Jakob Passweg
Professor and Head, Department of Haematology, Basel University Hospital, Switzerland; Past-Meeting President, EBMT
What sparked your initial desire to undertake a career in haematology, and then to pursue academic research exploring hematopoietic cell transplantation (HCT) outcomes?
This is interesting. I wanted to go into oncology and, by error, ended up in haematology. The first day that I got on the ward where the patients were, I was so fascinated that I never left.
You have co-authored over 450 publications throughout your career. Reflecting on this, what are the most significant advances you have seen towards improving outcomes for patients with haematological malignancies, who are treated with HCT?
Over my active career years, there has been enormous progress in many ways, not only in transplantation, but also in treatment for leukaemia and other cancers. It's an enormous field that is developing very rapidly, and the pace is actually increasing, not slowing down.
In the field of stem cell transplantation in particular, when I started, patients had to be younger than 50 years of age, and had to have a matched sibling. Now, we have tonnes of other donors, and unrelated donor transplantation has exploded. The registries now hold over 35 million people, and it is probably the largest volunteer organisation worldwide. The capacity to type donors and recipients has also tremendously improved, and has led to ever-improving results. Haploidentical transplantation and cord blood transplantation have also been developed. These did not exist when I started; marrow was the stem cell source, where you had to get the cells out of the marrow. Then peripheral stem cell donation came. These advances are just in the field of donor availability and stem cell availability.
There are also the graft-versus-host disease (GvHD) treatments that have been modified, the increased standardisation in the field for how we measure complications, and how we deal with infectious complications. For example, treatment has been revolutionised by many new antibiotics and antifungal treatments. So, my practice when I started was completely different from what it is now. Also, when I started, the average age of patients was around 35 years, and now it's going towards 65 years. The patients we treat are not the same.
Next to that are all the new drugs for leukaemia and myeloma, bispecific and monoclonal antibodies, and now cellular therapies. That's the major evolution. When I started out, bone marrow transplantation was the final treatment. Then came donor lymphocyte infusions, where you could add lymphocytes from the donor to treat leukaemia relapse; this was the first cellular therapy. The chimeric antigen receptor T-cell (CAR-T) treatments we have today are descendants of this revolution, somehow.
Do you feel that there are currently any unmet needs within the field that require a greater research focus to further improve patient outcomes?
In spite of the progress in GvHD prevention and diagnosis, it is still a major problem. The fact that we still lose patients to GvHD makes the treatment difficult, and treatment is not available to all patients. If we could administer immunologic anti-leukaemic efficacy without any risks, then that treatment would grow and expand even more. Currently, we have still a very dangerous and difficult treatment overall, in spite of all these improvements. In my opinion, the most difficult issue, and most important unmet need, is GvHD.
You previously served as the EBMT Congress President in 2012. Could you tell us what the role entailed, and the main objectives you aimed to achieve?
My first EBMT Annual Meeting was in 1994, and I haven't missed one since. As a Congress President, the budget has to be good. It has to make a benefit for the EBMT. There are many scientific societies who just maintain themselves, but the EBMT is a research organisation. It holds a database of over one million patients, whose data is used for research. Therefore, the EBMT is also a machine that advances clinical research. It helps young physicians, such as I was at one time, to start first projects; to advance with projects; and to make data available, because even now, it is a rare treatment, which means you have to pool data in order to come to meaningful conclusions, and to analyse relevant questions. The EBMT income has always been there to finance this research effort. It is most important to have a good programme for our meeting, in an attractive location so that people can enjoy being there, and at the same time, generate some income for the society.
In 2023, you co-chaired a round table discussion at the 49th Annual Meeting of the EBMT, on the topic of cord blood transplantation. What were the key take-home messages from this session?
Cord blood transplantation is a very interesting field. There is the issue of cord blood banking, including how much, who, and when. Cord blood transplantation had its most important days about 10–15 years ago, and has been decreasing since, because of the development of haploidentical transplantation. There are different transplantation techniques that are in competition with each other. At the same time, it is important to preserve cord blood transplantation because, for some patients, it is the only solution, particularly for paediatric patients. The question is, even if the number of cord blood transplants is decreasing, how can we maintain this technology, and its availability, for those patients who need it?
There are two aspects to this: unrelated cord blood banking, where you bank for other people, and direct cord blood banking, which means, if a female is pregnant, but has another child that has leukaemia, you can actually harvest these cells at birth for the sibling who is ill, and who might need those cells. In directed cord blood banking, the availability of the technology is also dependent on broader, unrelated cord blood banking.
This year, you are a recipient of the EBMT Distinguished Merit Award, in recognition of your outstanding contributions to the field of HCT, and to the EBMT, which will be presented at the Annual Meeting in April. Could you tell us about your work with the Activity Survey that led to you being bestowed this award, and what the award means to you?
It's a wonderful recognition, and I'm very grateful. It was a bit unexpected. I am enjoying getting this award. The more important issue to talk about is the Activity Survey, which was started in 1990, and is in parallel to the database.
The EBMT has a large database with extensive data. But then, the question is, how complete is this data? My predecessor, Alois Gratwohl, started in 1990, by contacting all centres performing transplants, whether EBMT members or not, in Europe and some associated countries. He asked them how many transplants they performed, and the indications for these in a one-pager. This can be easily filled out, and has more easily accessible numbers. This means you can check: if a centre reports 150 transplants, but only 75 were input into the database, this means the remaining half the transplants were not entered. You can then question why: is this by chance, or is this something systematic? This is important to validate the observational research of the EBMT.
At the same time, the Activity Survey has been used to monitor activity, including where transplants are done; the indication; why transplants are performed more frequently in some countries than in others; and why is an indication to do a transplant so much more frequent in one location than another? You can address all of these issues by having this information. The Activity Survey is like a mirror back to the Society, and it is published every year. The most recent survey that has just been completed is being published in the Bone Marrow Transplantation (BMT) journal. The EBMT has also started other projects, such as benchmarking, which looks at outcomes of patients and compares centres.
The way this works is that Helen Baldomero, who is a collaborator, and who is also getting an award with me, contacts centres. These centres send us all of the information, and it then takes the better part of a year to get it all in. Once everything is in, it is analysed, evaluated, written up, and then published, so there is always a little bit of a time pressure. However, if you were reporting back data that are 5 years old, it is no longer current. It's an important service to the community, and I think it's appreciated because it's almost always one of the most cited papers in the BMT.
I will be retiring in 2 years from now, in 2026, and Helen is also about to retire in 1 year; we're in the process of transferring this project, so it will continue after us.
Which sessions at the 50th Annual Meeting of the EBMT are you most looking forward to attending?
The most difficult thing is that there's so much in parallel, and you have to decide whether to go to an educational session, or a session where new research is being presented.
This year, obviously, it's the opening session, because that's where I get the award, so that's an easy answer!. But otherwise, there are just so many different sessions. Where we have to improve is maybe, now everything is recorded, for recordings to be available for a prolonged time, so you can go back and watch sessions that you didn't have the chance to go and see.
The EBMT has a core set of values, and seeks to advance stem cell-based treatments for patients with blood-related disorders. How has the EBMT impacted your research and clinical practice?
Not all of my papers have been with the EBMT, but the majority have. My career would have been completely different without the EBMT, which has facilitated my career. It's a great community; we’re all friends, and we have done a lot together. We have published together, and have helped each other in advancing our careers, so it's a huge machinery to actually get ahead; not only as a society and for the benefit of patients, but also professionally and personally.
Are there any innovations on the horizon that you think will have a significant impact, and that you are excited to see materialise clinically?
The biggest growth right now is in cell therapy, which is like an offspring of stem cell transplantation. There is also tremendous growth in the CAR-T treatments that use CD19 as a target for B-cell malignancies, and B-cell maturation antigen as a target for myeloma, which is also a B-cell malignancy. This field is expanding and exploding, not only in clinical knowledge of how to treat patients, what to expect, the complications, and how to deal with them; but also in new developments, and that is where I'm looking forward to a lot of new things. I hope that we will make progress in the field of GvHD, for which there is also some developments on the horizon.
Stem cell transplantation is a rather coarse and onerous treatment for patients. If other treatments come around that are easier for patients, then that's good.
There are other developments on the horizon, such as bispecifics for myeloma and lymphoma, etc., that could replace current treatments. One of the things my generation witnessed is that 20 years ago, between 1990–2000, chronic myeloid leukaemia was the most common indication for transplantation. When drugs came around that treated the disease, suddenly, treatment with transplantation was only needed in a minority. So, 20 years ago, 30–40% of the allogeneic transplants were for chronic myeloid leukaemia, and now it's 2–3%, which means it's still needed, and is still a technology that is good for certain patients, but only for a small minority. For the majority, this treatment has been replaced by something much easier.
The hope is that we will find more and more of these easy treatments. Right now, for young colleagues who are interested to go into this field, I still tell them to go into it, because they’re not going to be replaced that fast; it's one of the most innovative fields in medicine.
Editorial Team: 
Distinguished Merit Award 2024