July 30, 2020

The survival rate of children with acute lymphatic leukemia (ALL) has increased to 90% in recent years. According to Dr. Inge van der Sluis, pediatric oncologist at the Princess Máxima Center, it can only improve through international cooperation: ‘As we aim for 100% survival, we are part of a major international study into ALL in children, called ALLTogether1. Last week we were the second center in Europe to start.’ The goal: to further improve the treatment and chances of survival of children with ALL and to reduce side effects.

The ALLTogether1 protocol concerns the treatment of children with acute lymphatic leukemia. The study is expected to last five years and will be carried out at (pediatric) oncology centers in as many as 14 European countries. Approximately 1,400 children per year will participate in the study, more than 110 of whom Dutch. Pediatric oncologists / researchers in a large part of Europe now follow the same treatment protocol. In this protocol, randomized studies are conducted to compare different treatments.

International cooperation
Until now, subsequent ALL protocols were simply given a number as their name. Since 2014 a new international consortium has collaborated in the field of ALL, and for this reason Rob Pieters, pediatric oncologist and member of the Princess Máxima Center’s Board of Directors, came up with a different name: All Together. The Netherlands has made an important contribution and coordinates various sub-studies from the Princess Máxima Center. Based on extensive analyses of the latest treatment results of all participating countries and on other studies worldwide, the ALLTogether1 protocol was developed step by step. Inge van der Sluis, principal investigator on behalf of the Máxima, says, ‘This requires a lot of time and openness from all experts in the field of leukemia in children.’

Inge van der Sluis: ‘What our children actually notice from this study? They receive the best treatment possible at the moment, based on the knowledge and experience from many countries. The treatment is becoming more and more tailor-made, adapted to the individual patient. For example, children are divided into different risk groups based on genetic abnormalities in leukemia cells and how well they respond to the start of therapy. Then, for children who have a very high chance of recovery, we look into whether we can make the therapy less intensive and hence reduce the side effects. For other children, we look into whether the chance of recovery will increase by adding new forms of immunotherapy and new chemotherapy agents to the two-year treatment. One patient will need more therapy, whereas another will be able to recover with less therapy.’

Research questions
In addition to the changes in therapy, many other studies are taking place in the background, for example to improve diagnostics, prevention and treatment of side effects, and more basic laboratory research into the underlying DNA abnormalities of leukemia cells. By joining forces, the important research questions will be answered more quickly. Everything for the ultimate goal: the best treatment for a higher survival rate with good quality of life for children with ALL.

Examples in the study
For children with a low risk of relapse, we look into whether chemotherapy agents that can damage the heart in the long term can be reduced. For children with a high risk of relapse on the other hand, the treatment is actually intensified, using new forms of immunotherapy in which antibodies against leukemia cells and the child’s own immune cells are used against leukemia. For some children medicines are added that target certain proteins or leukemia cell abnormalities. These medicines have recently been examined in relapsing leukemia patients, but we now want to use them upon first diagnosis in order to be able to cure more children sooner. In addition to the new medicines, the usual medicines are better monitored by, for example, measuring their blood levels.

Inge van der Sluis, pediatric oncologist and principal investigator, says, ‘We are proud of this special and large-scale collaboration and of the ALL treatment protocol itself! We expect to be able to contribute a great deal to the study on the basis of our expertise in the coming period, with pediatric oncologists, researchers, (research) nurses, as well as staff of the laboratories and the Trial and Data Center.’

Josef Vormoor, pediatric hematologist and clinical director, says, ‘I’m used to communicating final results, but this is good news. The opening of this important study on July 7 is definitely a major milestone! It is a unique collaboration with a great many countries to improve the treatment of ALL in children.’

Rob Pieters, pediatric oncologist, chair of the ALL Group (and member of the Board of Directors), says, ‘Over the last few years, we have collaborated intensively with a number of other countries to develop the new treatment. Now it is there: ALLTogether1. I am proud that, not only as the eponym of this study but also as one of the founders, we can now start this treatment and research. Working with so many international institutes in the field of ALL… there’s only one fitting name for that!’

Source: Prinses Máxima Centrum voor kinderoncologie