Survivors of childhood leukemia (ALL) who are treated with chemotherapy develop poor cognitive skills (e.g. attention, speed of thinking, reasoning). These poor cognitive skills cause problems with school, work and peer interactions. The survivors also display abnormalities on brain imaging. We demonstrated that fluid collected during a spinal tap (i.e. cerebrospinal fluid [CSF]) contained markers of brain injury. However, our initial study was too focused on specific brain cells. We could not identify the cause of the brain injury. Thus, we want to conduct another study to examine many more protein markers before and after chemotherapy treatment.
We will use an advanced process to identify over 4,000 proteins in the CSF. This will permit us to determine the cause of the brain injury. We will compare the proteins to sex and age of the survivors. We will also compare the proteins to the treatments the survivors got. Finally, we will compare the change in proteins to brain imaging and cognitive testing.
CSF samples from a recently completed trial have been collected and frozen at −80°C so they will not decay. The brain imaging and cognitive testing is currently being completed as part of an institutionally funded protocol. For the current project, we will process the CSF samples and link them to adverse events and clinical outcomes.
With this comprehensive approach, we will identify which survivors are at greatest risk, and identify targets to prevent brain injury in future clinical trials.