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Caroline Lindemans: ‘Quality of stem cell transplants is getting better and better’

Every year the Princess Máxima Center evaluates the results in the treatment of children undergoing a stem cell transplant. These are discussed with fellow teams from the adult department at the UMC Utrecht and the Leiden pediatric SCT team. Pediatric immunologist Caroline Lindemans carried out the so-called outcome analyses at the Máxima. ‘We’re getting better at preventing serious complications.’
A stem cell transplant (SCT) is one of the cellular therapies in (pediatric) oncology. Since the opening of the Máxima there has been intensive collaboration on stem cell transplants with the Wilhelmina Children’s Hospital, the UMC Utrecht and the LUMC in Leiden. There is a division of who does what, with the Máxima being responsible for transplants for pediatric oncological diseases and certain metabolic diseases. Leiden transplants many other non-malignant disorders. Caroline Lindemans says, ‘The procedures require great precision. If you want to do this well, you have to constantly evaluate very carefully what went well and what could be improved. These evaluations are a prerequisite for our accreditation. But we also do this because we want to achieve better and better results ourselves.’ Crucial for the evaluation of outcomes is a database with all data on how the children are doing. ‘Clinical research – continuously measuring what is happening – is an indispensable source for discovering trends and understanding why a child is or is not doing well.’

Effective cooperation
There are not many stem cell transplant surgeons in the Netherlands, Caroline says. ‘There are about six of us here and about the same number in Leiden. It is very useful to discuss all patients together. We do this monthly, in a similar way to the tumor boards here. Eight to ten children are always involved. You talk about how they are doing – including the deaths, which, unfortunately, also occur – and discuss children who may be eligible for a transplant. The collaboration has always been good in terms of content, but since the opening of the Máxima it has only got better.’

Better immune recovery
The outcome evaluation has revealed a striking trend: since the start of the SCT program at the Máxima, the survival rate of children has gone up. We’re becoming more alert to, and better at preventing, serious complications, such as infections. And the chemo prior to transplantation is becoming more effective, with fewer side effects. Caroline says, ‘We do this chemo beforehand in close cooperation with the pharmacy. The more precise the dosage, the greater the chances of success of the transplant. You disable the immune system very precisely in advance, so that the donor cells can quickly emerge after transplantation to completely replace the original defenses. We are seeing that this treatment has become less toxic and that the immune recovery after transplantation is actually better.’

Promising basic research
Unfortunately, what is not yet improving is the likelihood of the tumor returning, Caroline concludes. ‘So we are doing it more safely, but not yet effectively enough.’ New cellular therapies may make a difference. At the same time, preventing the graft-versus-host effect remains a major challenge. This is when the immune cells of the donor (graft) attack the cells of the host (patient). Caroline says, ‘I am very confident that we will learn a lot from research in order to be able to further improve the outcome.’

More information
At the stem cell transplantation center, the Princess Máxima Center performs stem cell transplants with a team of pediatric hematologists, pediatric immunologists and pediatric oncologists. The idea is that you attack a malignant disease, such as leukemia, by using the immune system of a healthy donor (allogeneic transplantation) or with processed stem cells from your own body (autologous transplantation, now also with CAR-T cells). The stem cell transplantation center can be found in the Hemato-Oncology department. Caroline conducts basic and translational research into the graft-versus-host effect at the Hubrecht Institute, Regenerative Medicine (UMC Utrecht) and together with medical immunologist Stefan Nierkens (UMC Utrecht.