Chemotherapy-related changes in central nervous system phospholipids and neurocognitive function in childhood acute lymphoblastic leukemia

Abstract

Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction (p = 0.03) and consolidation (p = 0.04), while lysophosphatidylcholine (LPC) increased following induction (p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year (p < 0.001), 2 years (p = 0.001) and 3 years (p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory (p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity.

Keywords::

• Cerebral spinal fluid
• childhood leukemia
• neurocognitive
• phospholipids

Acknowledgements

The authors acknowledge NIH grants NR04905 and HD37816. Support was also provided to K.R.K. by MH085849, CA21765 and by the American Lebanese-Syrian Associated Charities (ALSAC).

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.