New research has identified biomarkers and genetic hallmarks associated with abnormal neurodevelopment following treatment for paediatric acute lymphoblastic leukaemia (ALL).
The study, which followed a cohort of 235 patients, suggests the disease itself may be linked to risk of neurocognitive problems - as well as treatment. The group included 138 long-term survivors. Patients were treated with high-dose intravenous methotrexate sodium and triple intrathecal chemotherapy injections.
Researchers at St Jude Children's Research Hospital, Memphis, Tennessee, USA, said the findings came as "a surprise" as these problems had previously been thought solely to stem from the side-effects of treatments.
According to their estimates between 30 and 40% of survivors develop neurocognitive problems.
The researchers showed that cerebrospinal fluid (CSF) biomarkers for glial damage were elevated at diagnosis and decreased through treatment. Markers of neuronal damage were found to increase during treatment.
The research, published in JAMA Oncology, also suggested a link between brain injury and some genetic variations. Methotrexate treatment was found to increase the risk of leukoencephalopathy by up to 70% in all patients, however carriers of the Val allele in the COMT gene were at an enhanced risk compared to those that carried the Met allele.
Researcher Dr Kevin Krull said: "This was a surprise. Until now, we had not suspected that leukaemia, by itself, or the inflammatory response to the disease, may lead to changes that leave ALL survivors at risk for problems with executive functioning and processing speed later.
"Taken together, the results suggest that survivors' neurocognitive deficits are multifactorial and reflect a complex interaction among genetics, treatment intensity and other factors."
Dr Krull added: "Monitoring CSF biomarkers and screening for genetic mediators of brain injury may help identify and intervene with survivors at risk for neurocognitive problems."
Source: Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia. JAMA Oncology 29 March 2018
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