High-risk leukemia is more aggressive in children with Down syndrome

Children with Down syndrome have a lower chance of survival from a particular high-risk form of leukemia (ALL) than children without the disability, new research shows. Researcher Naomi Michels in the Den Boer group: ‘We need to continue the search for targeted therapies and immunotherapy for these children.’

Children with Down syndrome have a higher risk of developing acute lymphoblastic leukemia (ALL) than children without this disability. Around five of the 125 children a year with a new diagnosis of ALL in the Princess Máxima Center have Down syndrome.

Children at higher risk of their cancer coming back usually receive more intensive treatment. But that’s not possible for children with Down, as they tend to have more side effects from treatment. The syndrome is a genetic disorder – but the possible effect of DNA changes in leukemia cells in Down was still unknown.

In a new study, scientists from the Princess Máxima Center and the Erasmus Medical Center compared the effect of therapy in leukemia patients with and without Down syndrome. The international study, involving researchers from the United Kingdom, Germany, Scandinavia and Australia, was published today (Tuesday) in Lancet Haematology. In the Netherlands, the study was funded by the Princess Máxima Center Foundation and the Children's Oncological Center Rotterdam Foundation.

Treatment equally effective

To account for differences in known risk factors, data from 136 leukemia patients with Down syndrome were matched with those from 407 children who did not have Down syndrome. The matched ‘duos’ had the same age, ALL subtype, and blood results ​​at diagnosis. That’s how the researchers knew that any differences that remained were linked to Down syndrome.

Their analysis showed that the levels of leukemia cells decreased equally well in both groups of children after the first month of treatment. But the scientists discovered an important difference in longer-term outcome between children with and without Down syndrome in the so-called Ikaros form of ALL.

Increased chance of cancer coming back

A DNA error in the Ikaros gene leads to a more aggressive form of the disease in all children with leukemia. But children who also had Down syndrome had an even worse outcome than children without the disability, the researchers found.

Naomi Michels, PhD student in the Den Boer group, also part of the Oncode Institute, was involved in the study. ‘The Ikaros gene mainly increases the risk of cancer coming back,’ she says. ‘Children with Down syndrome and Ikaros ALL were more likely to see their leukemia return within five years of treatment.’ This was the case in 37 per cent of these children, compared with 13 per cent of Ikaros ALL patients who did not have Down syndrome. In other types of ALL, there was no notable difference between children with and without Down syndrome.

Fewer side effects

The researchers believe the difference has to do with an interaction between the genetic changes in Down syndrome and the Ikaros gene. Michels: ‘We need to continue the search for treatments with fewer side effects – such as targeted therapies and forms of immunotherapy – in order to be able to better treat children with Down syndrome who have this high-risk form of ALL.’

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Note to editors

This analysis concerns data from the Dutch Cancer Registry, administered by IKNL, on all patients in the Netherlands aged 0-17 years who were diagnosed with cancer between 1990-2015. This includes all malignant tumors, and one benign type of brain tumor. The stage of disease classification follows the International Classification of Childhood Cancer.

For more information about this research and/or about the Princess Máxima Center for pediatric oncology:

Sarah Wells, research communications advisor,

E: s.wells@prinsesmaximacentrum.nl T: +31 (0)6 50 00 66 07

About the Princess Máxima Center

Every year some 600 children in the Netherlands are diagnosed with cancer. One in four children with cancer still dies from the disease.

In order to cure children from cancer, all care and research in the Netherlands is concentrated in the Princess Máxima Center for pediatric oncology in Utrecht. More than ten years ago, parents and healthcare professionals took the initiative. The new pediatric oncology center was opened by Queen Máxima of the Netherlands on 5 June 2018.

The mission of the Princess Máxima Center is to cure every child with cancer, with optimal quality of life. The Princess Máxima Center is the largest pediatric oncology center in Europe where care and research are closely intertwined. Approximately 400 scientists and more than 800 healthcare professionals work closely together.