Individual dosage of preparatory drug makes stem cell transplants safer for children

The individual dosage of a drug used to prepare children for stem cell transplantation makes this treatment safer. That’s according to new research from scientists at the Princess Máxima Center and Wilhelmina Children’s Hospital.

A stem cell transplant can be an important part of treatment for some children with leukemia. Preventing the immune system from rejecting new stem cells is key to the success of this treatment. For this purpose, children are pretreated with a drug called anti-thymocyte globulin (ATG). This drug weakens the immune system so that new blood stem cells can continue to make healthy blood cells.

In a new study published today in the leading journal The Lancet Hematology, researchers at the Princess Máxima Pediatric Oncology Center working with colleagues at Wilhelmina Children’s Hospital studied the effect of personalized ATG dosing. The research was funded by pharmaceutical company Sanofi, a maker of this drug, and ZonMw.

Dr. Caroline Lindemans is a pediatrician specializing in stem cell transplants at Princess Máxima Center and Wilhelmina Children’s Hospital in Utrecht, the Netherlands, and one of the study’s co-lead authors. She explains: “The more the immune system recovers after a transplant, the better a child’s chances of survival. We suspected that too high a dose and the wrong time to give a child ATG, one of the drugs that helps prepare for a stem cell transplant, could hamper the recovery of donor immune cells. In the past, the dose of ATG was determined based on body weight. In the new study, the number of immune cells before the stem cell transplant is also included in choosing the right dose for each child. The new dosing regimen was developed in collaboration with dr. Stefan Nierkens, group leader at the Princess Máxima Center.

Some 58 children who received stem cell transplants between 2015 and 2018 at the Wilhelmina Children’s Hospital or the Princess Máxima Center participated in the study. Dr. Rick Admiraal, one of the researchers on the team, compared the immune recovery and survival of these patients with that of children previously treated with the standard dose of ATG.

In 4 out of 5 children, the immune system fully recovered within 100 days of stem cell transplantation. A similar proportion survived for at least 3 years after stem cell transplantation.

This is a marked improvement over the results with the standard dose. There, we saw immune recovery and three-year survival in about two-thirds of the children.”

Dr. Rick Admiraal, Researcher, Princess Máxima Center

Lindemans: “As we had hoped, our results show that an individual dose of ATG leads to better immune recovery. The risk was that the donor stem cells would be rejected in more children, but luckily that was not the case. Our research therefore shows that this method of drug dosing makes stem cell transplants safer.


Journal reference:

Admiral, R. et al. (2022) Individualized dosing of anti-thymocyte globulin in pediatric allogeneic hematopoietic stem cell transplantation (PARACHUTE): a single-arm phase 2 clinical trial. The Lancet Hematology.

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