AML 17

blood cells

Cardiff University scientists in the Centre for Trials Research are part of a UK team to develop a simple blood test capable of detecting levels of leukaemia cells remaining after intensive chemotherapy.

Background

Working alongside experts from King’s College London, a team led by Professor Robert Hills from the Haematology Clinical Trials Unit based in the Centre for Trials Research, provided crucial data from current patients with leukaemia.

The test helps 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.

Professor Robert Hills, who coordinated the clinical trial and collected data for the project, 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 patients as well.”

Minimal residual disease (MRD) testing better predicts relapse

AML is diagnosed in around 2,400 people each year in the UK. Although survival rates are extremely poor overall, outlook for younger patients able to tolerate intensive treatment is better, with over half of patients under 40 years old surviving for at least five years.

Looking at the disease while people are receiving treatment has given us a unique opportunity to learn much more about how best to treat.

Dr Robert Hills, Haematology Clinical Trials Unit, Cardiff University

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 is the most common genetic sub-type of the disease and accounts for a third of all cases.

The best chance of a cure involves chemotherapy and, in the case of high-risk patients, a stem cell transplant. While intensive treatment is normally successful in sending the cancer into remission, relapse is very common.

Patients usually only undergo a stem cell transplant after chemotherapy if they are adjudged to be at high-risk of relapse and are fit enough.

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.

International trial

The study was conducted within the National Cancer Research Institute (NCRI) AML17 clinical trial, which 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.

Molecular remission

The MRD test can determine if a patient is in ‘molecular remission’, which means there are no signs of the faulty molecules indicative of leukaemia cells in their blood. This can be measured to a sensitivity of one leukaemia cell in 10,000 healthy blood cells.

In 82% of cases in which the MRD test detected the presence of the NPM1 cancer gene in a blood sample after 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.

Research impact

Alasdair Rankin, Director of Research at Bloodwise, who funded the research, said:

“Treatment for acute myeloid leukaemia is highly toxic and survival rates are desperately poor, particularly for older patients.

“Preemptive treatment to prevent relapse in those most at risk would reduce the levels of toxic treatment needed and improve its chances of success.”

The findings were published online in the New England Journal of Medicine under the title ‘Assessment of Minimal Residual Disease in Standard-Risk AML’.

Funders: Bloodwise and the National Institute for Health Research (NIHR)

Chief Investigator: Professor Alan Burnett