Cerebellar volumes and neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy alone
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摘要Background: Disruption of the glutathione antioxidant pathway by chemotherapy may cause cerebellar volume loss and associated neurocognitive problems in survivors of childhood ALL treated with chemotherapy alone.

Methods: Brain MRIs and neurocognitive tests were obtained in 176 survivors (49% male, mean age at diagnosis 6.8 years, 14.5 years at evaluation). MRIs were also obtained in 82 community controls (57% male, 14.6 years at evaluation). General linear models were used to compare cerebellar volumes between survivors and controls. Among survivors, sex‐stratified multivariate linear models were used to test associations among neurocognitive function,
cerebellar and cortical measurements, serum concentration of dexamethasone, and number of intrathecal injections of methotrexate, hydrocortisone and cytarabine (IT) received, adjusting for age at diagnosis and intracranial volume.

Results: Cerebellar volume was smaller in survivors than controls (p<0.01). In females, smaller cerebellums were associated with more ITs. Controlling for intracranial volume, increased chemotherapy exposures and younger age at diagnosis, smaller cerebellar volume was associated with thinner cortex in the rostral and caudal middle frontal gyri (p’s < 0.0001), precuneus (p <0.0001), and superior frontal areas (p<0.0001) among survivors. Smaller bilateral
cerebellar volumes and more ITs were associated with poorer initiation and cognitive flexibility (p’s<0.05). Smaller cerebellums and higher dexamethasone exposures were associated with poorer organization and planning in female survivors (p's<0.05). Smaller bilateral cerebellar volumes were associated with worse visual processing speed (p=0.02) and poorer working memory was associated with smaller right cerebellar volumes in males (p<0.05). Smaller left cerebellums in males and bilateral cerebellar volumes and higher dexamethasone exposure in females were associated with worse motor processing (p<0.04).

Conclusion: Compared to community controls, long‐term survivors of childhood ALL demonstrated smaller cerebellums associated with cognitive impairment. Results support hypothesis of antioxidant pathway disruption, particularly in females.
著者Nicholas S. Phillips, John O. Glass, Pia Banerjee, Matthew Scoggins, Yin Ting Cheung, Robert J. Ogg, Ching‐Hon Pui, Leslie L. Robison, Wilburn E. Reddick, Melissa M. Hudson, Kevin R. Krull
會議名稱2018 International Cognition and Cancer Task Force Conference

上次更新時間 2018-23-10 於 10:18