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Researching improvements in stem cell transplantation

Physicians and researchers work closely together at the Princess Máxima Center. Their goal: to apply new findings from research faster in the treatment room, for example for children undergoing a stem cell transplant. Dr. Marc Bierings: 'As a doctor I focus mainly on the outcome: healing .From a research perspective, on the contrary, the focus is also on treatment improvement and long-term effects.'
New blood cells are created from blood stem cells. These stem cells are found in the bone marrow, in the interior of the bones. For some children with acute leukemia (ALL or AML), a form of blood cancer, stem cell transplantation is the best suited treatment. These are children where chemotherapy does not work well enough. By introducing stem cells from a healthy donor into the bone marrow, new healthy blood cells are made.

Dr. Marc Bierings, pediatric oncologist and responsible for stem cell transplants in the Máxima: 'Every year, about 80 children in the Máxima receive a stem cell transplant. These are mainly children with cancer. Children with other diseases, such as metabolic diseases or blood production disorders, also receive stem cell transplants in the Máxima. The majority, about 50 children, receive donor cells. For the remaining children, we 'harvest' their own stem cells. These are stored frozen and returned via infusion after a high dose of chemotherapy. To be allowed to treat children as a stem cell transplant center, we have to follow strict rules and are licensed by the government.'

Biological mechanisms

Dr. Mirjam Belderbos is a pediatric oncologist and research group leader. Her goal is to unravel the mechanisms behind blood production: 'By better understanding exactly how blood is made by stem cells, we hope to discover new points of leverage for treatments for children undergoing stem cell transplants and for children with congenital disorders in blood production.'

Belderbos therefore analyzes the blood of children who underwent stem cell transplants. 'Using special techniques, I investigate the function of stem cells and their 'offspring'. These techniques make it possible to 'zoom in' very precisely, down to the level of a single cell. For example, we can see which stem cell is multiplying, or how a stem cell settles in the recipient's bone marrow. Eventually, we hope to learn how a small group of stem cells restores complete blood production. We can also look at the differences for each child and donor and investigate why a transplant works better in one child than another.'

Improved and personalized pretreatment

In preparation for a stem cell transplant, a child often receives chemotherapy. This suppresses the child's own bone marrow that is in the bones, making room for the new stem cells. Dr. Birgitta Versluijs, pediatric oncologist: 'Children with AML receive a so-called combination of three different chemotherapies at Máxima. This differs from those in many other European hospitals. Together we want to investigate in a study what the differences are in both the short and long term. Our goal is to harmonize use of the best pretreatment. This is not only best for the children, but this way we can also set up follow-up studies for a larger group of children.'

The study also focuses on the immune system of children who have had a stem cell transplant, but in whom the disease has returned. Dr. Mirjam Belderbos is also involved in this from the Máxima. Versluijs: 'It is very nice that we are also including the fundamental, biological aspects in this study. What we learn from this can then possibly lead to further improvement of stem cell transplantation as a treatment in the future. '

Previously, researchers from the Máxima and Wilhelmina Children's Hospital showed that individual dosing of the drug anti-thymocyte globulin (ATG) that, in addition to chemotherapy, prepares children for stem cell transplantation makes treatment safer. Dr. Rick Admiraal, one of the researchers involved and fellow in pediatric oncology, said, 'We compared children with a standard dose of ATG given in the past with children who received a personalized ATG dose. Then we saw a marked improvement in immune system recovery and, much more importantly, survival. Based on this study, every child who receives a stem cell transplant at the Máxima now receives a personalized dose of ATG.' 

Long term

As stem cell transplants continue to improve, the number of children who are cured is also growing, as is their life expectancy. Belderbos: 'Some children receive stem cells from an adult donor. As a result, these donor stem cells sometimes live longer than the normal human lifespan. To better understand how these stem cells adapt to their younger environment, I am therefore investigating long-term blood production in 'survivors' of childhood cancer. In this way, we hope to discover if, and which 'survivors' are at risk for age-related blood diseases. This knowledge can contribute to better aftercare for children after they undergo transplantation with older donor stem cells.'

Bierings: 'These studies are a sample of the many research projects that take place here every day. For example, Dr. Caroline Lindemans studies 'graft versus host disease,' a common complication after transplantation. Dr. Dorine Bresters is researching long-term cardiovascular side effects. It is very nice how, thanks to the establishment of the Máxima five years ago, all research and specialists in this field are coming together in one research hospital. Together we are thus making faster scientific progress that will further improve stem cell transplantation as a treatment for children.'