New cancer cell screening is improving childhood leukaemia treatment

November 14, 2017, Newcastle University
New cancer cell screening is improving childhood leukaemia treatment
Credit: Newcastle University

A study has shown that current methods used to determine the correct level of chemotherapy required for each young patient may be improved by looking at the genetic make-up of the child's cancer cells.

Findings have already led to changes to tailoring for newly diagnosed children, with around half of youngsters with good risk genetics being spared intensive treatment.

The results may also be used to identify those children at the highest risk of relapse who would benefit most from new types of treatment, such as CAR-T cell therapy.

The research, by scientists at Newcastle University and doctors at Great Ormond Street Hospital and the Bristol Royal Hospital for Children, was funded by the blood cancer research charity Bloodwise and Children with Cancer UK.

The study is published online today in the Journal of Clinical Oncology.

Targeted treatment

Methods currently used to guide intensity of treatment for each child relies heavily on a test – known as minimal residual disease (MRD) - that measures levels of cells remaining in the blood after the first month of chemotherapy.

MRD gives a clear indication of how quickly a patient is responding to treatment. Children are placed into 'low risk' or 'high risk' treatment regimes, based on whether the number of leukaemia cells detected by their MRD test is above or below a single threshold.

A team led by Professor Anthony Moorman, from the Northern Institute for Cancer Research, Newcastle University, analysed leukaemia cells from more than 2,500 children whose treatment had been guided by the MRD test between 2003 and 2011.

The research has shown that combining the results of MRD analysis with genetic profiling doctors will be able to significantly improve the accuracy of predicting relapse of the disease and improving treatment options.

Anthony Moorman, a Professor of Genetic Epidemiology, who co-leads the Leukaemia Research Cytogenetics Group at Newcastle University, said: "Risk stratification is a key component of improving survival rates and reducing side-effects for children with leukaemia.

"This study indicates that using a traditional MRD threshold to assign patients to different treatment groups should be refined with the integration of detailed genetic testing, to more accurately identify children with a lower or higher risk of relapse.

"Taking into account key genetic abnormalities that influence outcome will ensure that MRD thresholds for more or less intensive chemotherapy are more flexible and each child gets the most appropriate treatment.

"The idea of combining or integrating MRD and genetic information to refine the allocation of patients to different risk groups has been fully adopted in the next clinical trial, which is currently being designed and will hopefully begin in late 2018."

Diagnosis rates

More than eight in 10 children diagnosed with the most common form of childhood cancer, acute lymphoblastic leukaemia (ALL), will now survive.

Treatment remains highly toxic and can have severe short and long-term side effects. The outlook is much poorer for children whose disease relapses, with fewer than six in 10 surviving longer than five years.

The researchers divided children into groups depending on whether their leukaemia cells contained genetic abnormalities known to be associated with a 'good', 'intermediate' or 'high risk' of relapse.

While children's genetic risk of relapse broadly corresponded with their MRD test – assigned risk category, this was not always the case.

The study found that children who had a 'good risk' genetic profile but whose blood was made up of between 0.01 and 0.1% leukaemia cells - just above the MRD threshold - actually had excellent chances of survival whether they were given standard treatment or intensive treatment.

As a result of the findings, the MRD threshold at which children who are cytogenetic 'good risk' are treated with the most intensive treatment has now been raised, reducing treatment toxicity for around 50 children a year in the UK, without compromising their chances of survival.

Improving outcomes

Dr Alasdair Rankin, Director of Research at Bloodwise, said: "Current treatments for children with leukaemia are highly toxic and can have devastating side-effects both in the short and the long term. New ways to reduce treatment intensity, without reducing chances of survival, are desperately needed.

"This study represents another advance in personalising care and should mean that more children get the right treatment for them."

Dr David O'Connor, Consultant Paediatrician in Haematology at Great Ormond Street Hospital, said: "Through this new research we have been able to take an important step forward to identify, earlier on, leukaemia patients who require more targeted therapy.

"This study suggests that early detection of patients' specific treatment needs can improve patient outcomes, and reduce the risk of relapse and complications for those patients identified. This study represents an exciting advance in personalised medicine."

The study also identified a group of children currently treated with low intensity chemotherapy as a result of their low MRD test results who also have high risk genetics and who experience high rates of relapse. Indeed, nearly all children in the high risk genetics group who did not have a negative MRD result a month after treatment had very high relapse rates and may respond better to new types of treatment.

By examining children's MRD test results on a sliding scale, instead of whether they were simply above or below a certain threshold, the large-scale study demonstrated that children with very high levels of MRD treated with intensive treatment were much more likely to relapse than who were just above the threshold.

Cliff O'Gorman, chief executive of Children with Cancer UK, said: "By developing a new method of measuring MRD, we can significantly improve the accuracy of predicting how likely it is that a child with leukaemia will relapse. This has made more personalised treatment a possibility for young patients since we launched the trial in 2003, and helped to drive five-year survival for childhood above 80%.

"But there is still much more to do. Children and young people diagnosed with cancer face aggressive treatments that can have a long-term impact on their health and well-being. It is crucial that we build on this breakthrough and continue to fund further studies and clinical trials to develop kinder, more effective treatment for young cancer patients in the UK."

Explore further: Breakthrough in cancer cell screening advances personalised treatment of childhood leukaemia

More information: David O'Connor et al. Genotype-Specific Minimal Residual Disease Interpretation Improves Stratification in Pediatric Acute Lymphoblastic Leukemia, Journal of Clinical Oncology (2017). DOI: 10.1200/JCO.2017.74.0449

Related Stories

Breakthrough in cancer cell screening advances personalised treatment of childhood leukaemia

August 18, 2016
Researchers at Newcastle University have been able to accurately predict how children whose cancer returns after treatment for leukaemia are likely to respond to further treatment.

New antibody drug conjugate could be used to target treatment-resistant childhood leukaemia

May 18, 2017
Researchers at The University of Manchester have discovered that a protein (5T4) found on the surface of cells contributes to chemotherapy resistance in the most common type of childhood leukaemia. Using a novel approach, ...

Rare leukaemia survival-rate breakthrough

August 13, 2013
A pioneering genetic study means that children with a rare subtype of leukaemia have 75% less chance of their leukaemia recurring.

We made great strides with childhood leukaemia – we can do the same for brain cancer

November 9, 2017
Brain cancers are the leading disease-related cause of death in Australian children. And survival rates have changed little in decades. As a paediatric oncologist, the worst conversation I can have with my patients or their ...

Scientists identify genetic drivers of leukaemia

August 2, 2012
(Medical Xpress) -- Scientists at Newcastle University have discovered three key genetic errors which can dictate how adult patients develop leukaemia and respond to treatment and could help doctors adapt future treatments.

Simple test could improve treatment for biggest leukaemia killer

January 21, 2016
A simple blood test capable of detecting trace levels of leukaemia cells remaining after intensive chemotherapy has been developed by scientists at the National Institute for Health Research (NIHR) Biomedical Research Centre ...

Recommended for you

In zebrafish, a way to find new cancer therapies, targeting tumor modulators

September 21, 2018
The lab of Leonard Zon, MD, at Boston Children's Hospital has long been interested in making blood stem cells in quantity for therapeutic purposes. Looking for a way to test for their presence in zebrafish, their go-to research ...

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

Cancer immunotherapy might benefit from previously overlooked immune players

September 20, 2018
Cancer immunotherapy—efforts to boost a patient's own immune system, allowing it to better fight cancer cells on its own—has shown great promise for some previously intractable cancers. Yet immunotherapy doesn't work ...

New way to target advanced breast cancers

September 20, 2018
A cytokine signature found in certain kinds of breast cancer cells can not only serve as a diagnostic tool for HER2-negative cancers but also offer an effective treatment target.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.