Improving accuracy of diagnosis for childhood leukaemia
New cell analysis procedures have led to improved diagnostic techniques and national standards for cell processing.
Acute lymphoblastic leukaemia (ALL) is the most common form of leukaemia in children, affecting approximately one in 20,000 children. Research conducted over the last decade by Dr Allison Blair, Principal Clinical Scientist in Bristol’s School of Cellular and Molecular Medicine, has helped to improve diagnostic testing in children with ALL.
Improvements in therapy over the last ten years have increased survival rates to 80-85 per cent but the remaining 15-20 per cent of children with ALL suffer a relapse of the disease because not all the leukaemia cells are eradicated during treatment. Relapsed childhood ALL is the second most common cause of death in children in the UK.
Obtaining an accurate diagnosis is critical to improving the outcomes for relapsed children with ALL, however, indicators that the patient is at high-risk of relapse can be missed. Bone marrow samples are taken for analysis, but due to the unpleasant and invasive procedure involved, samples are usually of poor quality - particularly for infants.
If incorrectly diagnosed as low-risk, the patients may be put on a less intensive drug treatment plan, which fails to kill all the leukaemia cells, leading to a relapse.
Improving the quantity and quality of cell analysis
Dr Blair developed and described a procedure that enabled ALL cells to be grown over an 8-week period: the first description of these types of cells being grown in culture over a long term in an artificial environment.
Wessex Regional Genetics Laboratory implemented this new culture system in their diagnostic laboratory in 2005, and reported a 7.5-fold increase in the number of cells that could be tested as well as a 2-level increase in the quality of the cells: from poor to moderate. The system has further reduced the cost of analysis by one third.
The improvements have resulted in faster reporting times to clinicians and their patients, from nine days the year prior to implementation to seven days the year after, despite an increase in the number of samples being tested.
Setting national standards for cryopreservation cell processing
Dr Blair and her research group also investigated methods for freezing and subsequent thawing of paediatric ALL samples to determine whether it was possible to use frozen samples for research and clinical evaluation. They developed operating procedures for cryopreservation that allowed a 90 per cent recovery of the material upon thawing.
This pioneering work led to an invitation to join the steering committee of the Leukaemia and Lymphoma Research CellBank when it began in 2004. Dr Blair provided the scientific expertise for establishing standard procedures for processing and storing leukaemia samples. These procedures were implemented by all 6 UK centres that contribute samples to the CellBank and they remain the national standard for leukaemia cell processing.
The CellBank has been providing samples to approved research projects since 2007. As of 2013, more than 10,000 samples have been supplied to support 32 projects. Projects that have led to improved cancer drugs as well as improved understanding of leukaemia – the genetics, its distribution in the body and reducing side effects of drug therapy.
The cryopreservation techniques developed by Dr Blair and used to build the CellBank resource have been instrumental in enabling advancement of our understanding and treatment of leukaemia through high-quality research.