10:35am Thursday 24 August 2017

Leap in survival rates for childhood leukaemia patients with rare genetic abnormality

A study by Newcastle University scientists, published online on Monday in the Journal of Clinical Oncology, has shown that lives have already been saved as a result of identifying children carrying a chromosomal abnormality known as iAMP21 and giving these patients a very intensive treatment regimen.
 
Overall survival for acute lymphoblastic leukaemia (ALL) patients, a cancer of the white blood cells, is now very high, with up to 90% of children being cured. A minority of patients, however, still do not respond to standard treatment.

A decade ago, the same scientists, funded by the blood cancer charity Leukaemia & Lymphoma Research, discovered the genetic error known as iAMP21. This abnormality occurs when parts of chromosome 21 – one of 23 pairs of chromosomes that contain our genetic instructions – are copied and shuffled around, resulting in extra copies of some genes. The researchers found that this abnormality was present in around 2% of children diagnosed with ALL and that it gave them a much greater chance of suffering a relapse.

The team, led by Professor Christine Harrison and Professor Anthony Moorman from the Leukaemia Research Cytogenetics Group, tracked the progress of patients with iAMP21 using samples from clinical trials between 1997 and 2002. They found that more than 80% of patients with iAMP21 had relapsed, compared to less than for 25% for children overall. The long-term survival for the iAMP21 group was also much lower.

Since 2003, bone marrow samples from every child diagnosed with ALL have been tested for the presence of iAMP21 using a genetic test known as ‘fluorescence in situ hybridisation’ (FISH), which binds glowing tags to DNA and “lights-up” the abnormal sequences. Children with iAMP21 registered on the UKALL2003 trial, which was funded by Leukaemia & Lymphoma Research and the Medical Research Council, were immediately recommended for treatment using a very intensive protocol.

The results of the UKALL2003 trial show that if children with iAMP21 are treated with intensive chemotherapy they have a dramatically reduced risk of relapse. In addition the proportion surviving for five years or more increased to nearly 90%.

Anthony Moorman, Professor of Genetic Epidemiology at Newcastle University, said: “Although using the presence of genetic abnormalities to guide treatment is not new within childhood leukaemia, such a clear demonstration of its beneficial impact on survival is extremely rare. In time we may be able to design drugs to actually target the iAMP21 abnormality, sparing these children from toxic treatment.” 

Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “By establishing how different genetic abnormalities found in leukaemia cells dictate how well the child will respond to treatment, we can identify high-risk patients early on. These new results demonstrate the huge potential of personalised medicine.”
 
ENDS

For further information, please contact Henry Winter at Leukaemia & Lymphoma Research Press Office on 020 7269 9019, 07824 375880 or email: hwinter@beatingbloodcancers.org.uk

NOTES TO EDITORS

The report is published online in the Journal of Clinical Oncology under the title, ‘Risk directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukaemia and intrachromosomal amplification of chromosome 21: A comparison of MRC ALL97/99 and UKALL2003 trials’. Principal authors: Prof Anthony V Moorman, Professor Ajay Vora and Prof Christine J Harrison, Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, UK  

The Leukaemia Research Cytogenetics Group (LRCG) at Newcastle University has been funded by Leukaemia & Lymphoma Research for over 20 years. The LRCG maintains the largest cytogenetic database of its kind in the world; containing genetic data from more than 27,000 children and adults diagnosed with acute leukaemia and treated on UK and international clinical trials

About Leukaemia & Lymphoma Research
Leukaemia & Lymphoma Research is the only UK charity dedicated to improving the lives of patients with all types of blood cancer, including leukaemia, lymphoma and myeloma. Its life-saving research is focused on finding causes, improving diagnosis and treatments, and running ground-breaking clinical trials for all blood cancer patients. Around 30,000 people of all ages, from children to adults, are diagnosed with blood cancers such as leukaemia, lymphoma and myeloma every year in the UK.

NEWCASTLE UNIVERSITY is a leading UK higher education institution with a reputation for international excellence built on the quality of teaching, research and work with the community and industry. The University is a member of the Russell Group of 20 leading UK universities that are committed to maintaining the very best research, an outstanding teaching and learning experience and unrivalled links with business and the public sector. The University is based in the city of Newcastle upon Tyne, in North East England. 


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