New insights into the treatment of childhood leukaemia

New study about acute lymphoblastic leukaemia

On the surface, the statistics about acute lymphoblastic leukaemia (ALL) are encouraging. Thanks to decades of painstaking research and clinical advances, around eight in 10 children and young adults with the disease are cured.

But for the families of those children who are the ‘two in 10’, this impressive statistic is cold comfort.

That’s why many scientists around the world – including our own – are working hard to ensure even more children are successfully treated.

Today we spotted a huge global study that represents an important step in the fight against ALL. It points to better ways to treat the small number of children who don’t respond to their initial treatment.

We spoke to Cancer Research UK scientist Professor Josef Vormoor about the research, and asked him what he thought of its implications.

Phases of chemo

ALL is a cancer of white blood cells called lymphocytes (also known as B-cells and T cells), which are important for defending the body against disease. ALL arises when the bone marrow starts producing too many immature lymphocytes (called lymphoblasts), which can’t function properly. The aim of treatment is to kill off these lymphoblasts.

There are usually three main phases of chemotherapy: induction, consolidation and maintenance. The goal of induction therapy, which lasts 4 to 6 weeks, is to push the leukaemia back and bring the disease into remission. This happens when blood tests no longer show abnormally high levels of lymphoblasts.

Rather than billions of cells at the beginning of treatment, induction chemo brings the numbers down to millions. The second and third phases of chemo, which together last for up to three years, are intended to eradicate the remaining lymphoblasts.

The latest study looked at the two to three per cent of children for whom induction therapy fails to bring about remission, and the characteristics of their disease that might give a clue to why they don’t respond to treatment.

International collaboration

The main difficulty of trying to work out why induction treatment fails, says Professor Vormoor, is that even the most common childhood cancers are rare in the general population. “ALL is not that common a disease, and it’s even rarer for early chemo to fail,” he told us.

In the UK, for instance, Prof Vormoor estimates there are only around eight to 10 children each year who have ALL that fails to respond to induction therapy.

This means it’s hard to get enough patients together in one hospital or area to do any meaningful research.

“The beauty of this new study is that it’s a huge international collaboration, which involves 14 studies across three continents,” he said. “Researchers were able to pull together data on over 44,000 ALL patients over 15 years. And – crucially – this included over 1,000 children whose cancer didn’t go into remission after induction therapy.”

The study is in fact the largest ever of such ALL cases, and is the first to publish comprehensive information on the characteristics of children who do not respond to induction therapy.

Main findings

Professor Vormoor explained that the main finding of the study is surprising. Overall, only around 30 per cent of the children who did not respond to initial chemotherapy survived long term. But this quite dismal figure masked major variation in survival, depending on the biological characteristics of the cancer, and the type of additional treatment the children received after induction therapy:

• A subgroup of children with ‘B-cell’ type ALL had a much better survival – over 50 per cent survived long term
• These children were aged 1 to 5 years old or had more than 50 chromosomes in their leukaemia cells, rather than the normal set of 46 (known as hyperdiploidy)
• Together, around one-quarter of children who didn’t go into remission following induction therapy were in this better survival group
• The younger children with ‘B-cell’ type ALL did even better if they were treated with chemotherapy alone – over 70 per cent survived long term
• By contrast, children with ‘T-cell’ type of ALL seemed to have a better outcome if they were given a bone marrow transplant rather than chemotherapy

These findings are important. Usually children who don’t respond to induction therapy are thought to be at very high risk of a bad outcome and so are given a bone marrow transplant as standard.

According to Professor Vormoor, such transplants have traditionally been seen as the “final option” to cure the leukaemia. Actually, he says, these new results suggest that there is a group of “slower chemo responders” who benefit greatly from additional chemotherapy and who may not need a transplant.

And equally, other patients are much better off receiving a bone marrow transplant.

What next?

Professor Vormoor says this new study is an example of how we’re “continuing steady progress against ALL” and finding ways to drive the cure rate up even higher. In the immediate term, this research could result in children who don’t respond to initial chemo being given follow up treatment that is better personalised to their disease.

He’s very optimistic for the future, but cautions that much more needs to be done to ensure the two in 10 patients who aren’t cured of their disease at the moment are given the very best chance of survival:

“What science and medicine have achieved for children with ALL over the past 30 years is undoubtedly tremendous. But challenges remain – we urgently need to do more for children who aren’t cured.”

He also said that we “must never lose sight of the children we’re treating”. It’s not good enough just to drive up cure rates; we also need to make gentler treatments with fewer long-term side effects.

He hopes that research on childhood ALL as pursued by many groups worldwide will lead to such treatments. This includes his own work on cancer stem cells.

Steady march

Newspaper headlines often trumpet ‘breakthroughs’, ‘magic bullets’ and ‘wonder drugs’, but actually much of cancer research is about learning how better to use the treatments we already have, and finding out which patients will benefit from the different types that are available.

Along with meticulous studies to understand the inner workings of cancer cells, this type of work is the bread and butter of cancer research.

And this study is another example of many across the globe that contribute to the steady march towards improved survival for cancer patients.

Reference

Schrappe, M. et al. (2012). Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia New England Journal of Medicine, 366 (15), 1371-1381 DOI: 10.1056/NEJMoa1110169

Further information

To support Cancer Research UK’s ongoing work into beating children’s cancer, you can ‘Give Up Clothes for Good’ – it’s the UK’s biggest and longest running charity clothing collection that turns your unwanted clothes into cash to help more kids beat cancer. Fill any bag with quality clothing and drop it off at a TK Maxx store during April.

Your clothes could save lives. Each bag could raise £30 to help fund research into children’s cancers. The partnership has already raised £10 million to help beat children’s cancer and hopes to raise £2.5 million from this campaign to support groundbreaking work.