Dataset Information

Characterization of Leukoencephalopathy and Association With Later Neurocognitive Performance in Pediatric Acute Lymphoblastic Leukemia.

ABSTRACT:

Objectives

The most common form of pediatric cancer is acute lymphoblastic leukemia (ALL). Magnetic resonance (MR) neuroimaging studies have revealed leukoencephalopathy (LE) in pediatric ALL, but the impact of LE on long-term neurocognitive performance remains unknown. This study aims to objectively characterize the prevalence, extent, and intensity of LE, and their association with later neurocognitive performance.

Materials and methods

Pediatric patients (N = 377) treated for ALL without irradiation underwent MR neuroimaging at 4 time points throughout therapy (end of remission induction [MR1], end of consolidation [MR2], and week 31 [MR3] and week 120 [end therapy, MR4] of continuation treatment) and neurocognitive evaluations at the end of therapy and 2 years later. Generalized estimation equation models with logit link were developed to explore the association between LE prevalence and extent with time points throughout therapy, age at diagnosis (≤5 years or >5 years), treatment risk arm (low risk or standard/high risk), and sex. General linear models were also developed to investigate the association between neuroimaging metrics during treatment and neurocognitive performance at 2-year follow-up.

Results

The prevalence of LE was greatest (22.8%, 74/324) after consolidation therapy. The prevalence of LE increased at MR2 relative to MR1 regardless of treatment risk arm (both P's < 0.001), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.013). The extent of white matter affected also increased at MR2 relative to MR1 regardless of treatment risk arm (standard/high risk, P < 0.001; low risk, P = 0.004), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.001). Quantitative relaxation rates were significantly longer in LE compared with that in normal-appearing white matter in the same examination (T1, P < 0.001; T2, P < 0.001). The LE prevalence early in therapy was associated with increased parent ratings of conduct problems (P = 0.039) and learning difficulties (P = 0.036) at 2-year follow-up compared with that at the end of therapy. A greater extent of LE early in therapy was associated with decreasing performance on a measure of processing speed (P = 0.003) from the end of therapy to 2-year follow-up. A larger extent of LE at the end of therapy was associated with decreased performance in reading (P = 0.004), spelling (P = 0.003), and mathematics (P = 0.019) at 2-year follow-up and increasing problems with attention (omissions, P = 0.045; β, P = 0.015) and memory (list A total recall, P = 0.010) at 2-year follow-up compared with that at the end of therapy.

Conclusions

In this large cohort of pediatric patients treated for ALL without irradiation, asymptomatic LE during therapy can be seen in almost a quarter of patients, involves as much as 10% of the white matter volume, and is associated with decreasing neurocognitive performance, increasing parent reports of conduct problems, and learning difficulties in survivors.

SUBMITTER: Pryweller JR

PROVIDER: S-EPMC8059361 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveChildren with acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits, and examining individual variability is essential to understand these risks. This study evaluated latent longitudinal trajectories and risk factors of neurocognitive outcomes in childhood ALL.MethodsThere were 233 participants with ALL who were enrolled on a phase 3, risk-stratified chemotherapy-only clinical trial (NCT00137111) and who completed protocol-directed neurocognitive assessments [47.6% female, mean (SD) = 6.6 (3.7) years]. Measures of sustained attention, learning/memory, and parent ratings of attention were completed during and after treatment. Longitudinal latent class analyses were used to classify participants into distinct trajectories. Logistic regression was used to identify predictors of class membership.ResultsWithin the overall group, attention performance was below age expectations across time (Conners Continuous Performance Test detectability/variability, p < 0.01); memory performance and parent ratings were below expectations at later phases (California Verbal Learning Test learning slope, p < 0.05; Conners Parent Rating Scale, Revised attention/learning, p < 0.05). Most participants (80-89%) had stable neurocognitive profiles; smaller groups showed declining (3-6%) or improving (3-11%) trajectories. Older age (p = 0.020), female sex (p = 0.018), and experiencing sepsis (p = 0.047) were associated with greater attention problems over time. Lower baseline IQ was associated with improved memory (p = 0.035) and fewer ratings of attention problems (p = 0.013) over time.ConclusionsMost patients with ALL have stable neurocognitive profiles. Smaller groups have significant impairments shortly after diagnosis or have worsening performance over time. A tiered assessment approach, which includes consideration of individual and clinical risk factors, may be useful for monitoring neurocognitive functioning during treatment and survivorship.