Frequency and prognostic value of unconventional genetic subtypes in paediatric and young adult B-cell precursor acute lymphoblastic leukaemia in Taiwan

Unconventional genetic subtypes of B-cell precursor acute lymphoblastic leukaemia (B-ALL) were analysed to compare their frequency and their impact on outcomes between children and young adults in Taiwan. Unconventional subtypes were found in 23.0% of 456 paediatric B-ALL and 24.5% of 139 young adult B-ALL. The most frequently unconventional subtype both in children and young adults was BCR::ABL1-like, which could be subdivided into different kinase-altering aberrations in 67.3% of children and 78.6% of young adults. CRLF2-R was more frequent in children, while IL7R mutations were more common in young adults. In children, favourable outcomes were observed in patients with DUX4-R and PAX5alt, whereas those with BCR::ABL1-like and MEF2D-R had inferior outcomes. BCR::ABL1-like and MEF2D-R were also the independent predictors of inferior event-free survival in children. Conversely, most unconventional subtypes in young adults were associated with adverse outcomes except for DUX4-R. We found a lower incidence of BCR::ABL1-like and a better prognosis for paediatric PAX5alt in Taiwan compared to the West. Additionally, genetic differences were identified between paediatric and young adult BCR::ABL1-like subtypes. The extremely poor prognosis for unclassified young adults highlights the potential use of further subdivision of unfavourable genetic subtypes in refining risk classification and treatment optimization.