Childhood Leukaemia and the Central Nervous System

Cancer is the leading cause of death for children aged 1-14 years and despite improvements in survival, leukaemia still accounts for about a quarter of these deaths. Even if cured, many survivors have significant chemotherapy side-effects resulting in late mortality, reduced academic achievement, poor quality of life and accompanying health and societal impacts.

The commonest long-term effects are adverse neurological/neurocognitive outcomes seen in 20-40% of patients with acute lymphoblastic leukaemia (ALL) 1,2.This reflects the use of neurotoxic agents to prevent ALL relapse within the central nervous system (CNS). There is an urgent need to develop more effective, and less-toxic, treatments for CNS-ALL. This is the key mission of our childhood leukaemia research group.

Our current therapies for CNS-ALL are both toxic and onerous. Treatment involves up to 26 chemotherapy injections into the CSF via spinal-tap under sedation/anaesthetic. Current tests to detect leukaemia in CSF are crude, so treatment is given to all children and young adults, without knowing how much is really needed.

Short-term side-effects include fits (affecting about 1-in-10 patients). Longer-term side-effects include reductions in intelligence, attention span and memory (affecting about 1-in-3 patients). There are likely to be many children that are overtreated and some that require more intensive treatment but currently we have no reliable way to find this out.

Another problem is that we haven’t had any new drugs for CNS-ALL for the last 60 years. This is exacerbated by the inability to measure CNS-AL accurately – so it is difficult to work out if a new drug is working without waiting a long time to see if the leukaemia comes back.

Research aims

Our research aims to address the two major barriers to progress in the field:

  1. an incomplete understanding of the key biological mechanisms underlying ALL survival in the CNS microenvironment.
  2. a lack of clinically useful CNS-ALL diagnostic and prognostic biomarkers. 

As well as this we are interested in finding out why only some children get neurotoxicity and if there are any ways we can prevent or reduce the side-effects of our current treatments for CNS leukaemia.

Research themes

We have three research themes:

For a full list of publications from our lab, visit Professor Chris Halsey's research profile.