Longitudinal Trajectories of Neurocognitive Functioning in Childhood Acute Lymphoblastic Leukemia

Abstract

Objective Children 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. Methods There 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. Results Within 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. Conclusions Most 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.

Leukemia and sickle cell disease.

“…Specifically, survivors of standard-risk ALL exhibit impairments in flexibility, initiation, working memory, and emotional control (Walsh et al, 2015). Longitudinal assessments suggest persistent impairments, despite some improvements in sustained attention 2 years off therapy Partanen et al, 2021). Although not all survivors experience chronic difficulties, average sustained attention remains below age expectations from induction to post therapy, with survivors demonstrating the greatest difficulties with executive functions at the end of therapy .…”

“…Interestingly, patients who experienced bacteremia but not sepsis displayed comparable performance to those without bacteremia or sepsis. Sepsis has also been associated with sustained attention problems following treatment completion (Partanen et al, 2021) Leukoencephalopathy. As a common complication of chemotherapy, leukoencephalopathy is linked with white matter integrity.…”

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons

“…65 In another retrospective study, children who had experienced bacteremic sepsis during therapy for ALL had significantly worse neurocognitive function in multiple domains (especially executive function and attention) at around 5 years after completion of treatment compared to patients treated in the same time period who did not have sepsis. 63,64 This is especially important as neurocognitive damage is second only to death as a concern for parents and caregivers. 66,67 Cancer survivors have a much greater burden of other chronic health conditions, many in domains that can be acutely compromised by infection, such as renal, cardiac, and pulmonary systems, but whether infection increases, the risk of these is unknown.…”

“…Prevention of infection by fluoroquinolone might also reduce the risk of long‐term complications 63–65 . In a retrospective study, children who had bacterial BSI during therapy for ALL were more likely to develop osteonecrosis, a common and potentially disabling complication 65 .…”

“…In a retrospective study, children who had bacterial BSI during therapy for ALL were more likely to develop osteonecrosis, a common and potentially disabling complication 65 . In another retrospective study, children who had experienced bacteremic sepsis during therapy for ALL had significantly worse neurocognitive function in multiple domains (especially executive function and attention) at around 5 years after completion of treatment compared to patients treated in the same time period who did not have sepsis 63,64 . This is especially important as neurocognitive damage is second only to death as a concern for parents and caregivers 66,67 .…”