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New research identifies relapse risk in a rare form of childhood leukaemia

The Bloodwise logo. Bloodwise appears in black text against a white background
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03 Aug 2016

Improving survival rates

The survival rate of children diagnosed with the most common form of childhood leukaemia – acute lymphoblastic leukaemia (cALL) – has steadily improved since the early 1960s. Certain types, however, such as childhood acute myeloid leukaemia (cAML), haven’t seen treatment advance to the same extent. Bloodwise-funded researchers in Newcastle are striving to address this problem and in a new study have revealed that an unusual genetic alteration can increase the risk of relapse in cAML.

Despite cALL being the most commonly diagnosed cancer in children, childhood leukaemia is still a rare condition. Approximately 350 new cALL patients and 60 new cAML patients are diagnosed per year in the UK. Thanks to decades of research, the 5-year survival rate of children with cALL now sits around the 90% mark, which had risen dramatically from less than 10% in 1960. The outlook for patients with rarer forms, however, is not quite as positive, with the average 5-year survival in cAML around 60%. This figure has been gradually increasing but an absolute priority for researchers studying childhood blood cancers is to emulate the progress of cALL and push towards 100% survival.

Laying the groundwork for future breakthroughs

One of the challenges of cAML research is that there are roughly six times fewer diagnoses than cALL, making it difficult to study. To tackle these issues, Bloodwise has funded a programme of research since 1993 to investigate the genetics of all childhood leukaemias. This research group collects samples from all children diagnosed with cALL or cAML in the UK and undertakes painstaking genetic analysis each and every time a sample is received.

The researchers also keep close track of each patient’s progress throughout their treatment. They then look back at the genetic data to identify which DNA changes affect the disease course and critically, which genetic alterations correspond to better responses to certain treatments. Over time, this information can be used to optimise treatment for patients, categorising them based on their genetic profile alongside other factors. This approach is known as treatment stratification, and has underpinned the successes in cALL treatment. Replicating it with cAML will hopefully reap similar benefits in the long-term.

A potentially important discovery

As the Newcastle group has been collecting samples for such a long time, they can now study even the rarest genetic changes in cAML. The new study published in the journal Leukemia looked at a genetic fault found in less than 1% of both adults and children with AML called 'trisomy 4'. The group used 87 clinical samples collected by themselves and other UK facilities between 1989 and 2009. Although the 'trisomy 4' genetic change did not appear to affect adults with AML, children with the specific alteration seemed to have a greater risk of relapse. These children did, however, respond well to the drugs used to overcome relapse, known as salvage therapy.

This is the first time 'trisomy 4' has been found to be important in predicting disease course in cAML. The researchers suggest that, in future, children that are found to possess the 'trisomy 4' fault should be monitored more intensely for signs of relapse so that doctors can intervene with salvage therapy if needed. If further clinical trials show this to add benefit, this could contribute to the ongoing push for better stratification for patients with cAML.

The importance of specialised research facilities

This potentially important finding was made possible due to the presence of specialised research facilities capable of the accurate storage, analysis and monitoring of large amounts of patient samples and information. These successes highlight why dedicated research centres are so important and will continue to play a critical role if we are to continue making progress in treating rare forms of childhood leukaemia.