The Road to Beating Childhood Leukaemia

I first started looking after children with blood disorders, including those with childhood leukaemia, in 1979. I was a senior house officer in paediatrics at the Royal Hospital for Sick Children in Glasgow. Back then, survival rates for childhood acute lymphoblastic leukaemia (ALL) were way below 50% but now, survival approaches 90%. It’s quoted as one of the big success stories in leukaemia, but also in cancer more generally.

We’ve made a lot of progress over the years and have discovered key ideas in research that have really driven this progress forward.

An individual drug might have a temporary, powerful effect but you need to combine treatment if you want to make sure children don’t see their disease return. We also realised over the years that we have to use stronger treatment and continue treatment for much longer than we originally believed. Previously, after treatment we’d use a microscope to see if there were cancer cells left in the blood or bone marrow after treatment and it looked like there were no cancer cells left. But in fact, the microscopes we used just weren’t powerful enough to let us see them. It’s these remaining cells that cause the disease to return. The strength and duration of treatment we were previously using weren't enough to destroy these lurking cells, and we now have far more sophisticated ways of identifying treatment-resistant cells– this makes us much better able to make decisions about what further treatment the child needs.

We discovered that there are parts of the body, which we call “sanctuary sites”, where leukaemia cells manage to survive and are not very easily targeted by standard forms of chemotherapy. The two main sanctuary sites in ALL are the central nervous system and testicles for boys. Treatments had to be designed that were able to target these sites without too much toxicity, as really toxic treatment would cause profound and life-altering affects. We now use combinations of chemotherapy to target these sites to stop the leukaemia returning.

One of the main problems in the early days of leukaemia treatment was its toxicity and sadly some children would die during their treatment from infection, bleeding or due to the effects of chemotherapy. We’ve completely changed how we manage these things nowadays – we give children platelets to try and stop potential bleeding and we give them antibiotics and antifungals to try and prevent infections.

Because of the number of children who get leukaemia and because of the way the paediatricians, haematologists and oncologists work together, clinical trials in childhood ALL were trailblazers. This meant that the effects of different treatment combinations could be rigorously tested against each other which in turn allowed new and better treatments to be selected. These trials have been happening since the 70s and have really helped to improve outcomes.

New technology has also helped us to improve things. We now have the ability to accurately measure very low levels of residual leukaemia, so we no longer rely on looking for leukaemia cells down a microscope. Technology now means that if there is one cancer cell in a sample of 1,000,000 cells, we can usually detect it, which means we don’t stop treatment unless we’re confident the cancer has gone, and this has helped to prevent relapse in children. It means if children need more intensive treatment to get rid of these lurking cancer cells we can give it to them, and it means if children don’t, we spare them from the toxic side effects.

It sounds fantastic, 90% survival nowadays compared to less than 50%, but of course there’s still that 10% where lives are lost, and those children are just as important as the ones who were cured. And many children are left with long term side effects from treatment. So, the disease is in no way beaten and as we get better at treating ALL, the rate of progress slows for that final 10% and it’s harder to discover new things that will have an impact on how we treat the disease.

Technology has the potential to advance things even further. We want to be able to create a genetic fingerprint of a child’s leukaemia that would tell us the specific changes driving a child’s leukaemia, the treatment it is most likely to respond to, and to help identify any treatments that a child might react badly to. This is important, as we see great variability in how children respond to treatment. It applies to all aspects of health really – for example, some children regularly pick up bad colds, while others have much milder symptoms. This is all based on the genes you inherit, and we want to be able to understand how this will influence a child’s response to cancer treatment to make sure we don’t give them any treatment they are likely to react badly to.

I think that progress for the remaining 10% of children with leukaemia who relapse is likely to be incremental. There are many reasons why people don’t respond to treatment, and we need to understand more about the causes of leukaemia and the mechanisms by which cells manage to avoid treatment. This will ultimately help us work out how to target the cells that resist treatment. These are the things that are key to curing the final 10%. We’ll probably need new drugs to be able to do this and the process is likely to be a lengthy one, but it’s needed if we’re going to cure that final 10%.

There’s also an intriguing possibility of being able to prevent childhood leukaemia. We know that some children are born with a genetic mark that puts them at higher risk of developing the disease, but only around one in 100 of these children will go on to develop it because a second or third additional change needs to happen for leukaemia to develop. We’re actually doing a trial at the moment looking at umbilical cord blood in children who have gone on to develop leukaemia. We want to look at whether changes that drive leukaemia were present at birth and what cells they were present in. We think that although many children have a change at birth that might increase their likelihood of developing leukaemia at birth, this is only really relevant if the change exists in a certain cell.

We don’t yet know enough about this and so I think it's far too early to start screening all children at birth for their leukaemia risk. But if we could pinpoint which children have a relevant genetic change, we might be able to treat children at the highest risk of developing the disease with chemotherapy that is much milder and that way prevent leukaemia developing.

I don’t think it’s possible to completely eradicate leukaemia, as there are just some things we cannot control. But I do believe we can get to a place where it’s not as serious, and no longer a death sentence. I would like to think that in another 30 years’ time we’ll be curing 95% of childhood ALL cases.

But this relies on several things, including a high quality, properly funded NHS that allows teams time to collaborate with one another. We also need to make the setup of clinical trials easier. It’s extremely complex at the moment, and I think unnecessarily so. We also need to make sure we don’t see childhood leukaemia as a “done deal”. As I say, every child in that last 10% matters as much as the children in the first 90%, and we need to make sure we keep funding research into the disease to improve things for that last 10%.