Impaired neurocognitive functioning 3 months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group

Abstract

Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment.

Patients and methods: A total of 483 children with high-risk ALL, aged 6-12 years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3 months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected.

Results: Data from 390 participants (mean age at diagnosis = 9.2 years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue.

Conclusion: Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3 months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.

Keywords: acute lymphoblastic leukemia; late effects of cancer treatment; psychology.

Figure 1.

Consort Diagram *Potential patients - Aged 6 to < 12 years at time of ALL diagnosis, non-Down syndrome, consented to post induction therapy ^Two patients over 12 years old at diagnosis were consented after the age criteria was relaxed to allow for ages 12–13. Off Therapy/Study before T1 window includes patients who came off in induction and consolidation and submitted no data

Figure 2.

Percentages of impaired Cogstate scores between ALL patients and expected values. Note. One-sided, one sample Z-tests versus normative rates with **p < .01; ***p < .001. ALL = Acute Lymphoblastic Leukemia. WM = Working Memory. Z-statistics for each outcome are as follows: Reaction Time = 6.18, Attention = 7.02, Visual Learning = 2.45, WM= 7.90.

Figure 3.

Percentages of impaired BRIEF scores between ALL patients and expected values. Note. One-sided, one sample Z-tests versus normative rates with ***p < .001. BRIEF = Behavior Rating Inventory of Executive Function. ALL = Acute Lymphoblastic Leukemia. Z-statistics for each outcome are as follows: Behavioral Regulation = 4.56, Metacognition = 1.17, Working Memory = 4.56.