Stem cell transplants are used to treat children with certain cancers and other serious diseases. ATG is a drug used in these transplants to prevent the new immune system from attacking the body, a complication known as graft-versus-host disease (GvHD). However, standard doses of ATG can lead to delayed recovery of the immune system, increasing the risk of infection.
PARACHUTE Study
In the PARACHUTE study, researchers investigated model-based dosing of ATG, where the dose is precisely calculated for each child. Rick Admiraal, fellow pediatric oncology and researcher, explains: ‘We have developed a model that allows us to determine the optimal dose of ATG for each child. This results in faster immune recovery and fewer post-transplant complications.’
Improved survival and fewer complications
The study followed children for five years and compared the results of personalized dosing with the conventional approach in which each child receives the same dose. Children who received personalized dosing had an 18% higher survival rate. They also had fewer complications, such as serious infections and GvHD.
Caroline Lindemans, pediatric oncologist specialized in stem cell transplants, emphasizes the importance of these results: ‘By tailoring the dosage of ATG to the individual needs of each child, we can significantly improve the outcomes of stem cell transplantation.’
International recognition
The personalized dosing method is now being used in several centers around the world. Stefan Nierkens, leader of the research group, adds: ‘Our approach has been included as standard of care in several international studies, both in Europe and the United States. This underlines the value of our findings for the international community. This development offers hope for children undergoing stem cell transplantation by increasing the prospect of improved survival and quality of life.’
Research method: Accurate dosing through mathematical models
To test the efficacy of model-based dosing of ATG, researchers analyzed data from 214 children who underwent stem cell transplantation. These included 58 children from the original PARACHUTE trial and 156 additional children who were subsequently treated with the same method at the Princess Máxima Center and Memorial Sloan Kettering Cancer Center in New York. The results of this group were compared with 100 children who had previously received a standard dose of ATG.
Model-based dosing used mathematical models to calculate the optimal amount of ATG for each child. This was based on body weight, immune cells and other patient-specific factors. The primary endpoint of the study was the overall survival of the children. In addition, the researchers looked at secondary endpoints such as immune system recovery, prevention of GvHD and number of serious infections.