Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

Area of Science:

• Neuroscience
• Oncology
• Radiochemistry

Background:

• Childhood acute lymphocytic leukemia (ALL) often requires high-dose methotrexate (HD-MTX) therapy.
• HD-MTX can cause neurotoxicity, impacting brain function.
• Assessing neurotoxicity is crucial for long-term patient outcomes.

Purpose of the Study:

• To evaluate neurotoxicity in childhood ALL patients treated with HD-MTX.
• To measure changes in regional cerebral metabolic rate of glucose (rCMRGlu) as an indicator of MTX neurotoxicity.
• To correlate rCMRGlu reductions with MTX dosage.

Main Methods:

• Utilized 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to measure rCMRGlu.
• Studied 8 children with ALL treated with HD-MTX (200 mg/kg or 2,000 mg/M2).
• Analyzed correlations between rCMRGlu and total doses of intrathecal MTX (IT-MTX) and systemic HD-MTX.

Main Results:

• Whole-brain rCMRGlu decreased by an average of 21% (P < 0.05) after HD-MTX therapy.
• The most significant reduction (40%) occurred in a patient with central nervous system leukemia receiving maximal MTX doses.
• Reductions in rCMRGlu correlated with total IT-MTX (r=0.717) and HD-MTX (r=0.784) doses (P < 0.05).
• Cerebral cortex, particularly frontal and occipital regions, showed greater rCMRGlu reduction than basal ganglia and white matter.

Conclusions:

• Changes in rCMRGlu are a useful biomarker for detecting accumulated MTX neurotoxicity.
• FDG-PET can identify specific brain regions affected by MTX-induced neurotoxicity.
• This method aids in monitoring and managing potential neurological side effects of HD-MTX therapy in pediatric ALL survivors.