British researchers are closing in on being able to identify which children treated for neuroblastoma are at increased risk of developing secondary leukaemia, it has been announced.
"The seeds of secondary leukaemia are sown by neuroblastoma chemotherapy right at the beginning of treatment," say Dr Sam Behjati of the Wellcome Sanger Institute, Cambridge, and colleagues.
Therapy-related leukaemias are one of the most challenging complications of cancer treatment, particularly in children, where they make up the majority of non-relapse related cancer deaths. However, the origins of these leukaemias is unclear.
The researchers explain that small studies in adults suggest a role for clonal haematopoiesis, the overrepresentation of blood cells derived from a single clone. This is seen in about 4% of children after cytotoxic chemotherapy treatment, but is “vanishingly rare” in the general population.
They tested DNA in blood and bone marrow samples donated by two children at various stages of their treatment for neuroblastoma, who went on to develop therapy-related blood cancers. With whole genome sequencing, they identified early clonal haematopoiesis linked to mutations caused by platinum chemotherapies used in induction therapy. In a cohort of 17 other children with cancer, they identified another child who had undergone neuroblastoma treatment and had developed similar clonal haematopoiesis linked to platinum chemotherapy.
Identifying the ‘seeds’ of secondary leukaemia early in the treatment of these children raises the possibility of in the future being able to determine which children are at higher risk and altering their treatment plan.
Dr Behjati 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.”
Co-author Prof John Anderson added: “Neuroblastoma can be an aggressive disease that requires intense chemotherapy treatment. Occasionally this chemotherapy can cause serious adverse effects such as leukaemia. However, I should stress that it remains vital that children with high risk neuroblastoma continue to receive intense treatment for their cancer.”
Coorens THH, Collord G, Lu W, Mitchell E, Ijaz J, Roberts T, Oliver TRW, Burke GAA, Gattens M, Dickens E, Nangalia J, Tischkowitz M, Anderson J, Shlien A, Godfrey AL, Murray MJ, Behjati S. (2021) “Clonal hematopoiesis and therapy-related myeloid neoplasms following neuroblastoma treatment.” Blood, doi: 10.1182/blood.2020010150
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