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Hematopoietic stem cells: transplant of life



Professor Tayfun Gungor and his team have helped hundreds of children suffering from chronic granulomatous disease (CGD) to reclaim their aspirations for the future and for a normal, healthy life. They have pioneered a method of hematopoietic cell transplant that has been recognised by the scientific community as one of the safest and most effective in the world.


–  Professor Gungor, I know that during the pandemic you have been very busy and have managed to bring children to Switzerland for treatment, despite the restrictions. What kind of cases were they?

– The past months have been extraordinary for all of us. However, at the Children’s Hospital Zurich, the well-being of the young patients is always the center of attention. This is why we have made every effort to ensure that our foreign patients find their way to us where we can start urgently needed treatments. We are a transplant center for hematopoietic stem cells and we specialize in particular diseases of the immune system. At the moment we have three patients from Russia with primary immunodeficiency chronic granulomatous disease (CGD). They have been given transplants of hematopoietic stem cells from unrelated matched volunteer donors.

– Is it a genetic condition?

– Yes. It is quite rare, but not extremely rare – it is diagnosed in one in every 200,000–250,000 people. It is not an immediately lethal immunodeficiency – the patient can survive the first decades of life, but usually they are very prone to invasive bacterial and fungal infections and autoinflammatory problems of the intestines and the lungs, so the quality of life is very much impaired. Patients grow less than their peers and have problems at school because of their many hospitalizations and operations. In the last 20–25 years stem cell transplants have been the main curative treatment for this condition. They can cure all pre-existing infections and problems and normalize the quality of life and life expectancy (which is impaired in people with this disease – many patients die between the ages of 10–30). So it is a curative treatment, but it is also a bit risky.

– How does this procedure work?

– We transfer blood stem cells extracted from the bone marrow, peripheral blood or sometimes from the umbilical cord, from related or unrelated donors. It looks like blood, but contains what you might call the ‘mother cells’ for all the blood and immune cells. The cells are transferred from one person to another; they start working in the new body and become part of the recipient. That is the most exciting part of this procedure. It’s not like organ transplants, when you transplant a kidney or a heart and you have to cope with rejection problems and need immunosuppressive treatment your whole life. In hematopoietic stem cell transplants you can usually stop all medications after six months because of tolerance development. You basically transfer two organs – the immune and the blood system – to another person, and that person becomes completely independent from blood or immune support or other supporting therapies.



– How long does the transplant take?

– From one and a half to two months. First, we insert the catheter for the blood sampling and infusion of the bone marrow cells. Then there is the preparation time, called conditioning. We calm the immune system of the recipient and destroy the majority of the hematopoietic stem cells of the recipient to make way for the new ones and make sure there’s no rejection. Then you need two to four weeks for the new cells to start producing blood and for the immune system to start functioning. At this point there is a risk that the cells will become aggressive towards the recipient or the recipient’s body will reject them. That is dangerous. At the point of immunity reconstitution, it is very important to eliminate the risk of infections and ensure that some viral infections the patient has had in the past are not reactivated; many of us have viruses in our body, but they are suppressed by the immune system. At this time the immune system is vulnerable, but it grows stronger, and after six months it is almost completely normalized.

– Why would you say that people from all over the world come to your team for help?

– They come to us because they trust us. They know that we employ specialists who apply innovative methods and do their best to help sick children. The Children’s Hospital in Zurich is a leading institution for hematopoietic stem cell transplantation. Thanks to our well-known research department, we have been able to improve the therapies in recent years. We are doing pioneering work: for example by reducing the toxicity of the therapies. One of the side effects of high-dose chemotherapy is infertility, but our method helps women and men to remain fertile. We published a wellcited article about our innovative method in The Lancet medical journal (Gungor et al., 2014). We also work together with pediatric institutions worldwide, many of whom now use our effective treatment methods.

– Immunodeficiency is difficult to diagnose. Have you had any cases when the patient should have been diagnosed much earlier?

– You’re absolutely right. This disease can be hiding behind some nonspecific symptoms, or you might misdiagnose it. You might see some rheumatological problems or intestinal problems and not see the underlying mechanism. I’ve encountered this several times. Just recently I saw a case where CGD was not diagnosed in 2000 by a gastroenterologist, and the patient only received the correct diagnosis and a transplant 13 years later. The patient sued this gastroenterologist. Unfortunately, a delay in diagnosis is still not uncommon. It can be diagnosed rather quickly allowing for two conditions: the doctor has to be qualified to think of this diagnosis, though it is indeed rare, and he or she has to have the resources to perform a specific test – you need a good immunological laboratory with trained staff. There are standardized tests, but they are not available in every laboratory.

– What is the average age of your patients and what is the best age of a patient to perform this procedure before it starts affecting quality of life?

– Formerly, most patients were of primary school age or even in adolescence because of that diagnostic problem. Now the patient gets diagnosed earlier, at the age of 2 or 3. And we see them before they go to school. That is probably the best age for a transplant. It’s always a sticky question: if the child is diagnosed as a baby, should you carry out this procedure on an infant? Our opinion is that if it’s not crucial, it’s better to wait one or two years. The transplant requires lengthy hospitalization, which is a traumatizing experience for a baby. So this little delay allows the patient to get some emotional skills and go through all the developmental stages that children go through in their first year. If the diagnosis comes a bit later, I recommend doing the transplant before puberty, as this is also a difficult period in life – adolescents are often confused and their psyche is a bit distorted. During this period children develop so quickly that they become more sensitive to toxicity. It is known that transplant results get about 10% worse after the age of 14 years. It is also possible to carry out the transplant on an adult, but usually the disease burden is higher and there are problems with different organs. Adults are also more prone to complications like graft failure, graft rejection, and graft versus host disease. Of course in some cases, such as a lifethreatening infection, you just have to do it. I’ve seen fathers of families having to decide whether they want to go for the transplant with a 20% chance of dying, or to continue to live their life with conventional treatment. In children, the chance of a full recovery is 90–95%.



– So you are saying there is always a discussion and an evaluation of the chances…

– Yes. If the patients are asymptomatic you have to be very confident to offer potentially risky treatment. But when patients develop and have already suffered some consequences, their parents will more easily make the decision about the transplant. They know that their children will have restrictions their whole life: they won’t be able to choose the profession they want, and they will have reduced life expectancy.

– How can parents of infant children spot the symptoms of this condition and approach the doctor?

– It could be some problems with the skin right after birth – for example, staphylococcus bacterial infections. If an infant develops lymphadenitis, an infectious swelling of the lymph nodes, it might be worth consulting a doctor and asking for analysis. Sometimes inflammatory bowel disease – colitis or Crohn’s disease – can be an indicator of CGD. And, of course, if the child has inflammatory lesions and infections of the lungs and the liver, abscesses, or granulomas, you should check for CGD.

– How many people are working in your department and what are your main challenges as a team?

– This treatment is very timeconsuming and there are a lot of decisions to make during the process. Imagine you are in the jungle, in a dangerous place, and you have to guide your companion through it. You have to instill confidence in the parents, who are also very much under pressure. You need a good nursing team because you have to pay a lot of attention to the patient, day and night. We have about 16 nurses. You also need collaborators from other departments – surgeons, anesthesiologists, etc. You need coordinators – someone to oversee searches for donors, hospitalizations and discharges. It’s like a dispatcher at the airport. And you have to document everything you do for scientific reports and for the authorities, because we are dealing with human cells, with donors and recipients. We are also under the surveillance of international inspectors from hospitals abroad. It’s been tough, the more than 20 years that I have been doing this, but of course it is worth it. Today, with hematopoietic cell transplants we can fully cure the patient, and they are no longer dependent on drugs. This is very satisfactory.

– Could private donations help you in any way?

– Thanks to donors we can continue making progress in research and thus develop new and better therapies for our young patients. Two thirds of the research at the Children’s Hospital is financed by donations and third-party funds. It is also donors who make it possible for us to treat seriously ill children from abroad such as Russia. Thanks to these generous people, we can provide our patients with the best possible treatment. I feel great gratitude to the donors. They give sick children and their families hope for a better future.


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Support the Children’s Hospital in Zurich. Donate today to help seriously ill children who depend on a stem cell transplant. With this, you are giving them a second chance for a brighter future.

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Note: Stem cells


Professor Tayfun Gungor



Medical school in Frankfurt/Main (Germany), education in Pediatrics and Pediatric hematology/oncology/ immunology (1988-1996). After board certification in Pediatrics (University Children`s Hospital, Frankfurt/Main, Germany) post-doc time in Ulm/ Germany and education in Stem cell transplantation for malignant and non-malignant diseases (1996-1997). In 1997, consultant at the University Children`s Hospital Zürich/Switzerland (Division of Immunology, Hematology & Stem Cell Transplantation). In 1998, Pediatric Rheumatology diploma (Rene Descartes University, Paris, France). In 2000, diploma in Cellular Therapy (University of Haute-Alsace, Mulhouse, France), takes over leadership of the Stem cell and immunology laboratory. Swiss board certification (FMH) in Pediatric Hematology/Oncology (2003) and Clinical Immunology/Allergy (2004). Development of a reduced-intensity conditioning regimen to cure chronic granulomatous disease (CGD) (Lancet 2014). Active member of the Inborn Errors and board member of the Pediatric Diseases Working Parties of the European Group of Bone Marrow Transplantation (EBMT). In 2008, Senior Lecturer and in 2012 Titular Professor of Pediatrics and Stem cell Transplantation at the University of Zürich, Switzerland. In 2014, Clinical Transplantation award of the University Hospital Zürich. Tayfun Güngor has published 172 research issues with 4571 citations (10 Aug 2020).

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