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 at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.
The test can predict which patients with acute myeloid leukaemia (AML) are at risk of their cancer returning in the future, helping to guide doctors on what further treatment is needed.
A similar test revolutionised treatment for the most common form of childhood leukaemia when it was introduced nearly a decade ago. It is used to separate children into high and low intensity treatment groups depending on how they respond to the first stages of chemotherapy. This is the first time that this type of test has been used for the most common adult form of acute leukaemia.
In research published online in the New England Journal of Medicine, scientists used a ‘minimal residual disease’ (MRD) test to predict relapse, using blood samples from 346 AML patients who had undergone two cycles of chemotherapy. The patients all had AML driven by faults in the NPM1 gene, which the new test can identify. NPM1 mutated AML is the most common genetic sub-type of the disease and accounts for a third of all cases.
AML is a type of blood cancer diagnosed in around 2,400 people each year in the UK and survival rates are extremely poor, with fewer than two in 10 patients surviving for more than five years. The leukaemia can be cured in patients who are able to tolerate intensive treatment and outlook is better in these patients.
The best chance of a cure involves intensive chemotherapy, but it is very common for AML to come back or ‘relapse’. When doctors think that a patient is at high risk of their leukaemia returning, they can often be treated with a stem cell transplant. Finding a donor can take time and the treatment itself is very hard for patients, so knowing exactly who is likely to need a transplant is important.
The researchers found that MRD testing was far superior at predicting relapse compared to current methods, which mainly rely on analysis of genetic abnormalities within individual patients’ cancer cells that influence whether they are ‘high risk’ or ‘low risk’ at the start of treatment.
The MRD test can determine if a patient is in ‘molecular remission’, which means there are no signs of the faulty genes indicative of leukaemia cells in their blood. In 82% of cases in which the MRD test detected the presence of the NPM1 cancer gene in a blood sample taken after initial treatment, the patient had relapsed within three years. Just 30% of patients who had no detectable leukaemia cells in their blood at this stage went on to relapse within that time.
Molecular relapse occurs long before any physical or clinical signs of relapse are apparent. The MRD test could help doctors to monitor patients after treatment and take pre-emptive action before full-scale relapse occurs. This can be measured to a sensitivity of one leukaemia cell in 100,000 healthy blood cells. Sequential testing over time can identify nearly all patients who will relapse before any clinical signs appear.
The research was funded by the blood cancer charity Bloodwise and the National Institute for Health Research (NIHR) and embedded in the Cancer Research UK-funded National Cancer Research Institute (NCRI) AML17 trial, sponsored and run by from Cardiff University under Chief Investigators Professor Alan Burnett and Professor Nigel Russell, Nottingham University Hospital. The trial treated patients from across the UK, Denmark and New Zealand. All samples analysed using MRD testing were from patients determined to be at ‘standard risk’ of relapse using existing testing.
Professor David Grimwade, Principal Investigator at the NIHR BRC at Guy’s and St Thomas’ and King’s College London who led the research, said: “Conventional methods for guiding treatment for this aggressive type of leukaemia are inadequate. The MRD test is an invaluable tool to assess treatment response and identify those patients for whom chemotherapy is not sufficient and require stem cell transplantation or new treatments.”
Alasdair Rankin, Director of Research at Bloodwise, said: “Research to improve the treatment for acute myeloid leukaemia is really important as current treatment is very demanding and survival rates are not good enough. Identifying people who can benefit from a stem cell transplant accurately and as early as possible would give them the best chance of success and could also protect some people who don’t need a transplant from unnecessary treatment.”
Life Sciences Minister George Freeman MP said: “This ground-breaking study has the potential to have a major impact on the treatment for patients suffering this devastating condition. It is studies such as this which highlight the importance of the government’s commitment to health research and collaboration with research charities. These exciting developments are being made possible thanks to our investment of more than £1 billion a year through the National Institute for Health Research.”
Dr Robert Hills, who coordinated the clinical trial and collected data for the project from the Haematology Clinical Trials Unit, based in Cardiff, said: “The data we’ve collected from patients has given us a new insight into Acute Myeloid Leukaemia (AML). Looking at the disease while people are receiving treatment has given us a unique opportunity to learn much more about how best to treat. What we have been able to identify is a group of patients who otherwise would be thought to do quite well, who in fact have a very poor prognosis, and who are not well served currently. This opens up the exciting prospect that we can do the same for other groups of patient as well.”
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Notes to Editors
The findings will be published online in the New England Journal of Medicine on 20 January 2016under the title ‘Assessment of Minimal Residual Disease in Standard-Risk AML’. Corresponding author: Professor David Grimwade, Department of Medical and Molecular Genetics, King’s College London
Bloodwise is the UK’s biggest blood cancer charity dedicated to improving the lives of patients. The charity, which was formed in 1960, changed its name from Leukaemia & Lymphoma Research in September 2015. The charity’s research is targeted at understanding more about blood cancer, finding causes, improving diagnosis and treatments, and running groundbreaking clinical trials for patients. The charity champions patients’ needs by influencing relevant decision makers and influencers, and seeking to raise awareness of the issues faced by patients. Their patient services provide information, support and assistance to patients at every stage of their journey.
Around 38,000 people of all ages, from children to adults, are diagnosed with blood cancers and related disorders every year in the UK. It is a complex disease area made up of 137 individual diseases. Some affect thousands of people, such as common forms of leukaemia, lymphoma and myeloma. Others affect only a handful. But together, blood cancers are the fifth most common form of cancer. For more information visit www.bloodwise.org.uk.
The National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust is run in partnership with King’s College London. As one of the first five (of 11) biomedical research centres in England we were funded by the National Institute of Health Research to help establish the UK’s translational biomedical research infrastructure. With embedded world class research platforms, a range of hosted research organisations and partnerships with industry, this represents the foundation for London’s premier biomedical cluster. We are arranged around four research clusters. For more information visit https://www.guysandstthomasbrc.nihr.ac.uk/
About King’s College London
King’s College London is one of the top 20 universities in the world (2015/16 QS World University Rankings) and among the oldest in England. King’s has more than 26,500 students (of whom nearly 10,400 are graduate students) from some 150 countries worldwide, and nearly 6,900 staff. The university is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
For more information, please visit King’s in Brief (www.kcl.ac.uk/newsevents/About-Kings.aspx).
Guy’s and St Thomas’ NHS foundation Trust provides more than 2 million patient contacts in acute and specialist hospital services and community services every year. As one of the biggest NHS trusts in the UK, with an annual turnover of more than £1.3 billion, we employ around 13,650 staff.www.guysandstthomas.nhs.uk
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (www.nihr.ac.uk)
The BRC’s exist within the context of King’s Health Partners, an Academic Health Sciences Centre (AHSC) which is a pioneering collaboration between King’s College London, Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts. For more information, visit http://www.kingshealthpartners.org
About Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
- Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated.
- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
- Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that 3 in 4 people will survive their cancer for at least 10 years within the next 20 years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK’s vision is to bring forward the day when all cancers are cured.
Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research intensive universities. The 2014 Research Excellence Framework ranked the University 5th in the UK for research excellence. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, University Chancellor Professor Sir Martin Evans. Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise encompasses: the College of Arts, Humanities and Social Sciences; the College of Biomedical and Life Sciences; and the College of Physical Sciences and Engineering, along with a longstanding commitment to lifelong learning. Cardiff’s flagship Research Institutes are offering radical new approaches to pressing global problems.www.cardiff.ac.uk