Researchers have reported a range of genetic variations that may more accurately predict risk of relapse in children with standard-risk B-cell acute lymphoblastic leukaemia (ALL).
The findings may help identify the 15% of patients who experience relapse after remission, according to the US researchers.
Acute lymphoblastic leukaemia is the most common childhood cancer, with more than 90% of patients achieving remission. However, half of all relapses occur in patients designated as ‘standard-risk’. The researchers say this highlights the need to identify more specific markers of risk that can help doctors tailor treatment accordingly.
The research involved scientists from St Jude Children’s Research Hospital in Memphis, Seattle Children’s in Washington, and the Children’s Oncology Group, and was published in the Journal of Clinical Oncology.
The researchers studied 439 patients who relapsed and 1,057 who stayed in remission for five years. Most of the patients had been designated ‘standard-risk’ ALL (SR-ALL).
Subtypes of the disease with increased risk of relapse were PAX5-altered, TCF3/4::HLF, ETV6::RUNX1-like and BCR::ABL1-like. In contrast, hyperdiploid and ETV6::RUNX1 ALL had lower relapse risk, they report.
But crucially, the team identified other genetic changes within these B-ALL subtypes further influenced the risk of relapse.
Study co-leader Dr Mignon Loh, from Seattle Children’s, said: “We are planning to reduce conventional therapies in the future for children with ALL because we know that many patients can be cured with less therapy. We want to make sure we accurately identify those children, and because of the special design of the study, this project allowed us to do just that.
“Beyond conventional therapies, this information could also be used to develop and explore novel, personalised treatment strategies.”
Fellow study co-leader Dr Charles Mullighan, deputy director of the St Jude Comprehensive Cancer Center, said: “There remains a population of children whose disease is not fully cured, and we’ve not completely understood why that’s the case. This study focused on that group of poorly understood cases, where we know less about the features that influence the risk of treatment not working and the disease coming back.
“Children with SR-ALL should have their tumour cell genome sequenced upon their initial diagnosis to identify if their tumour cells have these high-risk features, so that their initial therapy intensity can be increased.”
Source:
Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. (2024) “Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia.” Journal of Clinical Oncology, 9 August 2024, doi: 10.1200/JCO.23.02238.
Link: https://ascopubs.org/doi/full/10.1200/JCO.23.02238
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