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Secondary leukaemia risk for children treated for neuroblastoma studied by Sanger Institute and University of Cambridge scientists

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Some children with neuroblastoma who are given platinum chemotherapy may be at risk of later developing leukaemia because it cause genome changes, scientists at the Wellcome Sanger Institute and University of Cambridge have found.

It is hoped the findings could help identify those more likely to develop the secondary cancer, enabling their treatment plan to be changed or measures to prepare for the risk.

Sam Behjati, of the Wellcome Sanger Institute
Sam Behjati, of the Wellcome Sanger Institute

Every year, about 100 children in the UK are diagnosed with neuroblastoma, a cancer of immature nerve cells.

It often requires intense treatment, including several powerful chemotherapy drugs, which kill cancer cells very effectively but have side effects, including damaging the DNA of healthy cells such as bone marrow cells.

In up to seven per cent of childhood neuroblastoma survivors, damaged bone marrow cells go on to develop secondary leukaemia.

Sequenced the whole genomes of bone marrow and blood samples of two children who both had developed blood cancer following high-risk neuroblastoma treatment, the scientists found the seeds of secondary leukaemia were sown by the chemotherapy right at the beginning of treatment.

Dr Sam Behjati, co-lead author and group leader at the Wellcome Sanger Institute, said: “We have been able to unravel the root of secondary leukaemia in these children which seems to lie in the early stages of neuroblastoma treatment. We hope to further investigate this to try to identify children at higher risk, and to inform a more tailored treatment plan to reduce the risk of secondary leukaemia.”

A wider analysis of 17 children treated for various cancers identified another child who had undergone neuroblastoma treatment and developed pre-leukaemia seeds.

It is hoped that sequencing the genomes of such patients could in future highlighting any genetic drivers that could be pre-cursors for blood cancer.

Dr Grace Collord, joint first author from the Wellcome Sanger Institute, said: “This research would not have been possible without the contributions of the patients and their families, and we are indebted to them for their participation in this study.

“Understanding the reason why some childhood cancer survivors go on to develop secondary blood cancer is crucial if we are to find a way to help protect against this devastating complication.”

Professor John Anderson of Great Ormond Street Hospital, who contributed to this study, said: “Neuroblastoma can be an aggressive disease that requires intense chemotherapy treatment. Occasionally this chemotherapy can cause serious adverse effects such as leukaemia. So these findings are important to inform possible strategies for monitoring for secondary cancer and tailoring individual treatment plans. However, I should stress that it remains vital that children with high risk neuroblastoma continue to receive intense treatment for their cancer.”

The research was published in the journal Blood last Thursday.

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