Dr Christina Halsey, University of Glasgow
Children with leukaemia and other cancers receive chemotherapy targeted to the brain to prevent disease recurrence at this site. This is a vital part of treatment but can cause damage to normal brain tissue, leading to reductions in IQ, attention span and working memory. Dr Halsey and colleagues are developing new tests to help predict which children are at increased risk of these brain-related complications. These tests may also be used to discover new ways of treating or preventing this devastating complication of childhood cancer treatment.
Amount of grant: £166,088 | Date of award: June 2014
Children with cancer are given combinations of chemotherapy drugs in high doses. Those with leukaemia and some other cancers are given chemotherapy specifically targeted to the brain in order to prevent recurrence at this site. Whilst these drugs give young patients the best chance of surviving their cancer, they are highly toxic and can damage developing brains.
Children treated with chemotherapy can show reduced IQ, reduced attention span and impaired memory. Recent research suggests that these problems can continue to develop throughout adulthood.
Currently there is no way to predict which children will develop these neurological problems and there are no treatments to prevent or reduce them. There is an urgent need, therefore, to determine what causes some children to develop these problems and to understand which children are at risk so that new targeted therapies can be designed.
In this UK-wide study, the team will recruit 200 children and young people from amongst participants in the current national childhood acute lymphoblastic leukaemia trial - UKALL 2011.
Patients will complete a set of simple computer games that have been designed to test ability to solve problems, reaction times and attention span. Test results will be analysed to see if subtle early changes in ability to perform these tasks predict long-term problems with learning and memory.
The team will also collect leftover samples of blood and cerebrospinal fluid (CSF), taken routinely during leukaemia treatment. The blood samples will be analysed for genetic differences in the way that different children’s brains deal with chemotherapy or repair damage, which may explain why only some children suffer brain side-effects. The CSF will be analysed to assess whether children with brain side-effects have higher levels of toxins or breakdown products of chemotherapy in the CSF which could potentially be used as diagnostic tests or to develop antidotes in the future.
About the research team
Dr Christina Halsey is a Consultant Paediatric Haematologist at Glasgow’s Royal Hospital for Sick Children and holds a Clinical Senior Lecturer post in childhood acute lymphoblastic leukaemia at the University of Glasgow. Her main research interest is in the development of better treatments for brain involvement in childhood ALL.
Dr Halsey has assembled a large research team comprising scientists, consultant haemato-oncologists, neurologists and neuro-radiologists.
The team is led by Dr Halsey, along with two co-investigators, Dr Frederick van Delft of Newcastle University and Dr Peter Cole of Albert Einstein College of Medicine in New York. Dr van Delft’s research interests include understanding genetic influences underlying why teenagers have a poorer outcome than children when treated for ALL. Dr Cole has published extensively on the development of new diagnostic tests for brain toxicity and has identified a potential new drug target.
The team has the support of all of the UK’s main childhood cancer treatment centres, which will be recruiting patients to the study.
What difference will this project make?
This is an excellent proposal which may have high impact on prediction and potentially on future management of an important chemotherapy-associated side effect in paediatric ALL.
External reviewerAlthough most children diagnosed with acute lymphoblastic leukaemia (ALL) can now be successfully treated, in that they do not die from the disease, treatment-related toxicity remains a major problem.
Brain toxicity is a serious complication for which there is no current preventive treatment.
This work will determine whether it is possible to identify children at risk of brain complications from chemotherapy. If so, these children would then be candidates for new approaches to reduce the damaging effects of chemotherapy on the brain. This could involve ‘brain training’ programmes, new drugs and/or alterations in the chemotherapy regime.
One important outcome of the study is that it will determine whether a drug target recently identified by Dr Peter Cole in New York, might be relevant for young leukaemia patients. If so, this offers an exciting new drug target to treat or prevent brain toxicity without interfering with the anti-cancer effects of the chemotherapy.
Although this study concentrates on paediatric ALL, many other childhood cancers are treated with chemotherapy that can damage the brain. The results could, therefore, have relevance to a wide range of childhood cancers.
Read more: Treating childhood cancer | Side effects of treatment