Some three percent of children with ALL have a DNA fault in their leukemia cells involving a gene from the so-called ABL class. Despite the fact that the Princess Máxima Center is the largest children's cancer center in Europe, this form of leukemia is diagnosed in only four children a year. Therefore, traditional clinical studies to test the effect of new drugs are very difficult to set up in practice.
Important basis for future research
The new study forms an important basis for future research into new treatment methods for children with this aggressive form of leukemia, because there is strong evidence that so-called tyrosine kinase blockers could work well as new targeted drugs against this DNA abnormality.
Researchers from the Princess Máxima Center, led by Monique den Boer and Rob Pieters, led the collaboration of 20 children's cancer centers worldwide. They looked at 122 patients with ALL whose leukemia cells contained the ABL class gene fault, to analyze the course of their disease. The children were treated between 2000 and 2018 and received chemotherapy with or without also undergoing a bone marrow transplant. At the time, tyrosine kinase blockers were not yet a first-line treatment option.
The analysis, published today in The Lancet Haematology, found that some 76 percent of children were still alive five years after diagnosis – a much worse outcome than in children with other forms of ALL, of whom more than 90 percent survives for five years or more. In 31 percent of children, the disease came back within five years of treatment, much more frequently than in the fewer than 8 percent of ALL patients without ABL gene fusions.
A new study is already underway to measure the effect of tyrosine kinase blockers in patients with this high-risk form of leukemia, and in the future the researchers hope their results will lead to a worldwide new treatment protocol for the disease.
Judith Boer, senior postdoc in the Den Boer group and co-author of the study, said:
‘In our new study, we’ve mapped out the disease course and DNA faults in a particularly aggressive form of ALL in great detail. Using this knowledge will help us determine whether new targeted tyrosine kinase blockers do indeed provide a better treatment for these patients.’