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Linde Dekker investigates fludarabine in CAR T therapy

The cure of children with acute leukemia receiving CAR T cell therapy could improve in the future if exposure to the drug fludarabine is optimized. Research results, on which PhD student Linde Dekker collaborated, already show this.

Linde Dekker's research in 6 questions and answers

1. How did you end up at the Máxima Center for your PhD research?

‘I was already familiar with the Máxima Center: during my Master I did a research internship in the group of Roland Kuiper; I liked that so much that I wanted to do my PhD in the Máxima Center. I am therefore very happy that this is possible here! I find the people in the Máxima Center very inspiring, and what I specifically like about my research is that I work a lot with doctors and the research can be directly translated to the clinic.'

2. Which children with cancer receive the therapy you are researching?

'Children with acute leukemia who have not responded to therapy or where the cancer recurrences after treatment, may receive hematopoietic cell transplantation and CAR T cell therapy. Fortunately, this is then still an option! In the case of hematopoietic cell transplantation, it involves all forms of acute leukemia, but for CAR T cell therapy only for children with acute leukemia in which the B cells are specifically affected. For both therapies, patients are in the Máxima Center a lot, but especially for hematopoietic cell transplantation.'

3. What is your PhD research about?

'I'm looking specifically at how we can improve these two therapies, hematopoietic cell transplantation and CAR T therapy; if we look at the immune cells before and after therapy, can we find the clue there already whether a patient is going to respond well? Or can we predict this from exposure to certain types of chemotherapy? And could we possibly adjust something in the therapy to improve the outcome of these patients?'

4. The name 'fludarabine' comes up quite often, why is that?

'With both therapies, patients are first given a combination of drugs to make room for the cells of the therapy. One of these drugs is fludarabine. Now we have seen in hematopoietic cell transplantation that if you give the same dose of fludarabine just before therapy, the actual exposure varies very much from patient to patient. This can depend on differences in body weight, body composition and the function of certain organs. Our study results show that exposure also varies greatly with CAR T cell therapy and this can predict clinical outcome, and it is therefore important to optimize the fludarabine dose so that each patient has the correct exposure.'

5. What did you find most striking about the study results?

'These results are promising, but they still need to be confirmed in a large clinical trial. This is now being worked on and will probably be an international collaboration. This will involve increasing the dose of fludarabine for CAR T therapy so that, based on our study, almost no patient is below the optimal exposure. That study should show whether the clinical outcome does indeed improve significantly. What struck me most was that we could already see such a large effect in a relatively small group of patients (in this case 26). And you could probably increase the chance of curing these patients with something as 'simple' as increasing the dose.'

6. What is it like to see an article published in an important journal?

'I am definitely happy with this publication! I hope to complete my entire PhD research in 2024. It is special to finally see the results of the research you worked so hard on for two years as a real publication. I also think the impact of this publication is very special: the results can be applied directly in the clinic and this will therefore happen, both in the Netherlands and abroad. If this research can ultimately lead to a higher chance of cure after CAR T therapy in the future, we are another small step closer to our center's goal!'