Acute lymphatic leukemia (ALL) is the most common form of childhood cancer. In the Netherlands, about 110 children receive this diagnosis each year, of which between 15 and 20 are diagnosed with T-ALL. This is a variant in which T cells, a type of blood cell produced in the bone marrow, derail. Because of DNA-changes, those blood cells become leukemia cells. Thanks to intensive chemotherapy, four out of five children with T-ALL cure.
Every child with T-ALL is assigned to a risk group to determine the most appropriate treatment. The extent to which leukemia cells disappear after initial chemotherapy treatments is used for this end. Dr. Melanie Hagleitner, pediatric oncologist specialized in T-ALL at the Máxima Center: ‘Children in whom the T-cell leukemia does not respond well to the first chemotherapy are in the high-risk category. The chance of the leukemia cells returning in them is higher and the chance of cure is lower.' Therefore, research on T-ALL is mostly focused on this group of children.
Substantial increase in survival rate
Prof. Dr. Rob Pieters, pediatric oncologist specialized in leukemia and medical director of the Máxima Center, collaborated on an international study in which more than six thousand children with T-ALL participated worldwide between 2000 and 2018. 5% of this group of children had the high-risk variant. Pieters explains: ‘The survival of these children has increased significantly. Where previously 28% of the children were still alive ten years after diagnosis, it is now 55%. Despite the fact that the T-cell leukemia does not immediately respond well to chemotherapy, it appears that at least one out of two children survives.'
In the study published in Journal of Clinical Oncology, the researchers, led by the University of Milan, also looked at whether, in the high-risk variant, a stem cell transplant after multiple intensive chemotherapy treatments improved the chances of survival. They saw that two-thirds of children who received a stem cell transplant and in whom leukemia cells had disappeared after intensive chemotherapy survived their disease for 10 years or more, compared with half of those who received only intensive chemotherapy without a stem cell transplant. Pieters: ‘This has led to children with this very aggressive form of T-ALL now always receiving a stem cell transplant.’
New biological insights
In order to take next steps toward curing all children with T-ALL, researchers need a deeper understanding of the biological aspects of the disease. Therefore, under the leadership of research group leader Dr. Frank van Leeuwen, the international collaboration ATG4TAL, All together for T-ALL, has been established. 'We collaborate with the clinical ALLtogether study in which more than 200 children with T-ALL participate each year in 14 European countries. From all these children we collect clinical data and take leukemia cells at different stages of treatment. We characterize these extensively and store them. This forms the basis for looking for underlying biological mechanisms in children who do not respond well to chemotherapy. We hope to find new biological markers for these children to determine the intensity of the treatment in advance and also to find new targeted drugs.'
Within ATG4TAL, specialists from the clinic and laboratory from all over Europe are working together. The project is financially made possible by Fight Kids Cancer, a research program founded by organizations of parents and patient representatives active in pediatric cancer in Europe. The five funding organizations are: Imagine for Margo (France), KickCancer (Belgium), Fondatioun Kriibskrank Kanner (Luxembourg), CRIS (Spain) and Kika (Netherlands).