Scientists at the Wellcome Sanger Institute and the University of Cambridge found that in children with neuroblastoma – a cancer of immature nerve cells – platinum chemotherapy caused changes in the genome that could later cause leukemia in some children.
The findings published in the Journal Blood could lead to an ability to identify which children are more likely to develop secondary cancer. This, in turn, can lead to changes in their treatment plan to avoid these risks or take steps to prepare.
Secondary blood cancer is a challenging complication of childhood neuroblastoma cancer treatment. Every year, around 100 children in the UK are diagnosed with neuroblastoma*, and those who have undergone high-risk treatment are at increased risk of developing a secondary blood cancer – leukemia – after treatment with neuroblastoma.
Neuroblastoma often requires intensive treatment, including various chemotherapy drugs. These powerful drugs kill cancer cells very effectively, but unfortunately also have side effects, including damage to the DNA of healthy cells, including bone marrow cells. In up to 7 percent of childhood neuroblastoma survivors, damaged bone marrow cells develop into secondary leukemia.
In this new study, researchers from the Wellcome Sanger Institute and the University of Cambridge sequenced whole genomes of bone marrow and blood samples from two children who had both developed blood cancers after being treated with high-risk neuroblastoma. They found that the seeds of secondary leukemia were sown by neuroblastoma chemotherapy as early as 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 cause of secondary leukemia in these children, which appears to be in the early stages of neuroblastoma treatment. We hope.” further investigating this to try to identify children at higher risk and to inform a more tailored treatment plan to reduce the risk of secondary leukemia.”
The team found that in both patients the leukemia had mutations caused by neuroblastoma chemotherapy. A broader analysis of 17 children treated for various cancers then identified another child who had undergone neuroblastoma treatment and developed pre-leukemia seeds.
In the future, it may be possible to identify the children who are at higher risk of developing secondary leukemia by sequencing their genome and highlighting genetic drivers that may be precursors to blood cancers.
dr. Grace Collord, joint lead author of the Wellcome Sanger Institute, said: “This study would not have been possible without the contributions of the patients and their families, and we are deeply indebted to them for participating in this study. Understand the reason why some childhood cancer survivors develop secondary blood cancers is crucial if we are to find a way to help protect ourselves from 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 intensive chemotherapy treatment. Occasionally, this chemotherapy can cause serious side effects, such as leukemia. So these findings are important to possible strategies for monitoring secondary cancer and tailoring individual treatment plans. However, I must emphasize that it remains vital that children with high-risk neuroblastoma continue to receive intensive treatment for their cancer.”
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