25 July 2023

The results of a Dutch study of a new treatment protocol for children with acute lymphoblastic leukaemia have shown a large improvement in five-year survival, particularly for a poor-prognosis group.

Dr Rob Pieters of the Princess Maxima Centre for Paediatric Oncology, Utrecht, the Netherlands led a team who measured the effectiveness of their new ‘ALL11’ protocol.

The study recruited 819 child and adolescent patients treated between April 2012 and July 2020. Patients were put into three groups: standard risk, medium risk, and high risk. 

Overall, five-year survival was 94%, with event-free survival at 89%. Results of the study were published in the Journal of Clinical Oncology, and presented previously at the ASH annual meeting in December 2022.

In the ALL11 protocol, patients with IKZF1 deletions (also known as ‘Ikaros leukaemia’) who fitted into the medium risk group received an extra year of maintenance therapy. In a ‘landmark analysis’ at two years after diagnosis, the prolonged maintenance therapy resulted in a 3-fold lower risk of the cancer returning within five years. The cumulative risk of relapse with ALL11 was 26%, compared to 9% with the previous ALL10 protocol with only two years of maintenance therapy for this group.

The ALL11 protocol also reduced anthracycline chemotherapy for three groups of patients, with susceptibility to side-effects or extremely good survival rates – which included children with Down’s syndrome and ETV6-RUNX1 mutated cancer. This resulted in fewer adverse events with similar survival rates to the previous ALL10 protocol.

Dr Pieters said: “The five-year survival rate for children with acute lymphatic leukaemia has increased dramatically since the 1960s, from zero to 94%, but the last steps are the most difficult.

“There is broad interest worldwide in this research, because it was still unknown how to improve therapy for children with Ikaros leukaemia.’

He added: “We are now one step closer to curing all children with acute lymphatic leukaemia. We have also been able to remove a drug that gives risk of heart damage largely from the treatment of children with less aggressive disease.

“So, the latest results for children with leukaemia fit exactly with our mission: more cure, with fewer side effects.”

Source:

Pieters R, de Groot-Kruseman H, Fiocco M, Verwer F, Van Overveld M, Sonneveld E, van der Velden V, Beverloo HB, Bierings M, Dors N, de Haas V, Hoogerbrugge P, Van der Sluis I, Tissing W, Veening M, Boer J, Den Boer M. (2023) “Improved outcome for acute lymphoblastic leukemia by prolonging therapy for IKZF1 deletion and decreasing therapy for other risk groups.” Journal of Clinical Oncology, doi: 10.1200/JCO.22.02705

Link: https://ascopubs.org/doi/full/10.1200/JCO.22.02705  

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