Researchers from Newcastle University and Great Ormond Street Hospital have identified new predictors of relapse in children and young people with acute lymphoblastic leukaemia (ALL) treated with the immunotherapy drug blinatumomab, as part of UK-wide study.

Their findings challenge long-standing assumptions based on traditional chemotherapy treatments and could help doctors tailor treatment more precisely to individual patients.

Shaping UK treatment guidelines

Published in Blood Advances, the study is the first comprehensive analysis of relapse risk factors in children receiving blinatumomab as a replacement for parts of standard chemotherapy.

The findings suggest a more targeted approach could spare some children unnecessary chemotherapy while maintaining excellent outcomes and have already led to revisions of national UK treatment guidelines.

Professor Anthony Moorman, joint lead author from Newcastle University, said: "Blinatumomab is transforming the treatment of childhood acute lymphoblastic leukaemia, but until now we did not know whether the risk factors used for decades in chemotherapy-based treatment still applied.

"Our findings show that many of them do not. Instead, a child's early response to blinatumomab, together with specific genetic features of their leukaemia, provides a much more accurate picture of relapse risk.

"This research will help clinicians identify which patients are likely to do exceptionally well with reduced chemotherapy and which will require a different treatment approach.

“Reducing exposure to chemotherapy has the potential to lessen side effects and improve quality of life, while ensuring that higher-risk patients receive the treatment they need."

Dr Sujith Samarasinghe, Consultant Paediatric Haematologist at GOSH and joint lead author, said: "Being able to accurately predict how this kinder, more effective medicine will help our patients means less chemotherapy, more days at school, more time at home and ultimately more time spent being children. 

"We are already seeing the real-world impact of this work, with the findings now helping guide how children across the UK are treated."

The national study involved more than 200 young patients with B-cell acute lymphoblastic leukaemia treated across 24 centres in the UK and Ireland.

Treatment response data were collected through regional laboratories and genetic testing, including whole genome sequencing, was performed through NHS Genomics Laboratory Hubs before being analysed centrally.

The study found many of the risk factors traditionally used to predict relapse in childhood acute lymphoblastic leukaemia, including age, white blood cell count, high-risk genetic features and measurable residual disease before blinatumomab treatment, were no longer reliable indicators for patients receiving this immunotherapy-based approach.

Instead, the strongest predictor of future relapse was the amount of leukaemia remaining after the first cycle of blinatumomab.

The team also identified two genetic subtypes, known as IKZF1plus and DUX4-rearranged leukaemia, which were associated with a poorer response to treatment and a higher risk of relapse.

The power of early response

Using these findings, the researchers developed a new risk-stratification tool called BlinPredict, which combines early treatment response with genetic information to identify patients most at risk of their cancer returning.

Researchers say the findings mark an important step towards a new generation of treatment strategies designed specifically for the immunotherapy era.

The research was supported by Horizon Europe, Marie Slodowska-Curie Action and Cancer Research UK.

Future work will focus on understanding why some leukaemias are resistant to blinatumomab and on identifying risk factors in other patient groups, including adults with ALL.

Reference: Early response and genetics define relapse risk after frontline blinatumomab in childhood B-ALL: A cohort study. Miguel Vieira Martins et al.  Blood Advances. DOI: 10.1182/bloodadvances.2026021026