screening and intervention that is feasible across settings, thus promoting evidence-based care for patients and families”, write Lisa Jacola and co-authors, from St Jude Children’s Research Hospital in Memphis, Tennessee, USA.
The team explains that early intensification of the Total 16 regimen of triple intrathecal therapy (ITT; methotrexate, hydrocortisone and cytarabine) has been shown to improve CNS disease control in children at high risk of relapse but the long-term impact on neurocognitive outcomes is unknown.
To investigate, the team collated neurocognitive test results from the end of treatment for 400 participants in the Total 16 trial conducted between 2007 and 2017; the average age at ALL diagnosis was 7.05 years and the average age at testing was 9.67 years.
CNS-directed therapy was given throughout remission induction and consolidation treatment, with 70 of the 194 patients at low risk of relapse given an intensified ITT regimen (≥21 vs 13 or 19 doses), as were 81 of the 206 patients at standard-to-high risk of relapse (≥27 vs 16 or 25 doses).
Overall, the Total 16 participants showed a significant reduction in estimated IQ, attention, working memory, processing speed, executive function, new memory formation, fine motor speed and maths compared with age-based norms for these measures.
And caregivers confirmed that patients were more likely to be at risk for problems with attention, executive function and adaptive skills.
Among children with a low risk of relapse, there was no significant difference in neurocognitive measures between those who did and did not receive intensified ITT.
But among children with a standard-to-high risk of relapse, receipt of intensified ITT was associated with a significant decrease in working memory, slower fine motor speed, and greater inattention and executive dysfunction.
Indeed, “elevated risk for neurocognitive impairment was evident across domains” and “most prominent” in working memory, fine motor speed and learning or memory, Jacola and co-authors write.
And among girls at moderate-to-high risk of relapse, intensified ITT was associated with significantly poorer working memory compared with standard ITT.
However, the researchers also found that children with public or no insurance had worse neurocognitive outcomes than those with private insurance, and therefor highlight the need for research to also “examine the role of social economic status on the association between treatment-related alterations in brain development and neurocognitive outcomes.”
While emphasizing the need for neurocognitive monitoring during treatment and beyond, the researchers acknowledge that “operationalizing this recommendation is challenging in centers with varying levels of resources, and not all survivors may need comprehensive evaluation.”
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J Clin Oncol 2022; doi:10.1200/JCO.22.00263