Personalising treatment for children with rare inherited conditions affecting their immune system

Inborn errors of immunity (IEI) are a group of nearly 500 rare inherited conditions that affect a child’s immune system, leaving them vulnerable to life-limiting complications.[1] A haematopoietic stem cell transplant (HCST) is the only potentially curative treatment, but it is a complicated procedure with inherent risks. Dr Tom Altmann of Newcastle University is developing a computer model that will allow doctors to predict the best dosing regimen for chemotherapy drugs used during HCST for each child, maximising the likelihood of successful transplantation with fewer side effects. He hopes this personalised approach will help to improve treatment outcomes and quality of life for children with IEI and their families.

How are children’s lives affected now?

Although inborn errors of immunity (IEI) are individually rare, collectively, these genetic conditions affect between one and five in 1,000 children.¹ The severity of these conditions can vary widely, ranging from mild to life-threatening illnesses.

“Having a defective immune system leaves these children susceptible to life-limiting complications – such as severe infections, autoimmunity, inflammation and cancer,” says Dr Altmann. “Without treatment, they may experience chronic illness that impacts their quality of life – and sadly, some may even lose their lives.”

Currently, HSCT– which involves replacing the child’s faulty immune cells with healthy ones from a donor – is the only potential cure. To create room for the donor cells, powerful drugs are used to destroy the child’s existing bone marrow, a procedure known as conditioning chemotherapy.

How could this research help?

“Our goal is to develop a new test that will enable doctors to provide individualised drug dosing regimens for HSCT conditioning,” says Dr Altmann.

Every patient’s body processes drugs differently, resulting in varying dosage requirements for each child undergoing conditioning chemotherapy. The ability to predict the appropriate doses of drugs to use is key – minimising the risk of side effects while ensuring the survival of the transplanted cells.

“We will first develop methods that can accurately determine the levels of three drugs used for HSCT conditioning chemotherapy,” says Dr Altmann. “We will then use these tests to measure the concentrations of these drugs in blood samples donated by children undergoing the procedure.”

Using this information, the researchers will develop a computer model that can be used to predict the right doses of these drugs needed for each child.

References

1. UpToDate? Inborn errors of immunity (primary immunodeficiencies): Classification. https://www.uptodate.com/contents/inborn-errors-of-immunity-primary-immunodeficiencies-classification [website accessed 25 April 2024]

*Research Training Fellowships

Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research.

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