A lifesaving test which gives advance warning of leukaemia relapse in children is thecentrepiece of a major new trial which gets underway this month. Piloted for the last year in Bristol and several centres across the UK, the test ensures the accurate detection of minute numbers of leukaemia cells (minimal residual disease – or MRD) that remain after treatment but cannot be detected under the microscope.

“Until now the only way to monitor a child's response to treatment has been to look down a microscope for leukaemia cells in blood or bone marrow samples. This is an incredibly insensitive "steam age" method.  MRD monitoring is amazing new technique to measure a child’s response to leukaemia treatment,” says Dr Nick Goulden, one of the UK’s leading leukaemia experts from Bristol Royal Hospital for Children and the University of Bristol.

“After a decade of refining this ‘molecular microscope’ and a crucial year-long Leukaemia Research (LRF) pilot study we are now in a position to exploit the amazing potential of this test in treating acute lymphoblastic leukaemia,” he adds.

Forty years ago, less than 5% of 450 children diagnosed each year with leukaemia were cured, even after they had received several years of treatment. By the 1990’s this figure was approaching 75% due to the use of more intensive chemotherapy.

“But we have become frustrated with the lack of progress,” says Dr Goulden. “This disease still claims the lives of a hundred children each year, and critically, we also believe that up to three quarters of those who are cured may be overtreated.

“This test will enable us to select which patients are at high risk of relapse and which children could actually be cured with significantly less chemotherapy,” he adds.

Every child treated for leukaemia will have some residual leukaemia cells in their bone marrow after their first month of chemotherapy – known as induction treatment. This level may fluctuate between 1 in 20 cells to less than 1 in 10,000 cells. Until now, the problem has been that conventional techniques (the microscope) are not able to accurately measure the levels of these cells.

Over the next six years, each of the 2,000 children entered in the latest national childhood leukaemia trial (Medical Research Council ALL 2003) will be tested for minimal residual disease at the end of their induction treatment (day 28).

Samples of bone marrow will be sent to the to one of the four MRD centres across the country- Bristol, Glasgow, London, and Sheffield – for MRD monitoring. Depending on the level of disease the patients will be put into one of two treatment arms.

This MRD monitoring will be funded by Leukaemia Research (LRF), who today announce that they will be investing £1.2 million in this work.

Sir Walter Bodmer, chairman of the Leukaemia Research Medical and Scientific Advisory Panel says: "The tremendous knowledge we now have about our genes and the mutations which cause cancer is the foundation on which medical advances will be based.

“This is an exciting time for leukaemia medicine as the power of molecular biology allows doctors to treat children with leukaemia in a far more informed and controlled way whilst at the same time striving to reach that final goal of 100% survival"

When a child is diagnosed with leukaemia, their life is turned upside down overnight. Together with their family, their lives begin to revolve around the hospital for months and even years.

In addition to the physical side-effects of treatment, nausea, hair loss, stomach problems, there are many other problems which result from this treatment – resulting from time out of school, and lengthy periods away from friends. The impact of this should not be underestimated.

“For a child with low risk MRD, we will be able to reduce the amount of time they spend in hospital by up to 60%, says Dr Goulden. “This would represent a major improvement in quality of life – and a step closer our goal – cure with the minimum of disruption,” he adds.

Leading leukaemia scientists also believe MRD monitoring could have substantial cost savings for the NHS. “We believe a reduction in risk relapse could lead to substantially fewer bone marrow transplants – as many as 15 transplants a year – each costing up to £100,000 each, “ says Dr Goulden.

“Less chemotherapy for low-risk children will also reduce the cost of treatment dramatically,” he adds.