'Extending chemo slashes risk of aggressive childhood leukaemia'

UTRECHT [Netherlands]: Many kids with ALL experience a successful course of the disease. Nine out of 10 kids are cured after two years of chemotherapy.

However, the condition can be more severe in some kids. For instance, children whose leukaemia cells carry the so-called Ikaros alteration in their DNA are more likely to experience relapse after therapy.

The treatment regimen has been regularly modified throughout the years on the basis of the most recent scientific findings in order to increase the chances of survival and quality of life for all children with leukaemia.

The results of the ALL-11 treatment protocol were presented at the annual meeting of the American Society of Hematology this Saturday by prof. dr. Rob Pieters, medical director and paediatric oncologist at the Princess Maxima Center for paediatric oncology in the Netherlands (ASH).

The Dutch researchers examined the advantages of a customised course of treatment in several leukaemia patient populations, including kids with the Ikaros anomaly. In the Netherlands, this approach was used to treat more than 800 kids between April 2012 and July 2020.

Threefold lower risk of recurrence: Children with Ikaros leukaemia received an extra year of chemotherapy in the 'maintenance phase' on top of the first two years of treatment. This change lowered the risk of their cancer coming back by threefold: this happened in only 9 per cent of them, compared to 26 per cent of the children in the previous treatment protocol.

87 per cent of children with Ikaros leukaemia survived their disease for five years without their cancer coming back, an improvement of the 72 per cent in the previous protocol. Because of the extra year of chemotherapy, this group of children had a slightly higher risk of infection, but these were treatable. The extended therapy did not lead to any additional side effects.

Analysis of data from all children with ALL, regardless of subtype, showed that the five-year survival rate has improved stepwise over the past 30 years from 80 per cent to 94 per cent under the ALL-11 protocol. Safe reduction of treatment In the ALL-11 protocol, doctors and researchers also looked at the benefit of a less intensive treatment plan for three groups of children.

This included children with a DNA change in their leukaemia cells linked to a very high chance of recovery and children with Down syndrome who experience more severe side effects.

These children received treatment without or with a lower dose of anthracyclines, a type of leukaemia drug that increases the risk of heart damage and infections. The reduced treatment proved successful: children had the same or even a better chance of survival, while their quality of life improved due to a lower risk of infections and damage to the heart.

Globally, there is much interest in Dutch research as it has been unclear how to improve therapy for children with Ikaros leukaemia. The results have now been presented for the first time at the largest blood cancer conference and could lead to changes in treatment protocols for these children worldwide.

Prof. dr. Monique den Boer, medical biologist and group leader at the Princess Maxima Center for pediatric oncology, played an important role in the adapted therapy for children with the Ikaros gene change. She says, "The Ikaros mutation was first discovered about 15 years ago in children with leukaemia who had a poor prognosis, partly thanks to the emergence of new DNA technologies.

We saw that cancer came back in many of these children shortly after the end of the two-year treatment plan. I am very proud that our lab findings have now found their way into the clinic and can make such a big difference for children with leukaemia." Prof. dr. Rob Pieters, a pediatric oncologist and medical director of the Princess Maxima Center for pediatric oncology, led the clinical study and presented the results at the American Society of Hematology Annual Meeting.

He says, "the five-year survival rate for children with acute lymphoblastic leukaemia has increased enormously since the 1960s, from zero to 94 per cent, but the last steps are the most difficult." "We are now one step closer to curing all children with ALL.

We have also largely been able to remove a drug that poses a risk of heart damage from the treatment of children with a less aggressive form of the disease.

The latest results for children with leukaemia, therefore, fit in perfectly with our mission: curing more children with cancer, with fewer side effects."