Matt Kaiser
Posted by
Matt Kaiser

Better, kinder treatments for children with blood cancer

Matt Kaiser
Posted by
Matt Kaiser
26 Sep 2014

When our charity started in 1960, fewer than one in every 10 children diagnosed with leukaemia lived more than five years. Now, for children with the most common form, nine in 10 survive. That's remarkable progress, and one we are very proud of our contribution to. That isn't the whole story though and we have a long way to go before our work on improving treatments for children with blood cancer is done. In this blog post, I outline the research that has allowed this transformation in outlook and the work that must be done to give children a life truly free of their blood cancer.

The birth of chemotherapy

At the beginning of the 1960s, most doctors considered acute leukaemia fatal. But inspired by the effects of war-time mustard gas on the white blood cells of soldiers, the idea of a new approach to treating cancer was born – chemotherapy. Most doctors at the time were sceptical this would ever work.

In the 40s and 50s, there had been some successes with the odd drug, but these were short-lived. But when doctors started combining different powerful chemotherapies, those early pioneers showed it was possible, for some at least, to start using the magic word – cure.

The practice of treating cancer with drugs was born and is now an integral part of beating many cancers.

The era of clinical trials

Over the next decades, successive clinical trials in the UK and overseas tested different combinations and different doses of drugs to figure out the best ones. Through shared learning and collaboration, a more complex schedule of various drugs at increasingly higher dosages became the standard.

The numbers of kids entering clinical trials rose, to over 90% in the UK. And the numbers surviving crept up too – by the 1980s, over 70% children diagnosed with the most common form of childhood leukaemia, acute lymphoblastic leukaemia (ALL), lived for five years or more. And by the 1990s, that figure was over 80%.

These chemotherapy drugs – some derived from the nitrogen mustard gas of warfare – work by interfering with normal cell growth and division. They can be good at hitting cancer because cancerous cells are often rapidly growing and dividing. The trouble is some healthy cells are too. So chemotherapies can have wide-ranging effects on the body's tissues by affecting other multiplying cells, like hair follicles, mouth lining and blood cells. This can lead to hair loss, nausea, mouth ulcers, tiredness, anaemia and low resistance to infection, amongst others.

The costs of intensifying treatment were more and more of these side effects and, in occasional tragic cases, death. But these negatives were outweighed by the growing number of kids who survived.

But if, in the past, some children survived without this intensified treatment, then it meant doctors were now in some cases giving unnecessarily excessive doses of drugs, with all the associated side effects. The problem was that they had no way of telling which groups of patients these were.

Personalising medicine

During the 80s and 90s, a genetic revolution was happening. Fuelled by technological innovation, our ability to visualise packets of DNA – chromosomes – in our cells and to read the DNA letters that make up our genes gave us a whole new level of understanding in cancer biology.

Our researchers and others round the world started to pick out the gamut of genetic alterations that underpinned childhood ALL, finding various genetic faults that predicted the aggressiveness of a person's disease.

Armed with this new knowledge, researchers in the mid-90s started to design clinical trials that split patients into different groups based on their genetic profile. Whereas previously we had a 'one-size-fits-all' approach, doctors started adjusting treatment to fit an individual's biology. Patients deemed 'low risk' received lower intensity treatment than patients with a higher risk.

And not long after, some of our researchers exploited ever-more sensitive molecular technologies to devise a test – called minimal residual disease (MRD) – that could accurately detect rogue leukaemia cells at a sensitivity of one in 10,000. This was incorporated into a clinical trial in 2003 and used to spot cancers that responded well to initial treatment. Doctors could ease off on the treatment, minimising side-effects while still delivering a cure. It could also detect at a very early stage when a cancer was threatening to come back, giving doctors reason to intervene with therapy.

The results were impressive – the UKALL 2003 trial delivered an increase in overall survival to over 90%, a reduction in relapses and significantly fewer treatment-related deaths. And it showed less chemotherapy was feasible in patients who had good early responses as revealed by MRD. It's success was extended to teenagers and young adults, eventually including patients up to 24 years old.

Far fewer patients required expensive stem cell transplants, and drug and nursing costs were lower. As a result, MRD testing in ALL was adopted as standard of care by the NHS.

Now and the future

Leukaemia & Lymphoma Research is now funding the next stage of work, the UKALL 2011 trial, to further refine MRD-based personalised treatments for children diagnosed with ALL.

But treatment still lasts at least two years and the harsh drugs in our treatment arsenal have remained largely unchanged since the birth of chemotherapy. Although now a minority, some children still die from their disease and most experience gruelling side effects from their treatment. And this during a time when kids are supposed to be growing, learning and having fun.

The problems don’t end there, either – we now know that the toxic effects on normal body cells can be long-lasting. Childhood leukaemia survivors are at greater risk of heart and lung problems, infertility, stroke, psychological and emotional issues, and even of developing new, second cancers later in life. A study last year estimated that by the time a childhood leukaemia survivor is 45 years old, they will have a 95% chance of developing a chronic health condition and an 80% chance of it being disabling or life-threatening.

This reinforces that it’s wise for childhood cancer survivors, even if they have been well for decades, to go for regular check-ups.

So our work isn’t done yet. We are further refining ways to dial down the intensity of treatment for certain groups of children without compromising survival chances. Recently, for instance, our scientists discovered additional genetic predictors that could allow doctors to de-intensify chemotherapy for more children with ALL. The UKALL 2011 trial is also systematically collecting quality of life assessments to ensure this is an end goal in itself.

And we’re thinking more radically too. Some of our scientists are going back to the lab with ever-more powerful genetic tools to uncover more of the biological faults driving childhood blood cancers. This is so we can develop next-generation therapies that precisely target the root of the cancer, similar to the approach pioneered in other blood cancers. This is like arming doctors with a scalpel rather than a baseball bat, and vastly reduces the toxic effects on healthy cells.

The community is also fostering the same sense of international collaboration that has got us where we are today. Because the number of children who relapse or become drug-resistant are becoming rarer, we need to run clinical trials for these patients in several countries to make sure we recruit sufficient numbers quickly enough. One trial run across Europe and Australia is already underway, and we’re funding an important complementary laboratory project to discover new predictors of treatment response and new biological targets to hit with drugs.

In the near future, our charity is set to use its experience in running a collaborative network of clinical trial centres in the UK – the Trials Acceleration Programme – to integrate trials testing potentially life-saving therapies in rare patient groups across Europe.

A hundred percent

And we need to do this for all childhood blood cancers. This article has focused on the most common – ALL – but we are equally dedicated to improving the lives of children diagnosed with any blood cancer. Powerful chemotherapy is the mainstay for treating acute myeloid leukaemia, and Hodgkin and non-Hodgkin lymphomas, so precision medicine is desperately needed for these too.

We strive for 100% survival and 100% quality of life. Children should be able to live the life they would have if they'd never had had a cancer, and we won’t stop until they do.



This is potentially a hugely significant breakthrough! Fingers crossed the trial gets the go ahead and is a huge success. Researchers rock!