Subcortical brain volumes and neurocognitive function in survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy-only.

Abstract

10517 Background: Brain deep grey nuclei and glucocorticoid receptor rich hippocampal subregions may be sensitive to neurotoxic effects of chemotherapy-only protocols for childhood ALL and associated with neurocognitive problems in long-term survivors. Methods: Brain MRIs and neurocognitive tests were obtained on 176 survivors (49% male, mean [range] age at diagnosis 6.8 [1-18] years, 14.5 [8-27] years at evaluation). MRI’s were also obtained on 82 healthy community controls (57% male, 13.8 [8-26] years at evaluation). General linear models were used to compare subcortical brain volumes between survivors and controls. Among survivors, gender stratified multivariable linear models were used to test associations between subcortical volumes, and serum concentration of dexamethasone (DEX) and high-dose methotrexate (HDMTX), adjusting for age at diagnosis, and intracranial volume (ICV). Volumes were also compared to neurocognitive tests. Results: Survivors had smaller volumes in bilateral thalami (p’s < 0.05) and hippocampal subregions (p’s < 0.001) compared to controls. After controlling for ICV, HDMTX exposure and younger age at diagnosis were associated with smaller bilateral thalami in male survivors (p’s < 0.05). DEX was associated with a smaller right thalamus in males (p = 0.04). Smaller hippocampi in both males and females were associated with younger age at diagnosis (p’s < 0.01). Smaller left thalamus was associated with worse verbal fluency scores in all survivors (p’s < 0.05). Smaller bilateral thalami and hippocampal subregions in girls were associated with worse processing speed, inhibition and cognitive flexibility; poor memory span correlated with smaller left CA1 and right thalamus volumes (all p’s < 0.05). Smaller bilateral thalami and right hippocampal subregions, in girls, correlated with slower processing speed (p’s < 0.05). In males, smaller left fimbria volume was correlated with poor attention (p = 0.03). Conclusions: ALL survivors have significantly smaller thalamic and hippocampal volumes compared to healthy community controls. In survivors, smaller volumes correlate with worse cognitive performance.