HISTORY EUROTRANSPLANT

Transcription

1 HISTORY EUROTRANSPLANT HISTORY 81

2 TIMELINE Year Event 1967 Creation and launch of Eurotransplant by Prof. Jon J. van Rood (cooperation between centers in Austria, Belgium, Luxemburg, Germany, the Netherlands and Switzerland) 1968 First Eurotransplant Annual Meeting (6 June 1968, St. Lucas Hospital, Amsterdam) 1969 Legal founding of Eurotransplant Foundation before a Dutch notary 1981 First Eurotransplant Winter Meeting (Fügen, Austria) KIDNEY 1967 First kidney transplant in Eurotransplant. The actual first kidney transplant in the ET region, before the founding of Eurotransplant, took place in Introduction of the EuroCoIIins preservation solution as the standard for organ preservation 1981 Introduction of Cyclosporin-A (which significantly increased kidney graft survival) 1985 First Donor after Circulatory Death (DCD) transplantation in Eurotransplant (kidney) 1988 Start of Acceptable Mismatch programme (AM) 1988 The University of Wisconsin (UW) cold storage solution gradually replaced EC solution as the preferred preservation fluid for abdominal organs 1995 First international workshop on DCD in Maastricht, identified four categories of DCD 1996 Introduction of Eurotransplant Kidney Allocation System (ETKAS) 1999 Introduction of Eurotransplant Senior Program (ESP) LIVER 1972 First (whole) liver transplant in ET 1988 First split liver transplant in ET 1996 Introduction of center-oriented liver allocation system 2000 Introduction of the Child-Turcotte-Pugh score for liver allocation 2006 Introduction of the Model for End-stage Liver Disease (MELD) score in Belgium, Germany, the Netherlands, Austria, Croatia and Slovenia; based on center-oriented allocation HEART 1981 First heart transplant within Eurotransplant 2000 Introduction of Eurotransplant Thoracic Allocation System (EThAS) 2011 Start of development of benefit-based heart allocation system (CAS: Cardiac Allocation Score) COMBINED ORGANS 1983 First combined organ transplant within Eurotransplant LUNG 1987 First lung transplant (double and single) in Eurotransplant 2011 Introduction of Lung Allocation Score (LAS) in Germany (benefit-based lung allocation system) 2014 Introduction of Lung Allocation Score (LAS) in the Netherlands PANCREAS 1979 First pancreas transplant within Eurotransplant 2003 Introduction of Eurotransplant Pancreas Allocation score (EPAS) INTESTINE 1989 First intestine transplant in Eurotransplant (2nd transplant not until 1997) LEGISLATION 1982 Austria - Federal Law No. 723 (Hospitals Act KAG) (no specific law on organ donation & transplantation) Presumed consent 1982 Luxembourg - Act on substances of human origin Presumed consent 1986 Belgium - Act on Procurement and Transplantation of Organs Presumed consent 1988 Croatia - Act on Procurement of Organs Presumed consent 1996 The Netherlands - Organ Donation Act Informed consent 1997 Hungary - Act on Health, Chapter XI on organ donation and transplantation (Sections ) Presumed consent 2000 Slovenia - Organ Donation Act Presumed consent 2004 Croatia - New Transplant Act Presumed consent 82 EUROTRANSPLANT

3 EU DIRECTIVES 2004 Standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells 2007 Organ donation and transplantation: Policy Actions at EU level outlining: increasing the quality and safety of organs, improving organ availability, increasing efficiency and accessibility of national transplant systems 2010 Directive 2010/53/EU: standards of quality and safety of human organs intended for transplantation PROJECTS 1991 Introduction of European Donor Hospital Education Program (EDHEP) EFRETOS European Framework for Evaluation of Organ Transplants FOEDUS - Participation of Eurotransplant in Work Package EUROSTAM - Participation of Eurotransplant in Work Package ACCORD Collaborating partner in Work Package EDITH Participation of Eurotransplant in Work Package 6 OTHER 1988 PIONEER Electronic matching system operational 1989 Foundation of Bio Implant Services (BIS) as a subsidiary of Eurotransplant 1991 Former East Germany joins Eurotransplant 1996 PIONEER Electronic matching system replaced by ENIS (Eurotransplant Network Information System) 1997 Foundation of Netherlands Transplantation Foundation (NTS) 2000 Introduction of data warehouse reporting system in Eurotransplant 2000 Slovenia becomes a member of Eurotransplant 2007 Croatia becomes a member of Eurotransplant 2012 Eurotransplant introduces online statistics library 2013 Hungary becomes a member of Eurotransplant 2016 Start of development of CORE (successor of ENIS system) The expressiveness and symbolism of the human hand inspired sculptor Rodin, and Eurotransplant's founder Jon van Rood. Hands which give, cherish and heal. This sculpture remains at Eurotransplant's office in Leiden to this day DIRECTORS/MANAGEMENT TEAM ET ( ) Year Function Henk Schippers first Director of Eurotransplant Bernard Cohen General Director of ET 1985 Frans Claas Head of Eurotransplant Reference Laboratory (ETRL) Guido Persijn Medical Director (joined ET in 1971 as student-assistant in charge of allocation) Illias Doxiadis Managing Director ETRL Wim van Zwet Head IT, combined in 2005 with Head Finance Arie Oosterlee General Director Axel Rahmel Medical Director 2013 Sebastiaan Heidt Managing Director ETRL 2014 Serge Vogelaar MT-member - Manager Allocation (joined ET in 2008) 2014 Ton Valkering MT-member - Manager Finance/IT (joined ET in 2008) 2014 Undine Samuel Medical Director/Manager Allocation Development 2015 Peter Branger General Director HISTORY 83

4 TURNING FIFTY LOOKING BACK ON A DYNAMIC HISTORY The history of Eurotransplant in a nutshell shows a sequence of scientific landmarks, dogged scientists, altruistic donors and families, desperate patients, politicians and energetic paramedics, nurses, doctors and surgeons. It all started in Leiden IT WAS IN THE AUTUMN of 1967 that the Blood Bank at Leiden University Hospital (AZL) received a phone call from Leuven. A helicopter was on its way to AZL, carrying a kidney that had been removed from the body of a traffic victim. Could Jon van Rood and his team ensure that it was transplanted into a suitable patient? Shortly before, at the Third Histocompatibility Workshop in Turin, Van Rood had launched his plan for international cooperation between transplant centers, with the aim of selecting the best potential recipient when a donor kidney became available. The phone call from Belgium led to a slight panic. The staff at AZL did have a list of kidney patients, whose tissue antigens had been serologically determined. Tissue antigens are proteins that are present on the surface of all cells and tissues of a patient and which need to match the antigens of the new kidney as closely as possible. But the tissue antigens of the kidney coming in on the helicopter still had to be checked, or typed as it is called. Also, a crossmatching test had to be carried out to check that the selected patient s blood contained no antibodies against the donor s blood. The Blood Bank staff at Leiden came to realise that it would take a lot of organising skills to make a success of the proposed international exchange organisation named Eurotransplant (ET), but good progress was quickly made. ET mediated in the transplantation of 11 kidneys in 1967, and in 1968 this rose to 60 and then steadily increased. Van Rood would later characterise the way Eurotransplant made its start as running before you can crawl. After a while, the organisation also began to mediate in the exchange of other organs. Half a century later, it has become a robust organisation that has been commissioned by the governments of its member states to arrange the allocation of the organs of deceased donors to patients on the transplantation waiting list, in order to coordinate the demand and supply of human organs for transplantation. This chapter describes how Eurotransplant began, and what steps helped to ensure that it is able to celebrate its 50th anniversary in Healthy diversification Eurotransplant s history is marked by different kinds of milestones. One concerns the years in which the organisation first started to mediate the exchange of a new type of organ. ET MEDIATING IN SINCE KIDNEY 1967 LIVER 1979 PANCREAS 1980 HEART 1982 HEART / LUNG (Multi-organ donor) 1984 LUNGS 1987 INTESTINE 1997 Another kind of milestone is the joining of new countries housing the participating transplant and tissue typing centers. Eurotransplant started with the Netherlands, Belgium and Germany, soon to be joined by Austria and later on Luxembourg. (Until 1974 there was also cooperation with the National Reference Center in Geneva, Switzerland).Two years after the fall of the Berlin Wall in November 1989, former East Germany joined up. Slovenia became a full member in 2000, followed by Croatia in 2007 and Hungary six years later. Today ET can be truly called a transnational organisation. A third kind of milestone relates to organisational development. The first of these was of course the very act of founding Eurotransplant by Jon van Rood in Leiden in The next major step was the appointment of Henk Schippers as general director in Physician Guido Persijn joined in 1971 as junior medical officer and was later appointed general director alongside economist Bernard Cohen, who had succeeded Schippers as managing director in All of this took place in the overcrowded building known as Building 23 of the old Leiden University Hospital (AZL). In 1985 Eurotransplant moved to a newly built complex housing the AZL, now known as the Leiden University Medical Center (LUMC). But in 1995, all independent foundations were ordered to leave the main hospital building. The Board of Eurotransplant initially objected to this, as they expected that the synergy with LUMC would be sorely missed. It soon turned out to be a blessing in disguise, however. The organisation quickly became more independent, and its new premises at 100 Plesmanlaan in Leiden actually offered far better possibilities. 84 EUROTRANSPLANT

5 Alouette II helicopters owned by the Belgian Army regularly flew cool-boxes containing organs in order to transport them as quickly as possible to the operating theatre and recipient. June 1970: A pilot carries a box containing a kidney from Belgium to be flown to Berlin, Germany. First his documents are checked by the airport customs officer. The second cool-box also contained a kidney from Belgium, which was flown in another helicopter to Groningen in the Netherlands PHOTOS BELGIAN DEFENCE CENTER FOR HISTORICAL DOCUMENTATION Eurotransplant was granted ISO certification in 2001, another milestone in its process of professionalisation. The two directors Persijn and Cohen, who had led Eurotransplant for 30 years, both resigned in 2005, after which a new directorate was appointed. Most importantly, the development of Eurotransplant is directly based on the progress of medical science itself. To understand this, one has to look back at the medical breakthroughs in the years since Eurotransplant was founded. After organ transplantation had developed from an experimental procedure to a validated treatment, it became a true icon of high-tech medical intervention. The demand for donor organs rose gradually at first, but soon grew exponentially. One problem in transplantation medicine is that the human body has a very efficient immune system, built to eliminate any foreign invaders, whether they are pathogens or a foreign organ. The immune system distinguishes between self and non-self, and anything that is non-self triggers an immune response resulting in rejection. Initial attempts at transplantation tried to avoid rejection of the donor organ by transplanting kidneys from living related donors. At first, these transplantations were only done between identical twins, later expanding to all close relatives. These operations were reasonably to very successful, whereas transplanting kidneys from non-related, deceased donors initially yielded poor outcomes. Successfully transplanting foreign kidneys (allografts) OVERVIEW OF LANDMARKS IN THE EARLY HISTORY OF ORGAN TRANSPLANTATION 1881 Macewen (UK) bone transplantation 1905 Zirm (Austria) 1900 Landsteiner (Austria/USA) 1915 Lewisohn (USA) 1944 Kolff (Netherlands/USA) 1951 Medawar (UK) 1954 Murray (USA) 1958 Máthé / Van Bekkum (France/The Netherlands) 1958 Dausset (France) 1962 Van Rood (The Netherlands) 1962 Ross (UK) 1963 Hardy et al. (USA) 1963 Starzl et al. / Calne (USA) 1967 Van Rood (The Netherlands) 1967 Barnard (S. Africa) cornea transplantation discovery of ABO blood types blood transfusion artificial kidney / dialysis transplant immunology first successful kidney transplant bone marrow transplantation first antigen of HLA system [HLA-A2] HLA system, systematic approach cardiac valve replacement with homograft lung transplantation liver transplantation founding of Eurotransplant heart transplantation 1978 Borel + Calne (Switzerland/UK) Immunosuppressive drug cyclosporine N.B.: Landsteiner, Medawar, Murray and Dausset were awared a Nobel Prize HISTORY 85

6 became possible after researchers discovered that organs contain certain antigens proteins that trigger the production of antibodies which occur in many variants among the population. Selecting a donor whose tissue antigens closely match those of the patient prevents the occurrence of a severe rejection reaction. This process of successfully matching donors with recipients is the ultimate justification for the creation of Eurotransplant and other organ exchange organisations. In fact, Eurotransplant was the first large-scale effort in the world to implement transplant immunology and immunogenetics in clinical organ transplantation. From tissue antigen to leucocyte As we have seen above, tissues contain cell-surface proteins, called antigens, that trigger the production of specific antibodies when a foreign organ is transplanted. Preventing rejection necessitates serological matching, but it is difficult to examine a solid organ without damaging its tissues. The crucial discovery that enabled matching that is, ensuring that a donor organ is suitable for a specific patient was that these characteristic antigens are also present on the leucocytes (white blood cells). This is why the antigens checked for in tissue typing are known as HLAs, Human Leucocyte Antigens. Thus, research in the 1950s and 1960s found that a person s leucocytes carried antigens that triggered an immune response, and that were characteristic of all organs of that particular person. This meant that in matching donor organs with patients, it was enough to characterise ( type ) the leucocytes in their blood serum in order to prevent rejection of the transplanted organ as much as possible. This process of typing requires special sera. The breakthrough that enabled Jon van Rood to put Leiden on the map as a center of excellence in transplant immunology was that of developing tissue typing sera and making them available. The key to matching kidneys was the investigation of the HLA system, and thus it is with the leucocytes that we must start our story. SELF AND NON-SELF Dutch immunologist and pioneer Jon van Rood is founder of Eurotransplant and was for almost three decades its president. He made crucial contributions to unravelling the HLA system, a breakthrough development in the history of transplant medicine. He was awarded numerous prizes and distinctions IN 1953, JON VAN ROOD made his entrance at the Leiden University Hospital as a trainee in internal medicine. After just a year he was appointed head of the Blood Bank, a position he would continue to fulfil for almost four decades.. Context Before discussing Jon van Rood s breakthrough research, which would lay the foundations for Eurotransplant, let us first take a brief look at the scientific context in which he worked. Peter Medawar, originally a zoologist, worked during World War II at the 86 EUROTRANSPLANT

7 Lower arm with skin transplants grafted onto it using the Rapaport method; from an experiment by Van Rood in the 1960s Jon van Rood using a microscope to study skin grafts on the arm of Ab Struyvenberg, a fellow founder of Eurotransplant Leucocytes (left) clump together agglutinate in the presence of antiserum (right) Glasgow burns unit, where he used experimental skin transplantation techniques to treat wounded RAF pilots. From his research he concluded that tissue transplantation between individuals of the same species (whether humans or animals) could lead to immunological reactions, due to genetic differences. These differences were expressed in different proteins (antigens) on a person s white blood cells (leucocytes). His studies greatly inspired Van Rood. At the Leiden Blood Bank, research focused on the question what role the leucocytes played in reactions to blood transfusions (which are, in a way, also a kind of transplantation). In 1954, Jean Dausset of the Hôpital Saint-Louis in Paris had made an important discovery, namely that leucocytes could trigger the formation of antibodies if they are identified by the body as foreign, or non-self. Van Rood and his co-workers at the Leiden Blood Bank found that similar antibodies could be produced in a woman s body during pregnancy, against the specific antigens of the father (paternal antigens) located on the child s leucocytes. Further widening the research, they discovered that the leucocyte antigens could be categorised into several groups with the help of specific sera. Jon van Rood described this in his 1962 PhD thesis entitled Leucocyte Grouping, a Method and its Application. The Leiden research group now had an experimental system to test whether the serum of a woman who had been pregnant contained so-called leucocyte agglutinins. Their presence could be measured by a cross-test, performed by mixing the sera of women who had just given birth with the white blood cells of randomselected blood donors, and plotting the results. Interpreting these data with the help of a computer showed that the leucocyte groupings really constituted a system. Studying tissue compatibility in humans, however, presented a practical problem. This was solved by American researcher Felix Rapaport, who designed a simple technique to study transplant reactions, by not removing a complete piece of skin but only scraping a small patch of skin and grafting a skin transplant onto it. The result was an easily reproducible experimental model for transplantation studies in humans, which was to be used also by Van Rood and co-workers. The turning point The 1960s saw worldwide efforts to finally solve the problem of how to apply the newly gained knowledge of tissue compatibility in clinical practice. In 1964, immunologist Bernard Amos from the National Institutes of Health in Bethesda, Maryland (USA), decided to organize the first congress on histocompatibility (the compatibility of tissues). His aim was to create more unity in the laboratory tests and tech- HISTORY 87

8 niques used, which at the time showed a wide variety. The next histocompatibility workshop was held in Leiden one year later. Van Rood had available a set of sera typed for some well-defined antigens. This finally delivered the format that became the international standard for histocompatibility hands-on workshops. In 1965 another workshop in Leiden proved a true turning point because during this meeting, family data obtained by Van Rood s research group and population data from Jean Dausset s Paris group provided preliminary evidence that most of the antigens recognised belonged to a single genetic system. With the proper typing technique in place, it was now possible to start experimenting with the clinical transplantation of human tissue. This was an extension of similar experiments with monkeys in the Biomedical Primate Research Center in Rijswijk. These studies corroborated Medawar s earlier observations in human skin grafting. The real thing : HLA typing of kidneys There was now conclusive evidence that the HLA system was important for skin transplants; but was it also for kidney transplants? In 1966, English surgeon Michael Woodruff, working in Dublin, who had discovered some specific antibodies during his study of the immunological aspects of clinical transplant surgery, invited Van Rood to test in kidney-transplanted patients if HLA compatibility between the donor organ and the recipient correlated with prolonged rejection-free graft survival. These investigations had to be done on site in order to do the leucocyte typing, because cells had to be fresh. Van Rood did these studies in Dublin, and later performed similar tests on other kidney-transplanted patients during a tour of various cities: Brussels, Leuven, Boston, Minneapolis and Denver. The final conclusion was clear: the variety of antigens recognized by leucocyte serology were indeed transplantation antigens crucial to kidney graft survival. The concluding data were presented at the International Congress of the Transplantation Society in Paris in June No limits The complexity of the HLA system made it necessary to be able to match a donor kidney with a large pool of potential kidney transplant recipients. Van Rood definitely did not lack ambition. It seemed self-evident to him to look across national borders and hence to initiate international cooperation so as to include as many potential recipients as possible in the search. He proposed his idea of a cross-border organ exchange organisation at the Third International Histocompatibility Workshop in Turin. His original plan had been to launch the idea in the context of the presentation he was going to give there. On the advice of a Dutch colleague, however, he presented the idea in a separate eyecatching abstract published in the workshop proceedings: A proposal for international cooperation in organ transplantation: Eurotransplant. Starting from scratch In its first operational year, 1967, the Leiden office performed the typing and matching for 11 donor kidneys. The next year already saw this number rise to 60, and by 1970 over 1500 tissue typings were carried out for 1080 registered patients, at the request of 68 cooperating dialysis centers in the Netherlands, Austria, Belgium, Germany, and Switzerland. These typings were performed in 32 laboratories, spread over the participating countries. To streamline the operation and enhance the quality of the typing procedures, a National Reference Center was designated in every member state, to make the contacts with Eurotransplant s central office more efficient. This rapid growth of activities soon created the need for a more formal basis for Eurotransplant. De Stichting Eurotransplant Foundation was legally founded on 12 May 1969 before Dutch notary Scheltens in Leiden, in the presence of, and at the initiative of the following three witnesses: Dr. Jon van Rood (then head of the Immunohaematology Department of the AZL), Dr. Ab Struyvenberg (internal medicine specialist and at that time head of the Kidney Disease Department of the AZL), and Mr.B. Jansen (company lawyer). The following centers are mentioned in de foundation charter as supporting the aims and objectives of Eurotransplant: Tissue typing research by Aad van Leeuwen and Jon van Rood Jon van Rood s world tour to evaluate the effect of tissue typing on kidney transplant survival 88 EUROTRANSPLANT

9 1 Sint Lucas Ziekenhuis (Amsterdam) 2 Wilhelmina Gasthuis (Amsterdam) 3 Central Laboratory for Blood Transfusion of the Red Cross (Amsterdam) 4 Centre de Transfusions, Centre Albert Hustin, Hôpital Universitaire Saint-Pierre (Brussels) 5 Chirurgische Universitätsklinik (Bonn) 6 Hôpital Universitaire Brumant (Brussels) 7 Academisch Ziekenhuis Gent 8 Academisch Ziekenhuis Groningen 9 Chirurgische Klinik der Medizinische Hochschule, Oststadt Krankenhaus (Hannover) 10 Medizinische Universitäts Klinik Köln-Merheim (Köln) 11 Cliniques Universitaires Saint Pierre (Leuven) 12 Academisch Ziekenhuis Sint Rafael (Leuven) 13 Academisch Ziekenhuis Leiden 14 Hôpital Universitaire de Bavière (Luik) 15 Sint Radboud Ziekenhuis (Nijmegen) 16 Stads en Academisch Ziekenhuis (Utrecht) NEEDLE IN A HAYSTACK? Matching donors and recipients is the core business of Eurotransplant. Essential prerequisites in allocation are transparency, objectivity, reliability and accountability. Eurotransplant has faithfully stuck to these values throughout the past 50 years WITH THE RELATION between HLA compatibility and the survival of transplanted kidneys and thus ultimately of the patient proven, Eurotransplant faced the operational challenges of finding a suitable potential recipient when a donor kidney became available. The removal and transport of the donor kidneys were arranged by Eurotransplant s desk staff, who contacted the doctor treating the selected patient. This often took several phone calls. In addition, all kinds of other logistical aspects needed to be arranged. All this was done from the office at the Leiden Blood Bank during office hours. But the work had to continue in the evenings and at night, for which medical students served as duty officers. They slept in a small room at the Blood Bank that had been fitted out with a computer terminal on which they could match the donor organ with a patient. Later, beepers were used to call up the duty officers. The matching was done on the basis of HLA compatibility. The more research was done into this system in the 1970s, the more complex it turned out to be. Biological complexity necessitates cooperation The large number of variations in HLAs (called polymorphisms) results in innumerable combinations; by 1972, 8,000 possible combinations had already been identified. In order to increase the chances of finding an optimal ET s director Bernard Cohen himself was also sometimes on duty as a match maker. Here he is shown with the telex next to the bed for night duty In the foundation charter an Executive Board (responsible for the day-to-day management) was appointed, consisting of Van Rood, Struyvenberg and Jansen. They would act on behalf of the 16 cooperating centers. In the (near) future, all centers were to be invited to designate a person representing that center, thereby forming a new Board of Management. The formation of this board would take several years. HISTORY 89

10 match, a database containing the HLA characteristics of as many potential recipients as possible was created. This was achieved by the cooperation between dialysis centers (about 70 by 1972), transplant centers and tissue typing laboratories in the ET member states. Eurotransplant s task was threefold: it had to manage the data of potential recipients (who were on the waiting list) and make sure that their current serological data were available; upon being informed that a donor organ was becoming available, the donor s blood type and tissue characteristics had to be determined as quickly as possible; and third, these data had to be transferred by telex or phone to the Eurotransplant office, where a computer selected a patient who had the best match in terms of tissue characteristics and a compatible blood type. Matching donor and potential recipient The procedure in the 1970s involved compiling a set of about 40 potential recipients with the best matches who were at the top of the waiting list, within minutes after a donor was reported to be available. The process of allocating the donor organ to a specific patient started by contacting the doctor treating the patient at the top of the list of potential recipients. Crossmatching tests between donor and potential recipient were then done at the tissue typing lab. If the result was negative (that is, no immune reaction when blood of the donor and the recipient were mixed) and the patient s doctor reported their willingness to accept the organ, it was time to arrange the transport of the donor organ to the patient. The organ would be packed in a box, bathed in saline and cooled with crushed ice. This made for a hour time slot, which meant that the organ could be transported by car or on an ordinary scheduled flight. Of course, it was important to know whether the Eurotransplant procedure involving HLA typing and matching actually worked. This would have to be proved by comparing the percentages of surviving kidney transplants after 12 months allocated via the Eurotransplant system with the survival percentages achieved without tissue matching in centers elsewhere in the world. The comparison showed that the ET method achieved a superior 1-year graft survival of 64%, against 51% worldwide. Further development of HLA matching, e.g. the introduction of matching primarily on HLA-DR, and the development of better immunosuppressive medication, led to even better outcomes in the following years, resulting in very favourable survival rates for transplanted kidneys. A considerable impact was made by the introduction of the immunosuppressive agent cyclosporine. This compound, when it came available around 1980, was seen by many as the magic bullet of transplant medicine. Even though expectations were tempered later on, cyclosporine shook up the world of transplantation. This was also true for Eurotransplant, as the next chapter will show. In exceptional cases, a donor organ was transported by private plane, but mostly it was carried in the cabin of a scheduled flight, in the custody of a crew member. A donor kidney in a polystyrene transport box. 90 EUROTRANSPLANT

11 Numbers of patients registered for kidney transplantation greatly increased between 1980 and 2004, due to the success of cyclosporine THE PRICE OF SUCCESS The advent of cyclosporine marked a watershed in organ transplantation. It transformed the transplantation of deceased donor organs from a daunting intervention with an unpredictable outcome, into a routinely and reliable procedure WORK AT EUROTRANSPLANT underwent a radical change around It had taken quite a while before transplantation techniques for organs other than kidneys became clinically feasible. In 1979, Eurotransplant received the first request to mediate in finding a suitable potential recipient for a donor liver. The first pancreas followed a year later, and the first heart in DYNAMICS OF THE EUROTRANSPLANT KIDNEY WAITING LIST AND TRANSPLANTS First post mortem in LA: First living rated in LM: waiting list kidney patients living donor transplants NEW AGENTS FOR IMMUNOSUPPRESSION deceased donor transplants The effect of HLA matching for other organs was not as clearcut as with kidneys. Hence, the matching criteria for these organs included blood type, body mass index (BMI) and clinical urgency, rather than HLA type as a primary criterion. Clinical urgency was a major factor, but it was not easy to express its degree in numbers. Exponential growth Cyclosporine led to superior graft survival in most transplants, especially kidneys, and also appeared to make the outcome of a transplant less dependent on a close HLA match. This proved to be the case for kidneys, which resulted in a huge rise in the number of kidney patients being registered on Eurotransplant s waiting list from 1980 onwards. In the course of two decades, the waiting list for kidney patients would grow from about 3,000 to over 12,000 in This was the In the early 1980s it was found that the use of the immunosuppressive compound Cyclosporin A yielded a substantial increase in the proportion of functioning grafts. Results of a cooperative international study led by Gerhard Opelz (the CTS study at Heidelberg) showed that Cyclosporin A was superior to other conventional immunosuppressive medications. These encouraging results led to re-evaluation of the prevailing procedures and need to establish HLA compatibility and other factors. In his foreword to the 1984 Annual Report, ET Director Cohen said: The impact of Cyclosporin A on graft survival was probably the single, most important and most discussed factor in the field of renal transplantation this year. Several centers reported a one-year cadaveric graft survival in excess of 90%, which would have been unbelievable only a few years ago. A disturbing trend however, is that some centers decreased the exchange of kidneys, for fear of prolonging cold ischaemia time, and thereby jeopardizing the effectiveness of Cyclosporin A therapy. price of success, as longer waiting lists and waiting times increased the logistical burden on Eurotransplant. In fact, this downside had an unexpected advantage too. The huge rise in the number of newly registered patients on the waiting list meant that sufficient funding now became available to computerise, decentralise and optimise the database, and especially the waiting list management system. As organ transplantation became a routine procedure, a new job developed in donor hospitals and transplant centers, that of transplant coordinator. Transplant coordinators (TCs) first appeared in the US in the 1970s and were typically dialysis technicians and nurses who were already working in transplant units. As the demand for transplants grew, the responsibilities of TCs expanded and they were appointed in a fulltime capacity to concentrate on the elaborate donation and procurement process, as well as community and professional education. The Acceptable Mismatch programme In the second half of the 1980s, Eurotransplant was to start a programme that would turn out to be a major advance for patients who are highly sensitised against foreign tissue antigens, and for whom it was difficult to find a suitable donor. They would often have to remain on the waiting list for a long time. This problem was addressed by the Acceptable Mismatch programme, which started in Unlike the regular renal transplant allocation process, in which the histocompatibility parameters consist of the degree of compatibility with the patient's HLA type and the absence of unacceptable antigens, the Acceptable Mismatch programme is based on compatibility of the possible donor with the combination of the patient s HLA type and the acceptable antigens present. These acceptable antigens are defined as HLA antigens to which the patient never has made any antibodies. This strategy aims to predict a negative crossmatch, which means that the risk of a rejection of the organ is diminished. To define acceptable antigens, a panel of sera developed with the help of blood bank samples is used to select donors with only one HLA-A or HLA-B mismatch with the patient. Negative crossmatch reactions imply that this particular antigen mismatch is acceptable. Twenty-five years of the Acceptable Mismatch programme have now resulted in more than 1,000 renal transplants in patients who would otherwise have had a minimal chance of receiving a donor organ. Bio Implant Services (BIS) Eurotransplant s core business from the start was the recovery and allocation of deceaseddonor organs. Early on, however, its activities were extended to other kinds of transplants, including human tissues. In 1980 collaboration began with the Department of Ophthalmology HISTORY 91

12 HOW ET WAS FINANCED IN THE EARLY DAYS After the launch of its activities in 1967, Eurotransplant was financed mainly by grants from the Dutch Ministry of Public Health, the Dutch Kidney Foundation, and the Dutch Fundraising Organisation for Health Care (total grants of Dfl. 99,000 in 1969). In 1970 negotiations started with the Dutch organisations for public and private health insurance, to obtain compensation for the tissue typing activities performed. Pending these negotiations, bills were sent to patients in the Netherlands and Germany. In March 1971 a contract was signed between ET and the Dutch public insurance companies. ET was to receive a lump sum for each new Dutch patient entering the waiting list of Dfl This amount covered the cost of a full HLA typing procedure, based on 8.7 typings per registered patient, including 1.7 donor typings. The lump sum would also cover ET s overhead cost (personnel, computers and communication). The German Krankenkassen followed this arrangement by agreeing to reimburse DM 300 typing costs for each newly registered patient. This amount also included the cost of 1.7 donor typings per registered patient. In 1972 the Dutch and German insurance companies agreed that the costs of organ transport would be charged to the recipient s health insurance company. It was agreed that in the following years the cost per newly registered patient would be recalculated yearly. In 1975 an agreement was also reached with the Dutch health insurance companies for the reimbursement of donor nephrectomy (Dfl. 1,835 charged per transplanted patient), and negotiations started with insurance companies in other ET countries. By 1975 Eurotransplant acted as a financial clearing house for the total costs of mediating organ transplants: a lump sum of Dfl. 3,116 was charged to the patient s health insurance upon registration. From this amount regional tissue typing laboratories and donor hospitals were to be reimbursed, with organ transport costs charged in addition. The Eurotransplant budget consists of a basic part for the regular Eurotransplant costs and a country-specific part for country-specific services. The budget is divided over, and financed by, the health insurers of national transplant organisations of the different member states and collected via a registration fee. The current budget, including project costs for the renewal of the core IT-system (project CORE), amounts to about 9.5 million Euros. of the Leiden University Hospital: the Eurotransplant Cornea Project. Keratoplasties were performed with matched vascularised corneal grafts, provided by ET. This led to the establishment of a cornea bank that also rendered services to ophthalmology departments in the UK, Denmark, Finland, Belgium, Austria and Germany. In 1989 the directors Bernard Cohen and Guido Persijn took the initiative to establish the Bio Implant Services foundation (BIS), to serve as mediator for the donation of heart valves, skin, corneas and bone tissue. Jon van Rood became its first chairman. It acted as interface between the donor hospital, tissue bank and tissue recipient. It was housed under the same roof as Eurotransplant but later moved, became independent and was renamed BisLife Foundation, a Multi Tissue Center mediating in tissue transplantation. It also manages its own bone bank. MODERN TIMES The history of Eurotransplant mirrors the developments in communication technology: from phone, to telex, to main computers, to personal computers and the internet. Time and again Eurotransplant had to reset standards to make ICT fit the needs of international cooperation THE 1980s SAW another development that was to become highly important for the nature of Eurotransplant s work in the 1990s. The ever increasing workload made it necessary to further computerise their operations. Managing Director Bernard Cohen was the driving force ensuring that high priority was given to computerised data management. The PIONEER computerisation project was launched in 1985 and completed in It had a slow start, a phenomenon that was, and still is, not unusual in projects involving information technology. Pioneering with computers The first major step involved merging what were then two separate activities. The analytical work had so far been performed on a computer system completely separate from the system that was used to electronically register patients on the waiting list and for recipient matching. The PIONEER project was intended to provide a unified data system that would serve all of Eurotransplant s computing needs. A crucial element would be the interaction between the central system located at Eurotransplant and computers (personal computers) in the transplant and tissue typing units. The ET user centers were to be more closely involved with, and have control over, their own data within the ET international database. Direct involvement with the processes of recipient selection and matching was now possible. The central system became operational in May It replaced the original Leiden University Hospital Information System (ZIS). From then on, the system distributed a monthly report (the actual central waiting list) and the associated local center waiting list reports. A system of regular serologic screenings and labelling was implemented. The output from this part of the system was distributed to the local centers for use and further processing. The HELLP (heart, liver, lung, pancreas) data and its subsequent processing work which had previously been done on a standalone PC system were integrated with and made operational on the central system. In 1989 Eurotransplant took over the 92 EUROTRANSPLANT

13 Another milestone reached: ET's director Henk Schippers and Jon van Rood project management, while a computer consultancy firm provided staff from its technical development department to assist Eurotransplant in Leiden with the completion of the PIONEER project. The brief life of PIONEER After a decade, around the mid-1990s, PIONEER reached the end of its life cycle and was to be replaced by the Eurotransplant Network Information System, or ENIS. This was the working title of the project to renew Eurotransplant s central computer system. The planned date for ENIS to become operational was March ENIS phase l was completed in 1995, and involved a oneto-one functional replacement of the previous system. The main consequence for the users would be that the new system was much faster, while the procedures remained stable as before. More important for the PC users was ENIS phase 2, which concerned the local systems in the various centers. By 1998, ET s Information Department had succeeded in clearing the backlog in system development and then introduced a release policy for ENIS, marking two major achievements for the department. New software was installed to improve communication with remote users. The newly installed Winframe server software facilitated remote access to ENIS at Leiden through a client-friendly graphical user interface. Remote centers could use the connection to download reports and obtain software updates. And future users would be able to download data extracts from the central ENIS database. All remote centers were updated by sending them a floppy disk or CD-ROM with the new software, together with an installation guide. In fact, however, the arrival of the Internet would soon render floppy disks and CD-ROM drives obsolete. Some of the younger healthcare professionals working with the Eurotransplant applications have probably never used a floppy disk in their entire lives. Silver jubilee Eurotransplant celebrated its 25th anniversary in Not only was the anniversary itself a joyous occasion, but one year earlier, the organisation had welcomed the dialysis and transplant centers in former Eastern Germany (DDR) as new participants. Although communicating with them was difficult at first because of the unreliable phone lines, the situation soon improved. Germany had already been ET s largest member state, and now the reunification made the country even more important. In 1995, however, dark clouds briefly seemed to gather around Eurotransplant. As was described in a previous chapter, the Board of the Leiden University Medical Center had decided to rid itself of the many foundations that had developed as spin-offs from the university hospital and were still housed on its premises. However, Eurotransplant found new accommodation after its banishment from the LUMC, and in fact this breathed new life into the organisation (see also chapter 1). While lodging with the LUMC, ET had been subject to highly restrictive regulations, and its offices had become far too small for this ever-growing organisation. At the new premises on Plesmanlaan in Leiden, ET was able to control all aspects of its operations itself, like the procurement of goods and services, and staff was no longer subject to government employment rules. The next few years were characterised by member states joining forces to streamline administrative procedures. Belgium had already introduced a transplant act in 1987 (which was amended later), and Germany and the Netherlands now also developed legislation to regulate transplantation. The body formally responsible for organ mediation in the Netherlands now became the Dutch Transplant Foundation (NTS), which contracted out this task to Eurotransplant. Belgian law also stipulates that mediation for organ transplants had to go via Eurotransplant. And in 1999, ET s cooperation with the German Bundesärztekammer, the Spitzenverband der Kranken-kassen and the Deutschen Krankenhausgesellschaft was formalised in a contract, making Eurotransplant the official mediator for all organ transplants in Germany. Regular scientific meetings and social events with all those involved also created a Eurotransplant team spirit. Government support: The Joint Declaration of 2000 During the 1990s Eurotransplant redefined its mission statement and goals, emphasising the promotion, support and coordination of organ transplantation in the broadest terms. To improve cooperation between ET member states until then wholly voluntary and enhance the commitment of the governments and health authorities of these countries, ET took the initiative to design a framework for cooperation in international allocation, to be signed by the six Ministers of Health of the ET countries (now also including Slovenia). HISTORY 93

14 This Joint Declaration of November 2000 contained the following key messages and proposals: The importance of international cooperation in organ transplantation within the ETI framework has been demonstrated and should be continued. The time is ripe to shape government involvement, also given the background of a possible broadening in cooperation within the ETI framework. There should be an objective allocation system according to medical criteria. All post-mortal organs that become available in the participating countries are to be reported to ETI. ETI s task is to ensure optimum allocation of these organs. Allocation should maximise equality of opportunity for patients; it must be patientoriented, and procedures should be transparent and objective. Government involvement is dependent on ETI s answerability to governments in the participating countries, and will be periodically evaluated. An action plan will direct the implementation of these aims. The Joint Declaration was a true landmark in the history of Eurotransplant at the turn of the new millennium - and still remains one today. The 40-year Celebration and reaffirmation of the Joint Declaration In 2007, Eurotransplant celebrated its 40th birthday. On this occasion, another joint meeting of the ET Board and the Health Ministers of the now seven ET countries was organised. The Dutch Minister, Dr. Klink, co-hosted a roundtable conference in Château St. Gerlach in Valkenburg (near Maastricht) on 24 September Topics were the development of common strategies to improve donation rates, support of donor procurement and optimisation of the use of available organs and tissues by providing a transparent and objective selection system, implementing a well-functioning quality assurance system, and assessing outcomes by an international data registry. At the closing of the conference, emphasising the continuing success of ET and welcoming the new membership of Croatia, the Ministers signed a document reaffirming the Joint Declaration from the year In this document the ministers expressed their recognition of the activities performed by ETI, and stated that the aims and plans addressed in the 2000 Joint Declaration still had undiminished validity. This successful outcome was celebrated with a dinner banquet in Aachen, courtesy of the German Minister of Health, Mrs Schmidt. Birth of the Eurotransplant Council During the roundtable conference in Valkenburg, it was decided to create an information exchange platform that would enable ET countries to benefit from mutual experiences and best practices. The first meeting of this platform took place in June Chaired by the ETI president, representatives of the respective ministries of each ET country, board members representing the national transplant societies and the Eurotransplant directors participated. Altogether three meetings of this kind were held. These discussions also revealed that the national authorities (in particular the National Competent Authorities NCAs) were looking for better inside information on ET s functioning, decision-making process, and production of regulations. A proposal was launched to change the information exchange platform into a Council where ET Board representatives would meet the competent authorities on a regular basis. The first Council meeting took place on 17 September The Council by now has been officially included in ET s Articles of Association. It has proven to be an excellent forum to inform competent authorities about the ins and outs of decisions and developments in Eurotransplant, also giving them the opportunity to bring forward their own issues. Currently, the Council plays a major role in the discussions and decisions regarding a new strategy plan, including a new governance structure for Eurotransplant. Relations with the European Union In recent years, Eurotransplant has strengthend its contacts with the European Commission, and in particular with the Commissioner for Health and Consumer Protection. There have been discussions on several occasions with the Commissioner concerning EU cooperation with organ exchange, including a site visit to the Eurotransplant offices. The 40-year Celebration and reaffirmation of the Joint Declaration at Château St. Gerlach in Valkenburg 94 EUROTRANSPLANT

15 EUROTRANSPLANT S SCIENTIFIC OUTPUT Eurotransplant s task is not merely the matching of recipients and donors but it aspires to be a true partner in the future of medicine. Its actions and procedures are well justified in robust scientific publications, and are stepping stones in providing care to ever more patients EUROTRANSPLANT S original scientific basis was the finding that the acceptance of a transplanted donor organ by the recipient s body depends on the degree of HLA match between the two. The more foreign antigens a donor organ has compared to the recipient, the more likely it is that it will be rejected. These antigens were originally identified with the help of antisera. The basis for HLA typing was formed by sera obtained from pregnant women who had produced antibodies against the HLA antigens that their foetus had inherited from its father (as 1976 J.P. van Hooff, The relative importance of HLA matching in kidney transplantation 1985 G.G. Persijn, HLA-matching and blood transfusion(s) in renal transplantation 1989 G.F.J. Hendriks, HLA-DRw6: A marker for immune responsiveness in renal transplantation 1991 A.F. Groenewoud, Determinants of renal allograft function and survival 1992 J. Thorogood, Statistical modeling of renal allograft survival and associated prognostic factors Jon van Rood had proved in his 1962 PhD thesis). The immunohaematologists (experts on the immunology of the blood) at the Leiden Blood Bank were able to analyse these sera in detail, and select the most useful ones, which then became the standard reagents for HLA typing. These laboratory findings were then made suitable for application in the clinic (for the actual transplantation), a process that nowadays is called translational medicine : applying basic scientific knowledge in clinical practice. Such processes always involve some degree of trial and error. An important requirement is that results of research need to be published in scientific journals, to enable other scientists ( peers ) to evaluate the scientific facts. For half a century now, scientists and clinicians affiliated with Eurotransplant have been publishing articles in so-called peer-reviewed journals. They have also written PhD theses, and have cooperated in high-quality research projects, so-called randomised clinical trials (RCTs). In some of these trials, Eurotransplant took the role of clinical research organisation (CRO) leading the trial. This chapter briefly summarises this huge research effort. Matching: sowing the seeds for new generations Eurotransplant earned the status of center of excellence for histocompatibility testing via its Reference Laboratory by publishing cutting-edge research about HLA and typing. Soon after Eurotransplant had been founded in 1967, it started to publish articles on the principle of matching as a tool to enhance graft and patient survival. One of the first articles from Leiden on the value of HLA matching for successful transplantation, published in the renowned medical journal The Lancet, was written by nephrologist Hans van Hooff and co-workers in Van Hooff s PhD thesis appeared in 1976, and discussed the topic in greater detail. This became the start of a whole series of theses and publications on the effect of immunological characterisation of donor organs and patients on survival rates. Some of the theses are mentioned left, as they represent the beginning and continuity of the scientific work and interests of Eurotransplant and its community. An important review article by ET staff on the effect of HLA matching on the survival of both kidney transplants and their recipients was published in the prestigious New England Journal of Medicine in In the course of the 1970s and 80s, HLA matching became more and more sophisticated, partly because HLA antigens could be characterised ever more accurately, but also because a new type of HLA antigens (belonging to the Class II molecules of the Major Histocompatibility Complex) was discovered at Leiden: HLA-DR. This type of HLA antigen is not expressed on all cells. A new method to distinguish different cell populations at the same time, using twocolour fluorescence, 3 proved crucial for the typing of these antigens. Afterwards, the process of typing HLA with antisera was gradually replaced by molecular typing techniques based on DNA analysis. The value of these more reliable molecular techniques in matching donor organs and patients was demonstrated and published in a 1991 study by Gerhard Opelz and co-workers. 4 Eurotransplant staff regularly published the excellent results achieved by the successful innovative matching strategy of the Acceptable Mismatch (AM) programme, specially developed to benefit the transplantation of organs into highly sensitised patients, by having their acceptable antigens predefined. The purpose of these publications was to stimulate other organisations to take action for this group of patients, as without this strategy these patients would have to remain on the waiting list for years. 5 In the early years of Eurotransplant, the allocation of kidneys was purely based on HLA matching, HISTORY 95

16 which meant that highly sensitised patients or those with rare HLA phenotypes had to wait for years, with very little chance of a matching donor kidney. In 1996, new insights into optimal allocation methods led to the more balanced ET Kidney Allocation System (ETKAS), which also took other parameters, including waiting time, into consideration to determine a patient s place on the waiting list for receiving a donor kidney. This system was also published, both to make others aware of the new insights and to get critical feedback from peers. 6 The various forms of allocation were evaluated at Eurotransplant, resulting in a hierarchical system. When matching kidney donors and recipients in the ET region, first high-urgency patients or patients on the Acceptable Mismatch list are scanned, followed by patients with zer0 mismatches regarding the A, B and DR types of the HLA system (so-called identical or fullhouse match), and then finally the regular HLA-based Kidney Allocation System is applied. 7 Another ongoing research project about which Eurotransplant staff has published articles was the observation that HLA-DR matching helps to prevent that a patient produces new HLA antibodies after the transplant has been rejected. 8 More patients and beyond The arrival of cyclosporine led on the one hand to an increase in the number of kidney patients on the waiting list, and on the other hand to new lists for patients waiting for other organs. This prompted Eurotransplant to develop a new statistical method to analyse the risk profile of patients on the waiting list, a method that has since become standard practice worldwide. 9 Keeping track of waiting-list patients is a complex process. Patients may die before having received a transplant, or they can be removed from the list due to deteriorating health or to improvement of their clinical status. If these aspects are not duly considered, mortality rates of those on the list could be overestimated. In order to judge whether a specific allocation rule, for instance a specific blood group rule, functions well, it is essential to get the outcome metrically correct. Metric characterisation of patients on the waiting list allows patient populations to be statistically analysed and the data processed. These analyses are published, and the data on which they are based is made accessible on the Eurotransplant website in userfriendly format: the Online Statistics Library. The doctors treating a particular patient have access to a closed member section using a special user ID and password, where they can find more information and statistical data about the probability of a suitable donor organ becoming available for a specific patient within a certain period of time. After a recipient has undergone transplantation, Eurotransplant stays in touch with the transplant center to keep track of the outcome. Analysis of this data may help detect factors which influence transplantation results in the longer term. Finding such indicators could then lead to modification of the allocation criteria in matching procedures used to select the most suitable recipients. Among these factors are the various tissue characteristics, the organ preservation techniques used, the age of donor and recipient, and the use of immunosuppressive agents to prevent rejection. Attempts to optimise the allocation process are often based on creating special categories of patients. In its early days Eurotransplant had already introduced the European Immunized File for long-waiting patients with a high load of cytotoxic antibodies ( 85% Panel Reactive Antibodies). A more recent example is the process of allocating donor hearts to children (paediatric patients), for which the paediatric High Urgency (HU) heart allocation scheme was started in Such programmes continue to be developed further: the status of regular Urgency (U) was then additionally defined in And in 2011 Smits and co-workers published a review article on how to define a child s status for heart transplantation. 10 Eurotransplant provides major contributions to these kind of debates. Another special category has been introduced in 1999 for patients on the kidney waiting list and donors aged 65 years and older (Eurotransplant Senior Program), based on the concept of matching between metabolic demands of the graft recipient and the excretory capacity of the donor organ. Smits and co-workers published the first experiences with excellent results in the American Journal of Transplantation. 11 Since 2001 this allocation has been incorporated into the regular allocation scheme. Randomised clinical trials (RCTs): enhancing the donor landscape The 21st century saw a major new development in the matching procedures described above, as greater attention was given to optimising the donor organ itself. Specifically, researchers studied the effect that the type of organ preservation solution had on the outcomes of kidney transplants. An early predecessor of these studies was the research done at Eurotransplant in the 1970s into the preservation solutions that were being used in practice. It was concluded that there was no common standard; in fact each Eurotransplant publishes scientific literature, adding to the global knowledge on many aspect of transplantation 96 EUROTRANSPLANT

17 local center used simply what they considered suitable. Elimination of additives that proved not to be essential led to a standard formula which was called the Eurocollins Solution, and which functioned well for a long time. In the meantime other solutions were tested and made available. More recently, a large-scale randomised clinical trial (RCT) compared the HTK formula (Custodiol ) with the UW (University of Wisconsin) and Eurocollins solutions. 12 Another aspect that was studied in an RCT was the effect of different organ preservation methods on renal transplant outcomes. On behalf of leading transplant centers in the Netherlands, Germany and Belgium, the Scientific Steering Committee for this trial, together with Eurotransplant, announced in October 2005 the start of the Machine Perfusion Trial. This was the first large, prospective multicenter trial to investigate the relative efficacy and cost-effectiveness of continuous hypothermic machine perfusion versus the prevailing alternative of preserving kidneys in static cold storage until transplantation. The short- and longterm findings were published in a leading medical journal See, for instance, H.A. Erlich, G. Opelz and J. Hansen, HLA DNA typing and transplantation, Immunity 14 (2001), S. Heidt, M. Witvliet, G.W. Haasnoot and F.H.J. Claas, The 25th anniversary of the Eurotransplant Acceptable Mismatch program for highly sensitized patients, Transplant Immunology 33 (2015), J. de Meester, G.G. Persijn, T. Wujciak, G. Opelz and Y. Vanrenterghem, The new Eurotransplant Kidney Allocation System: report one year after implementation, Transplantation 66 (1998), F.H.J. Claas, A. Rahmel and I.I.N. Doxiadis, Enhanced kidney allocation to highly sensitized patients by the Acceptable Mismatch Program, Transplantation 88 (2009), I.I.N. Doxiadis, A. Rahmel and F.H.J. Claas, Towards kidney allocation on basis of HLA-DR compatibility, Clinical Transplants (2010), J.M.A. Smits, H.C. van Houwelingen, J. De Meester, G.G. Persijn and F.H.J. Claas, Analysis of the renal transplant waiting list: Application of a parametric competing risk model, Transplantation 66 (1998), the gap between supply and demand for donor organs. Eurotransplant decided to tackle the problem of the growing organ shortage and thus became the driving force behind the development of EDHEP - the European Donor Hospital Education Programme. In 1991, with the generous support of J. De Boer, J. De Meester, et al., Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Eurocollins, Transplantant International 12 (1999), J.J. van Rood, A. van Leeuwen en J. S. Ploem, Simultaneous detection of two cell populations by two-colour BY 1990, EUROTRANSPLANT was providing its services to the Netherlands, Germany, Austria, Belgium and Luxembourg, covering a population of over 116 million people. In that same year, however, the ET region experienced a general fall in organ donation rates, which resulted in a further increase of During half a century of Euro transplant, the demand for donor organs has only increased. Special education programmes were created to help make doctors and nurses feel more effective in dealing with bereaved families and when requesting consent for donation J.M. Smits, J. Thul, et al., Pediatric heart allocation and transplantation in Eurotransplant, Transplant International (2014), 1-9. J. De Boer, J. De Meester, et al., Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Eurocollins, Transplantant International 12 (1999), G.G. Persijn, B. Cohen, et al., Effect of HLA-A and HLA-B matching on survival of grafts and recipients after renal transplantation, New England Journal of Medicine 307 (1982), DONATION THE WEAKEST LINK 10 J.P. van Hooff, G.J. van der Steen, H.M. Schippers and J.J. van Rood, Efficacy of HL-A matching in Eurotransplant, The Lancet ii 2(7792) (1972), The European Donor Hospital Education Programme (EDHEP) in 1995 fluorescence and application to the recognition of B-cell determinants, Nature 262 (1976), C. Moers, J.M. Smits, et al., Machine perfusion or cold storage in deceased-donor kidney transplantation, New England Journal of Medicine 360 (2009), 7-19; C. Moers, J. Pirenne, et al., Machine perfusion or cold storage in deceased-donor kidney transplantation, New England Journal of Medicine 366 (2012), HISTORY 97

18 the Dutch Kidney and Heart Foundations, Eurotrans-plant developed a professional donation education programme for the Netherlands. Later, Sandoz Pharma in Basel, Switzerland, also agreed to support the initiative and EDHEP became an international educational tool to help increase donation. The programme was part of a multifaceted approach to close the gap between the supply and demand for organs and tissues for transplantation. It was created to meet the widely perceived need to help doctors and nurses become more effective in dealing with the bereaved family and in requesting organ donation. EDHEP was developed and delivered by professionals from different specialties including medical doctors and clinical psychologists from the University of Maastricht, transplant coordinators (TCs) and communication specialists. The first part of EDHEP was called Meeting the Donor Shortage. Its aim was to raise awareness and understanding of organ and tissue donation and transplantation among all levels of medical, nursing and assisting staff in all hospital departments. The second part was named The Grief Response and Donation Request. It took the form of a highly interactive one-day awareness skills workshop, organised and introduced by the local transplantation coordinators and moderated by communication skills experts. The workshop targeted professional staff working in any area of medicine that brings them into contact with bereaved relatives. It aimed to help participants improve their communication skills and heighten their sensitivity to the needs of the bereaved. Professionals operating in countries with either a presumed consent or an opting-in donation system found the major elements of the EDHEP workshop very relevant. Communication skills are crucial when informing a bereaved family about the option of organ donation and the possibilities to donate different organs. EDHEP strengthened by Donor Action The scope of the EDHEP approach was widened when Eurotransplant International Foundation started to cooperate with Spanish and American organisations, in order to pool their expertise to help hospitals increase their donation rates through improved donation practices. The resulting Donor Action (DA) programme took a systematic approach towards achieving quality assurance in donation. The five DA programme modules formed the Critical Donation Pathway. The modules provided concepts and examples of adaptive and stimulatory measures that correspond to the critical steps in the donation process and come as a tool kit for daily use in ICUs. The modules were to be used alone or in any combination according to identified specific needs. The data from DA pilot hospitals showed that ICUs differed in their starting points and needs. The pilot data identified a significant number of unused potential donors (whose donation could not be effectuated) and also suggested that there may be important differences in attitudes, perceived skills and levels of confidence in professionals across countries. There was a growing awareness that further efforts to increase the organ supply had to rely on the interplay between legislation (opting-in/ opting-out), living donation (related and unrelated), and deceased-donor donation (heartbeating/non-heart-beating). The young and the critically ill The decrease in the number of fatal traffic accidents and improvements in intensive-care facilities in many countries contributed to a fall in the number of deaths among younger people, and consequently to a decline in the number of high-quality organs available for transplant. Most allocation algorithms give priority to the very young and clinically high-urgency patients. Such issues demonstrate the tension between the desire of the medical profession to provide the best possible care for each individual patient in a fair manner (a dutyof-care based approach), and the desire to provide the greatest good to the greatest number of people (a utilitarian approach). The characteristics of patients on the waiting lists differ for the various organs. Thus transplanting a kidney from a There has always been a shortage of donor organs, both in the past and nowadays. Many recipients are so thankful for their gift that they take part in (sports) activities to promote organ donation, such as Etienne Bischops from Luxembourg, in the "Relais pour La Vie (Relay for Life) 98 EUROTRANSPLANT

19 patient s living relative may provide an alternative to having to wait a long time for a suitable deceased-donor kidney. However, such donations are ethically acceptable only if both the recipient and the donor are well informed and have voluntarily made a decision. This escape route does not exist for organs like hearts (with livers and lungs occupying an in-between position). Nevertheless, allocation of donor hearts raises ethical problems too. Here, the question arises as to who should receive the available organ: the patient who has been waiting the longest, the patient who has the best chance of success, or the patient with the most urgent need? Difficult questions like these were and still are the order of the day. But what about the elderly? Within Eurotransplant, these observations suggested a new initiative in which organs from older donors could be used more effectively. The Eurotransplant Senior Program (ESP) or Old for Old programme seeks a logical response to the universal trend of further extending the donor criteria. This programme had its pilot study around the turn of the millennium, with the aim of achieving, firstly, a more efficient use of kidneys retrieved from elderly donors, and secondly, the possibility to offer transplantation more often to older patients. Selection criteria in the programme were: organs from older donors (65 years and over) going to older recipients (65 and over); first transplants only; only recipients who are non-sensitised at the time of matching. The rationale behind the recipient age limit was that a kidney graft that outlives the recipient is considered a success. If donor organs are physiologically slightly sub-optimal as is more likely with older donors the graft has a greater chance of outliving an older than a younger recipient. In addition, a prerequisite of the study was to reduce the cold ischaemia time as much as possible to maximise the outcome in these recipients. These initiatives to increase donor pools by education and training (EDHEP and DA), and to make more efficient use of the immunological and physiological characteristics of donor organs (Acceptable Mismatch and Old for Old) are all spin-off products of Eurotransplant International and its dedication to close the unacceptable gap between donor organs and recipients. In conclusion, these new programmes to some extent represent a break with the past. It is not merely a matter of as many donors and as many transplantations as possible. New developments in Eurotransplant s allocation system also aim to reduce mortality rates among those on the waiting list, to utilise less-thanperfect organs and to prevent that organs that have been removed are not used (minimising the discard rate ). MATTERS OF LIFE AND DEATH The kidney allocation system became more and more sophisticated and was extended to other solid organs. Since the 1980s Eurotransplant has allocated donor livers, hearts, and pancreas. Thereafter, the allocation also included lungs and intestines EUROTRANSPLANT was founded in 1967 to ensure that the recent breakthroughs in organ transplantation techniques would benefit patients with kidney failure. Jon van Rood saw the opportunity to create a valuable database of kidney patients in close cooperation with dialysis and transplant centers in the Netherlands, Belgium, Luxembourg, Austria, West-Germany and also Switzerland. Quite an achievement in view of the different procedures, legislation and languages used in these countries. Van Rood came up with the name Eurotransplant, indicating his intention to expand the organisation to include more countries. Pioneers of transplantation medicine such as Yves Vanrenterghem (Leuven), Rudolf Pichlmayr (Hanover) and Raimund Margreiter (Innsbruck) would for many years hold key positions in an organisation that survived more on goodwill than on political support from the member states. Expansion was slow but steady, with countries like Croatia, Slovenia and Hungary now also participating in Eurotransplant. Thus, ET became a truly transnational European organisation, without having received formal backing by the European Union. The figure on the following page illustrates the huge improvements that have been achieved. It shows how the percentage of donor kidneys surviving over a period of three years after the transplant has increased from about 50% in the period to almost 90% in the period. What the figures in the graph also show is the exponential growth in the numbers of transplanted kidneys, to an average of 3,400 a year. Although immunosuppressive drugs like cyclosporine nowadays effectively prevent the rejection of transplanted organs, a good HLA match still offers major benefits to patients. Landmark ETKAS: the Eurotransplant Kidney Allocation System The allocation of deceased donor organs is Eurotransplant s core busi- HISTORY 99

20 ness, and the allocation process is continually being adjusted. A new kidney allocation system was introduced in 1996: the Eurotransplant Kidney Allocation System or ETKAS. The new ETKAS protocol was based on a proposal by Thomas Wujciak and Gerhard Opelz. The originally proposed procedure applied the following five criteria: mismatch grade, waiting time, mismatch probability (a correction factor increasing the selection chances for patients with uncommon HLA phenotypes and of homozygous or sensitised patients), local transplants and import/ export balance. Points were given to each allocation criterion, and the total point score was computed by entering each factor into the formula. Computer simulations had ETKAS (1996): Transparent points system based on more factors than HLA matching only MIN MAX HLA-A, B, DR mismatch Mismatch probability Waiting time 0.09 points per day Distance of donor to transplant center National import/export balance shown that this allocation procedure decreased the average and maximum waiting times of patients, adjusting for rare HLA phenotypes, without leading to an unacceptable decrease in best achievable HLA matches or to large kidney exchange imbalances. Especially, as it was supported by experimental (albeit retrospective) data, the proposal was accepted by the entire Eurotransplant community. It promised to provide a better alternative, avoiding the flaws of the previous allocation procedures. One of the improvements that the new procedure undoubtedly has brought about is a decrease in the waiting time for more difficult to mediate categories of patients. Liver: towards the MELDbased allocation policy The number of patients on the waiting list for a donor liver has steadily grown over the years. Just as matching criteria for kidneys were adjusted in the course of time, liver allocation also saw a gradual development. In the early years, liver allocation was first of all patientoriented, based on the situation in each donor center. If a suitable recipient was available at the donor center, the liver could be transplanted at this same center. If no suitable recipient was available, the liver was allocated to a patient at a different center, based on urgency and waiting time. In 1996, a more center-o riented liver allocation system was introduced. When a donor liver became available, it was offered to a specific center, and this center could select the most suitable patient on its own list. This was done using a so-called ROTA list, on which the centers were ranked on aspects like the size of their transplantation programme and the most recently accepted liver. By the year 2000, the so-called Child-Turcotte-Pugh liver score (CTP score) was adopted for allocation, besides the waiting time criterion. This score represented the level of urgency for a transplantation: the poorer the medical condition of a patient on the waiting list, the higher the score, and thus the higher the chances of being allocated the available organ. Despite the use of the score, the growing number of deaths on the liver waiting list (due to scarcity of organs) made it necessary to think about another allocation system. This was found in the so called MELD score, a liver allocation system that has been in use within Eurotransplant since MELD stands for Model for End- Stage Liver Disease and was initially developed in the U.S. to predict the survival of patients with liver cirrhosis. The MELD score is based on the risk of dying within three months, and on objective and widely available variables. After careful evaluation within the Eurotransplant population, the score was implemented after approval by the authorities willing to accept this system. A patient s score is regularly recalculated on the basis of their actual condition. The higher the score, the more Factors used in the ETKAS computer program, showing that apart from tissue typing data other factors also play a major role in allocation. The beneficial effect of HLA matching on kidney graft survival still exists with current immunosuppressive treatment. 100 EUROTRANSPLANT

21 urgent the transplantation. The new system actually has led to a decrease in waiting list mortality, but has also revealed that the patients with the greatest need for a transplant have a lower overall survival rate after transplantation. This makes it very clear that even a new system has to be continuously evaluated and adjusted to make the best possible match, which also means the longest possible survival after transplantation. Pancreas allocation systems The first pancreas transplantation within Eurotransplant occurred in In the early years, pancreas allocation was also patient-oriented, based on individual donor centers. Just as with livers, if a suitable recipient was available at the donor center, the pancreas could be transplanted at this same center. In case no suitable recipient was available, the pancreas was allocated to a patient at a different center, based on urgency and waiting time. In 2003 a new allocation system was adopted, based on national priority. In the EPAS, the Eurotransplant Pancreas Allocation System, allocation is based on the principle that allocation at the national level has priority over the international level: if a suitable recipient is available in the country of the donor, the pancreas can be transplanted in the donor country. The patient list is drafted using criteria of urgency, waiting time and blood type. In the 1980s, pancreas allocation was extended to include pancreatic islets allocation, which was based on an age-dependent criterion. If the pancreas donor was older than 50 years, only islets would be offered. If the donor was younger than 50 years, transplantation of the solid organ was preferred over that of islets. Thoracic (heart & lung combined) allocation system The first heart transplant within Eurotransplant was in Just as with liver and pancreas transplants, allocation was initially patient-oriented, based on donor center. The heart was transplanted to a recipient in the donor center, if a suitable patient was available there. If not, the heart was allocated to a patient in another center, based on urgency and waiting time. The year 2000 saw the adoption of the Eurotransplant Thoracic Allocation System (EThAS), an allocation system for the transplantation of hearts and lungs or combined heart/lung transplants. This was also a patientoriented allocation and based on urgency and waiting time. In recent years a growing discrepancy has arisen between the number of patients on the heart waiting list and the number of available donor hearts/ lungs, due to decreasing donor numbers. This has resulted in a declining transplantation rate and to a situation in which the vast majority of transplant recipients were in a very critical condition. The existing heart allocation system prioritizes on medical urgency and waiting time, not taking any survival probability into account. Patients can be assigned a high-urgency (HU) status if they meet certain criteria of disease severity. While the HU status was initially intended to bypass the regular waiting list in very exceptional cases and to allow the patient to get transplanted within a very short period of days or weeks, this is now no longer the exception, but the rule. Transplanting patients in a very ill condition also means that the transplant outcome worsens, which is undesirable. In 2011, Eurotransplant initiated the development of a benefit-based heart allocation system, which was named the Cardiac Allocation Score (CAS). The first results were promising, but as with every new system, it needs to be evaluated on a large cohort of patients. This work is currently in progress and is done not only within the centers of one member state, but also with centers from other member states. After all, the system should be of benefit to all patients on the heart waiting list. Lung allocation system The first lung transplant within Eurotransplant was carried out in Like the allocation systems for liver, pancreas and thoracic transplantation, the allocation of lungs was initially patientoriented, based on donor center. In 1998 a new rule was published in the U.S., stating that existing allocation policies have to meet certain conditions and have to create an equitable organ allocation system using objective medical criteria and medical urgency. This led to a new lung allocation system, the LAS, which takes the urgency of a transplant into account as well as the probability of dying while on the waiting list. This means that this model is based on the assumed benefit of lung transplantation for the patient. The LAS also worked perfectly for the Eurotransplant population and was first introduced in Germany in 2011, after approval by the national authority. It was adopted in the Netherlands in The mortality rate on the waiting list went down, but the diagnosis of the listed patients also shifted, so that it more accurately reflected the actual urgency of a transplant. Like every system, the LAS is constantly being evaluated to check whether adjustments have to be made to benefit waiting list patients. This work is ongoing.. Intestine allocation system The first intestine transplant within Eurotransplant took place in 1989, but it took quite a long time until the second could be performed, in The number of intestine transplants has remained rather small, with only five transplants within ET in The current allocation process is based on three criteria: national before international (donor country first); blood type identical before compatible; and patient waiting time. As the intestine allocation system has not been reviewed for some years now, an international consensus conference of experts from the intestine transplant centers within ET have come together to discuss an update of the intestine allocation, which is currently being developed. HISTORY 101

22 COMING OF AGE In cooperation with its partners, Eurotransplant today continues to play a pivotal role in trying to bridge an ever-increasing gap between patients on the list awaiting transplantation, and the stagnant number of post-mortem donor organs, and in its task to serve patients in eight European countries with over 135 million inhabitants. AS A RESULT of the geopolitical upheaval at the end of the 1980s, the centers in the former East Germany joined Eurotransplant in In addition, the ET management invested a great deal of effort in trying to get the transplant centers in the Czech Republic to participate in Eurotransplant as well. ET staff were sent over there to give courses on tissue typing, donor procedures, administrative guidelines and allocation policies. After everything had been arranged with the Czech dialysis and transplantation centers, however, the country pulled out at the last moment, due to a political decision. Towards an Assembly of Centers Jon van Rood took retirement in 1996, and resigned from his position as chair of the Eurotransplant Board. He was succeeded by Leuven nephrologist Yves Vanrenterghem. Van Rood had successfully presided over ET for three decades, but there was now a consensus that a turnover in ET leadership was needed. This, and the growing importance of other organs than kidneys, led to a major change in the organisational structure in This change also responded to the rising calls for more democracy in the rapidly growing organisation. LIST OF (VICE-)PRESIDENTS ( ) ETI PRESIDENTS COUNTRY / CENTER PERIOD Jon J. van Rood Netherlands / Leiden Yves Vanrenterghem Belgium / Leuven President-elect President Past-president Bruno Meiser Germany / Munich President -elect today President ETI VICE-PRESIDENTS Ferdinand Mühlbacher Austria / Vienna Xavier Rogiers Belgium / Gent 2014 today ORGAN-SPECIFIC ADVISORY COMMITTEES Organ-specific Advisory Committees evaluate rules regarding procurement, preservation, allocation and transplantation, and are advisory to the board. The following organ-specific committees exist: Kidney Advisory Committee (ETKAC) Thoracic Advisory Committee (EThAC) Liver Intestine Advisory Committee (ELIAC) Pancreas Advisory Committee (EPAC) Other Advisory Committees: Tissue Typing Advisory Committee (TTAC): advises the board on any aspect concerning tissue typing activities in Eurotransplant. Organ Process Chain Committee (OPCC): advises the board on any aspect of and formulates standards for donor management and organ procurement, and stimulates education of the medical profession. Financial Committee (FC): advises the board on any financial matters regarding the foundation. Ethics Committee (ETEC): advises the board on any ethical aspect involved in the work of Eurotransplant. Information Services Working Group (ISWG): consults and advises on strategical and tactical policies, innovations and improvements in the field of Information and IT. Scientific Registry Working Group (SRWG): sets recommendations and evaluates proposals with respect to the development of the ET Registry system Since November 1987, there had been a Eurotransplant Users Meeting. This regular gathering was transformed into an Assembly, in which each participating center (recognized as such by local/national authorities) was represented by one delegate. In centers with more than one transplant programme, one representative of each programme would be delegated to the Assembly. Although all organ programmes of each center thus had a seat, voting power was related to the number of transplants performed in the previous year. The Assembly was subdivided into organ-specific sections for kidneys, hearts and/or lungs, livers and pancreas/islets, and a section for tissue typing. The main task of the Assembly was to make proposals for adjusting ongoing allocation procedures and implementing novel procedures via scientific advisory committees supporting the board. The composition of the board was to be redefined too. In 1994, the old board was composed of 16 members, who (except for the 4 chairpersons of the National Transplant Societies) were selected by means of co-optation for a period of 4 years, with the possibility of re-election. The new board consisted of 15 members, eight of whom were chosen by and from the Assembly, while five members were appointed ex officio: the four chairpersons of the National Transplant Societies and one head of the Eurotransplant Reference 102 EUROTRANSPLANT

23 Eurotransplant s organisational structure from 1994 Laboratory. The remaining two positions in the board were filled by a financial specialist and an ethical expert, who were selected on a personal basis by the board. In those years, the number of centers for heart, lung, liver and pancreas transplantations in addition to the traditional kidney transplant centers grew quickly to several dozens (reaching a grand total of 219 programmes, including tissue typing labs in 1995). Strenghtening the ET community Organ transplants involve making quick decisions in matters of life and death, but the procedure in Eurotransplant was actually rather administrative. Hence, it became important to start team-building efforts, both at the Leiden office and internationally. Of course there was the annual Eurotransplant Meeting, which had served from the start to facilitate information exchange, but later on the managers of transplant centers in the six member states were regularly invited to come to Leiden to meet face-to-face with the people they spoke to on the phone. In addition, clinical research was stimulated from 1981 onwards by annual Winter Meetings in the Austrian town of Fügen, which started in The local host there was Raimund Margreiter a renowned surgeon and head of the Transplantation Department of the Innsbruck University Hospital (Klinik für Visceral-, Transplantations- und Thoraxchirurgie). The actual scientific meetings were interspersed by outdoor sports activities (the slalom race being particularly popular and competitive), resulting in strong personal ties. The Winter Meetings were later moved to the nearby town of Alpbach. Before joining the ET staff, Verena Diepeveen had helped to run a ski club, making her the obvious choice to take over the task of organising the Winter Meetings. This she did with great dedication and pleasure for many years. She was tirelessly supported by slalom expert Herman Fetz, transplant coordinator from Innsbruck. From 1987, ET Summer Meetings were also held, in the German city of Lübeck, organized by Jochem Hoyer from the local transplant center. EXPANSION Eurotransplant began as a small foundation under Dutch law and gradually became an internationally established non-governmental organisation (NGO); it therefore changed its name to Eurotransplant International Foundation. Its objectives were defined as: a achieving an optimal use of available donor organs and tissues; b securing a transparent and objective selection system, based upon medical criteria; c assessing the importance of factors which have the greatest influence on transplant results; d supporting donor procurement to increase the supply of donor organs and tissue; e further improving the results of transplantation through scientific research; f promoting, supporting and coordinating organ transplantation in the broadest sense. As we saw above, in the mid-1990s everything had been prepared for the accession of the Czech Republic, but this fell through at the last moment. However, other partners did join. Further professionalisation For the first 25 years of its existence, Eurotransplant could be characterised as the initiative of a small group of enthusiasts, who knew each other and had become friends through their clinical and scientific work. Co-optation was used to recruit new participants from the world of transplantation. At the organisation s 25th anniversary in 1992, Jon van Rood felt they could look back on the past with some satisfaction:... we have fulfilled our primary goal: to prolong graft, and by that patient survival, substantially. The next years saw the start of a new phase, in which the organisation became much more professional. Individual Advisory Committees were installed for each of the areas (i.e. organs) in which Eurotransplant was active, to assist the board. The aim was to establish an organisation in which... the criteria of transparency, democratic involvement of representatives from the different organ transplant programmes and nationalities would be guaranteed, in order to meet the current and future demands of the Eurotransplant Foundation in the 21st century. The year 2000 saw the start of an ambitious project by the Eurotransplant office: the development of a quality management system. This process was finalised on December 2001 by a certification audit, which resulted in the granting of the ISO 9001: 2000 certificate. This achievement was obviously the result of hard work, involving the entire office staff. The first procedures to be described and assessed were the registration and allocation procedures. As this is the core business of Eurotransplant, ample time was taken to describe these in detail. In the subsequent stages, all other procedures at Eurotransplant were formally described, including those for HISTORY 103

24 personnel recruitment and education, supply and resources. Accession of Slovenia: 2000 Slovenia was recognized as an independent state in Soon thereafter, during the second half of the 1990s, Slovenia and Eurotransplant started membership negotiations. Over the following period, the country invested great effort to fulfill all requirements for accession. This led to a formal cooperation in 1999 for high-urgency and highly sensitised patients. Establishing a close cooperation with Eurotransplant based on exchange of professional of knowledge and good personal relationships resulted in full membership on 1 January Slovenia Transplant was established in 2002, and took over the responsibility for organ donation and transplantation. The organisation was also responsible for public campaigns addressing both organ donation and transplantation, in which it involved itself with great commitment. This resulted in a constant growth of the number of donated and transplanted organs, thereby significantly improving the situation for Slovenian patients in need of organ transplantation. Slovenia has recently achieved the highest number of heart transplants amongst all Eurotransplant member states per million population. Furthermore, median waiting times for kidney transplants decreased from six or seven years in 2000 to less than two years nowadays, which is a major success for Slovenia Transplant and the Slovenian society. Slovenia, being a small country, can be very proud of its pioneering role in developing high-quality transplant programmes. Furthermore, the country is an example for other countries when it comes to public information and public awareness. The very active and innovative communication to the public by Slovenia Transplant forms an essential part of its successful efforts and achievements. Accession of Croatia: 2007 In February 2003, only a few years after gaining full sovereignty, the Republic of Croatia applied for EU membership. In April 2004, the EU Commission concluded that Croatia was a functioning democracy, with stable institutions guaranteeing the rule of law and respect for fundamental rights, and recommended that negotiations for accession to the European Union should be opened. In the autumn of 2005, the Minister of Health of Croatia Dr. Neven Ljubičić, sent a letter to the president of Eurotransplant, expressing his interest in cooperating with Eurotransplant. In November 2005, the president and the general director visited him. During that meeting, the Minister and Dr. Mirela Bušić, the coordinator for the national transplant programme, explained their wish for a multilateral agreement for high-urgency, highly immunised and paediatric patients. This was the beginning of a fruitful cooperation. In May 2006, a preliminary cooperation agreement for these patient groups was signed, and only two month later, on 20 July 2006, the first Croatian HU liver patient was registered on the Eurotransplant waiting list and was successfully transplanted on 22 July. One year later, on 26 May 2007, Croatia became the seventh full member of the Eurotransplant International Foundation six years before becoming a member of the EU. The entire ET Board joined the ceremony in Zagreb, since the occasion was combined with the regular May Board Meeting. In addition, many distinguished members of the Croatian health care community joined the event. Meanwhile, the system of organ donation and transplantation in Croatia has been further improved and professionalised. While in the first half of the last decade, the average number of donors per million On behalf of Slovenia in 1999 the contract was signed by Primož Rode, director of UMC Ljubljana at that time (left), with ET's directors Bernard Cohen and Guido Persijn 104 EUROTRANSPLANT

25 Signing ceremony of Hungary, the latest country to join Eurotransplant in 2013 inhabitants of Croatia was seven to nine, the country has in the meantime become a European champion not only regarding organ donation, with more than 35 donors per million inhabitants, but also with respect to the number of organ transplants performed. This success has prompted the world s health care community to recognise the Croatian model as a good example for other countries to follow, especially in Southeastern Europe. Accession of Hungary: 2013 In 2006, both Hungarian health politicians and professionals started initiatives to develop cooperation with Eurotransplant. In spite of several visits by Eurotransplant s president and general director to the Ministry of Health in Budapest, progress was limited because of concerns with some parties involved in transplantation in Hungary On 26 May 2007, Croatia became the seventh full member of Eurotransplant about such a cooperation. In order to overcome these worries, a meeting was organised by Dr. Langer, head of Transplantation and Surgery of the Semmelweis University, on 30 June 2010, between the Eurotransplant president, the Eurotransplant directors and Hungarian representatives of the Semmelweis University, University of Szeged, University of Pécs, the Hungarian Transplantation Society, the Ministry of Health and the National Blood Bank Institute. Based on the results of this meeting, negotiations for a preliminary membership agreement were started with the Ministry of Health. On 2 November 2011, in the presence of the Hungarian State Minister for Health, the Eurotransplant president and vice-president signed the preliminary Cooperation Agreement with Hungary, effective as of 1 January The ceremony was followed by the 20th International Semmelweis Symposium dedicated to organ transplantation. In the following months, the tissue typing lab in Budapest got its accreditation from the European Federation for Immunogenetics, and the issue of authorisation and registration of foreign doctors coming to Hungary for procuring organs was solved. In the autumn of 2011, Prof Perner, former head of the Department of Transplantation and Surgery at Semmelweis University started to negotiate the conditions for full Eurotransplant membership for Hungary. Following the successful conclusion of negotiations, the ET Board was received by the Semmelweis University in Budapest on 27 May The meeting was followed by the signing ceremony for the full membership contract between Hungary and Eurotransplant. The ceremony took place in the presence of the Hungarian Minister of National Resources Zoltán Balog and the State Minister for Health, Miklos Szocska. The success of the Eurotransplant membership of Hungary ever since is also emphasized in the interview with Dr. Zoltán Máthé and the contribution by Sándor Mihály in this book. HISTORY 105

26 Kidney Pancreas TRANSCENDING SELF & NON-SELF The core aim of Eurotransplant is to allocate donor organs following the principle of maximisation of equal opportunities for patients, and to do so by taking into account objective medical criteria as well as individual differences. BASED ON THE experience it had gained with mediating in kidney transplants, Eurotransplant drew up rules for allocating these scarce donor kidneys fairly and efficiently, using medical criteria. As techniques for liver, pancreas, heart and lung transplantation became available, it was self-evident that Eurotransplant would also use its mediating and allocating experience for these organs. Allocation of these organs was, however, less dependent on tissue typing, and determined more by measures to avoid mortality among patients on the waiting list and achieve good long-term survival rates. What has been copied from the kidney allocation system is the principle that allocation has to be done in an ethically acceptable, fair and objective Blood type, tissue characteristics, clinical urgency, waiting time Blood type, (tissue characteristics), clinical urgency, waiting time Heart + Lung Blood type, size of the donor, clinical urgency, waiting time Liver Intestine Blood type, size of the donor, clinical urgency, waiting time Blood type, age and size of the donor, clinical urgency, waiting time Organ Allocation criteria [ET Manual, Chapter 1, p July 2016] way. Matching for these non-renal organs is based not only on blood type and laboratory values, but also on the donor s body height and weight, age and cause of death. In addition, a good match is determined by the physical condition of the recipient and the progression of their organ failure. Whereas tissue compatibility is a purely medically defined allocation criterion, this is much less true for criteria like physique (body-height and -weight). This is why transparency, objectiveness, reliability, justification and validity are core values in Eurotransplant s allocation procedures. The huge gap between the number of patients with a failing organ and the supply of donor organs makes the allocation of donor organs subject to very strict requirements regarding efficiency and public accountability. Although Eurotransplant operates independently from the European Union, the latter has exerted considerable influence since 1990, by means of regulations (Directives). As a result, the rules for donation and transplantation (both national and international) have become much stricter. There are now standards for transparency, fair allocation, traceability of organs and tissues, and reporting and preventing Serious Adverse Events and Reactions (incidents), and there are also active campaigns against commercialisation and the trade in organs. This has led to a more thorough awareness among ET staff of ethical principles and societal considerations. Since the year of the Joint Declaration (2000), Eurotransplant has also formally been to its member states the unique body responsible for the actual distribution of available (solid, non-regenerative) donor organs. The further dissemination and adoption of existing and novel transplantation techniques (including hand/arm transplants, facial transplants and uterus transplants) will lead to ever more centers carrying out transplants. In addition, demographic developments (ageing population, increasing incidence of organ failure) will mean that more people become eligible for transplantation and a place on the waiting list. Hence, the demand for ET s services will grow organically, whereas the supply of available donor organs fluctuates and at best shows marginal growth. In view of the increasing gap between supply and demand, Eurotransplant has to maintain its high standards of transparency and accountability to the outside world. Allocation procedures are continually being adjusted as transplant mediation depends strongly on the number and quality of available donor organs. This availability is closely related to developments in society s medical and ethical views on donorship, life and death and individual responsibility for one s own health. We can therefore be sure that Eurotransplant will continue to adjust its policies over the coming years. This is also borne out by the changes that have been introduced in recent years. Unique aspects of Eurotransplant These 10 chapters have outlined the history of Eurotransplant. To conclude this overview, it should be emphasised that Eurotransplant is in several respects unique among international organ exchange organisations, as it also offers other forms than the so-called standard allocation. One example of this is the High-Urgency / Special- Urgency status and the associated allocation procedure which implies priority over other patients for special reasons. A High Urgency (HU) / Special Urgency (SU) status for a transplant candidate is requested by Current Organ Allocation criteria (ET Manual) 106 EUROTRANSPLANT

27 The Leiden office of Eurotransplant has grown in parallel with the expansion of activities throughout the years. The team focus on the core processes allocation and allocation development the transplant center based on commonly accepted criteria. The request is evaluated by the ET medical staff, as well as members of the organ-specific advisory committee, or by a national or international audit group. Only upon unanimous final approval will the higher allocation priority be granted. Such super-urgent patients thus get priority; a truly life-saving decision. This procedure is unique in the world of transplant medicine. Hence, it is essential to apply very strict criteria for awarding such an urgency status criteria, which have been approved by all ET competent authorities so that the decision can be justified with respect to other patients. A second exceptional aspect of Eurotransplant regards its responsibility for allocating organs from donors with special characteristics. There may be reasons why it is very difficult to select a suitable potential recipient for a donor organ, for example because the donor has a rare blood type. There might be very few potential recipients with that same blood type, also because organ-specific blood group rules allow transplantation of compatible blood groups for these patients. However, it would be wrong to let an organ from a donor with such a rare blood group needlessly go to waste just because there is no suitable recipient on the Eurotransplant waiting list. Eurotransplant therefore has the responsibility to look after having checked its own waiting list for a suitable potential recipient among sister organisations in Europe. The same goes for donor organs derived from children. All efforts will be made to prevent that donor organs have to be discarded. Thus, the core ambition of Eurotransplant remains to allocate donor organs following the principle of maximisation of equal opportunities for patients, and to do so by taking into account objective medical criteria as well as individual differences as approved by the competent authorities of the Eurotransplant countries. The allocation procedures are highly standardised in order to be as objective as possible. Procedures for high-urgency and non-standard criteria organs show that in the end the efforts of Eurotransplant are truly patient-oriented. Its mission today has by all means far exceeded the initial idea of allocation based on histocompatibility criteria alone. HISTORY 107

28 THE FEW REPRESENTING THE MANY INTRODUCTION TO EIGHT SELECTED BIOGRAPHIES Eurotransplant s development and growth are the outcome of the commitment, support and input of many professionals in our field. As it is impossible to mention all those who have made invaluable contributions to the expansion of Eurotransplant in the past 50 years, we have decided to include a biography of one major player from each Eurotransplant Member State. Eurotransplant greatly values and appreciates the involvement and cooperation of these high-level professionals, who played major roles in establishing and further developing the international cooperation within Eurotransplant. CROATIA MIRELA BUŠIĆ MIRELA BUŠIĆ (1964) obtained her medical degree from the University of Zagreb in 1989 and specialised in epidemiology at the same university in In 2002, she became a member of the Croatian National Transplant Board, and was appointed National Transplant coordinator in Ever since, she has led the development of a very successful organ donation and transplantation programme in that country, which at the time aimed at self-sufficiency. In 2006, she was appointed member of the negotiating team for the Accession of the Republic of Croatia to the European Union. Furthermore, she was closely involved in the negotiations and preparation for the Croatian membership in Eurotransplant, which succeeded in the full membership on 27 May From 2001 on, she has held various advisory functions at the Ministry of Health of the Republic of Croatia, including National Transplant coordinator, head of the Department for Special Health Care and Transplantation, director of the Regional Health Development Centre on Organ Donation and Transplant Medicine, as well as acting director of the Institute for Transplantation and Biomedicine. During the now ten years of Eurotransplant membership, Croatia has remarkably boosted its donation and transplantation rates. By 2016, the donor rate had reached 35 per million population (pmp), among the highest in Europe and by far the best performance within Eurotransplant. And Mirela Bušic together with her highly motivated co-workers in the Ministry of Health and the professionals in the transplant centers has been one of the driving forces behind the success. Dr. Bušic has represented Croatia in the Eurotransplant Board from 2006 to 2012, at first as an observer during the preliminary membership time, thereafter as a full member. For her efforts to realise the incorporation of Croatia into Eurotransplant, Mirela Bušić was honoured with the 2012 Eurotransplant Award. 108 EUROTRANSPLANT

29 LUXEMBOURG STANISLAS LAMY STANISLAS LAMY (1944) was born in Arlon (Belgium) but has Luxembourgish nationality. He earned his MD in urology in 1969 at the Catholic University of Louvain, Belgium. After a few years as resident in General Surgery at Chatelet (Belgium), he moved west. Between 1971 and 1976, he held three different residencies in the United States of America. It was in New Orleans that he received his training in transplantation. In late 1976, the Centre Hospitalier de Luxembourg, a brand new hospital building, opened its doors. Staff was recruited, among them Stanislas Lamy. Close colleagues were Henri Kuntziger, specialist in internal medicine and nephrology formerly at Hôpital Tenon in Paris, and François Hentges, specialist in internal medicine with laboratory training in immunology at the Inselspital Bern in Switzerland. Until that moment, Luxembourg kidney patients had been transplanted abroad, often in Belgium, with kidneys offered through Eurotransplant. In 1977, these three doctors drove to Leiden, with the intention that Luxembourg should join the Eurotransplant community. In Belgium, they had consulted Prof. Guy Alexandre about their efforts. Back in Luxembourg, they received a shipment containing the Eurotransplant serum set. These biologics were a conditio sine qua non for obtaining comparable tissue typing data on donors and recipients. As a following step it only took the anaesthetists and intensive care colleagues a short while to work out the organ retrieval protocols. In 1978 Luxembourg became full member of Eurotransplant. Only in 1980 the first kidney transplantation was performed in the state. In 1979, Stanislas Lamy had become head of the Department of Urology and therefore responsible for kidney transplantation at the aforementioned Centre Hospitalier de Luxembourg. Since 1987, Prof. Lamy has been president of Luxembourg Transplant. Although Henri Kuntziger, a major driving force in matters of transplantation, left for Paris in 1987, the transplantation programme developed satisfactorily alongside the many daily activities of the different members of the transplantation staff. However, when Stanislas Lamy stepped back as transplantation urologist in 2008, he was not replaced by a transplant surgeon. Patients were again enrolled on foreign transplantation lists and organ retrieval relied mainly on the transplantation team from Brussels. Prof. Lamy officially retired in August HISTORY 109

30 AUSTRIA RAIMUND MARGREITER RAIMUND MARGREITER (1941) was born in Fügen in the Austrian Zillertal. He obtained his medical degree in Innsbruck in After having been employed in Salzburg, he returned to Innsbruck in 1967 to take up a fellowship in Surgery, and completed his training at the University Hospital of Surgery in His habilitation followed in 1980, and in 1982 Margreiter was appointed head of the Department of Transplant Surgery at the University Clinic for Surgery. In 1999, he became chairman of the Department of Visceral, Transplant and Thoracic Surgery at University Hospital Innsbruck. In addition to his work as a doctor, Margreiter was also active in molecular and cell biology research. His name is closely connected to the Tyrolean Cancer Research Institute (TKFI) and the Daniel Swarovski Research Laboratory. Margreiter acquired his knowledge of transplantation medicine largely through self-study. He was able to build up a single unit in which every type of organ failure could be treated either temporarily by devices, or permanently through all kinds of transplants. With his team he performed the first successful kidney transplant locally in In 1977 he initiated a liver transplant programme and two years later a pancreas transplant programme. Together with oncologists, he performed the first combined liver bone marrow transplantation ever in In the following year, he carried out the first heart transplant in Austria and only a few weeks later the first combined liver kidney transplantation worldwide. In 1985 he managed to complete the first Austrian heart lung transplant and in 1987 the first double lung transplant within Eurotransplant. His first successful multivisceral transplantation worldwide in 1989 attracted international attention. In 1994, he was the first in Austria to carry out isolated intestinal transplantation, and one year later together with his colleagues an islet cell transplantation and the first liver live donation in his country. In the same year, he accomplished the first cluster transplantation within ET, followed in 2000 by the second double hand transplantation and in 2003 by the first double forearm transplantation ever, performed by a large team including reconstructive and hand surgeons. Apart from his medical achievements, Raimund Margreiter was also a keen mountaineer and adventurer. He initiated the Eurotransplant Winter Meetings in Fügen and organised these scientific meetings 22 times. In honour of his efforts, he was awarded the honorary chairmanship of the ET Winter Meetings. He stepped down as chairman of the Eurotransplant Assembly in 2006, after having served for a period of 10 years. He has influenced and trained entire generations of surgeons, and the new, modern Surgical School Innsbruck was the result of his efforts. He retired in October EUROTRANSPLANT

31 HUNGARY FERENC PERNER FERENC PERNER (1937) was born in Budapest, He completed his medical studies at the Semmelweis University in Budapest in 1962 with additional specialist appointments in surgery (1966), traumatology (1972) and nephrology (1985). He travelled widely and studied in Leipzig, Cambridge, Brussels, Maastricht, Groningen, Frankfurt, Seattle, San Francisco, Birmingham, Vienna, Barcelona, Houston and Toronto. He became a Candidate of Medical Sciences in 1977 and a Doctor of Medical Sciences in His two daughters also became medical doctors. The first kidney transplant in Hungary was performed in 1962 by Dr. András Németh, urologist-surgeon, using a living donor kidney, in Szeged. The regular kidney transplantation programme in Hungary was started in 1973 by Ferenc Perner in Budapest. Although the first liver transplant in Hungary was performed in 1983, a regular liver programme was only started by Perner in This was followed by the first heart transplant in 1992, at Semmelweis University (Dr. Zoltán Szabó), and by the first simultaneous kidney pancreas transplant in 1998, at Pécs (Dr. Károly Kalmár Nagy). Perner was the founder and first head of the Department of Transplantation and Surgery at Semmelweis University. The establishment of the first Hungarian independent organisation for donor coordination stimulated renewed negotiations for membership of Eurotransplant (the first were held in 1997). Unfortunately, the professional community was divided, so it was not possible to join at that time. However, a delegation from Hungary, headed by Prof. Perner, visited the Eurotransplant office in Leiden in November 2010, investigating the possibility of cooperation. A few months later, negotiations between ET and the Hungarian government were started. Although some hurdles still had to be overcome, Hungary became a provisional member of the Eurotransplant International Foundation on 1 January 2012, and a full member on 27 May HISTORY 111

32 GERMANY RUDOLF PICHLMAYR RUDOLF PICHLMAYR (1932) grew up in Munich, received his university medical training in the early 1950s and later obtained his doctorate and received his specialist surgical training at the Surgical Clinic of the Munich Ludwig-Maximilians University. As an assistant to Rudolf Zenker in the 1960s, he developed an interest in the treatment of immunological problems, such as rejection reactions after allotransplantation. In 1967, he published his work on anti-dog lymphocyte sera, which represented an important step in the early development of immunosuppressive treatment. The following year he went to Hanover to work as a general and transplant surgeon, where he helped to set up the Transplantation Department at the Hannover Medical School. After being given a professorship and becoming head of Department in 1969, he was appointed full professor in 1973, holding the Chair of Abdominal and Transplant Surgery at the Hannover Medical School (MHH), where he worked until his untimely death. The name Rudolf Pichlmayr is inseparably linked with the development of transplantation medicine in Germany. It was under his leadership that the transplantation department at Hannover became one of the leading centers in the world for research in transplantationm medicine. A number of innovative transplantation techniques were developed there. In 1988, Pichlmayr performed the first split-liver transplant in the world. He was also one of the first to work towards achieving social acceptance for organ donation and organ transplantation, and also advanced the field of organ transplants in Germany through his work in numerous institutions. Under his direction, Hannover became one of the largest transplant centers in Europe. Pichlmayr was a member of the scientific advisory board of the German Medical Association and chairman of its working party on organ transplantation, member of the scientific advisory board of the Kuratorium für Dialyse und Transplantation, member and Chairman of the Board of the Deutsche Stiftung Organtransplantation and, last but not least, member of the Eurotransplant International Board since 1982 until On the research side, Pichlmayr worked tirelessly to improve the practice of kidney transplantation, as well as to further develop liver transplantation and to improve immunological and clinical aspects of immunosuppression after transplantation. He also devoted his efforts to the physical and mental rehabilitation of children and adolescents after transplantation. Rudolf Pichlmayr died tragically on 29 August 1997 during the 37th World Congress of Surgery in Acapulco. 112 EUROTRANSPLANT

33 THE NETHERLANDS JON VAN ROOD JOHANNES [JON] J. VAN ROOD (1926) was born in The Hague. He studied medicine at the University of Leiden and in 1957 became a specialist in internal medicine and head of the Blood Bank of Leiden University Hospital. After receiving his doctorate in 1962 with a thesis entitled Leucocyte Grouping: A Method and its Application he worked for a year at the Immunology Department of the Public Health Research Institute in New York. He then returned to Leiden, where he was appointed professor of Internal Medicine in From 1976 until his retirement in 1991, he was the director of the Haematology Department of Leiden University Hospital. He was one of the founders of the Leiden Institute for Immunology. In 1967, Professor van Rood founded the Eurotransplant organisation, and in 1985 the European Foundation for Immunogenetics, of which he became the chairman. In 1978, he became a member of the Royal Netherlands Academy of Arts and Sciences, and was also awarded the Wolf Prize in Medicine for his contribution to understanding the complexity of the HLA system and its implications for transplantation and disease. The Wolf award was simultaneously awarded to George D. Snell and Jean Dausset. For his outstanding contribution to science and health care, Jon van Rood has been awarded numerous prestigious prizes and distinctions. In the field of immunohematology, the discovery and characterisation of the HLA system has been especially significant in the development of transplantation medicine. After the discovery of the first genetically determined HLA antigen, a systematic computerised analysis of the specificity of antibodies identified tissue antigens determined by the HLA system. This enabled van Rood and his co-workers to discover nine different HLA antigens, which became the basis for the HLA matching and allocation system in organ transplantation. A unique characteristic of Jon van Rood s work was the way in which he time and again was able to translate basic scientific research into practical applications in clinical care. Thus, he was also closely involved in the development of bone marrow (stem cell) transplantation for haemato-oncological disorders. In 1988, he founded the Europdonor organisation (now Matchis) and Bone Marrow Donors World Wide, to provide haemato-oncological patients with matching donors. In addition to its value for kidney, heart and bone-marrow transplants and blood transfusions, Jon van Rood s work has provided new insights into the relation between HLA genotypes and predisposition to disease. He died unexpectedly on 21 July 2017, just before the 50th anniversary of Eurotransplant. HISTORY 113

34 BELGIUM YVES VANRENTERGHEM YVES VANRENTERGHEM (1948) was born in Bruges and started his medical career in 1973, when he obtained his MD degree at the Catholic University of Leuven. Five years later, he completed his training as a nephrologist at the Leuven University Hospital and became a staff member of the Department of Nephrology in that same institution. On 4 November 1963 at the Leuven Hospital, Yves Vanrenterghem performed the first successful renal transplantation. His early career was already characterised by his visionary ideas about the importance of developing effective immunosuppressive therapy in order to ensure long-term graft survival, as well as the value of careful recording of transplantation-related outcome parameters and the development of clinically suitable electronic medical files. In 1988, he was appointed full Professor at the Catholic University of Leuven, and became head of its Department of Nephrology four years later. He became a world-famous expert in the field of renal transplantation, and this reputation has certainly contributed to the fact that he held a prominent position in the Transplantation Society, as well as the vice-chairmanship of the Global Alliance for Transplantation. At the time Yves Vanrenterghem joined the Board of Eurotransplant in 1993, there was a climate of change: Jon van Rood had founded the organisation in 1967 and chaired it for more than 25 years. Eurotransplant had developed from a group of collaborating transplant centers to an international foundation. In September of 1994 the board had accepted major changes in the Articles of Association. The purpose of these changes was to reorganise the foundation s infrastructure, in order to guarantee that the criteria of transparency, democratic involvement of representatives from the different organ transplant programmes and nationalities would be met, so as to meet current and future demands. The new structure of Eurotransplant included an assembly of delegates of all centers cooperating with the organisation, which would meet once a year, having the right to elect the majority of the members of the Board of Management, a Board of Directors and several advisory committees. Thus, with the implementation of these new Articles of Association in early 1995, Eurotransplant entered a second phase in its existence, which also meant that the time had come to hand over the leadership to a new generation. As a first step, taken during the Eurotransplant Winter Meeting in Fügen in January 1995, the board voted to nominate a vice president to assist Jon Van Rood and elected Yves Vanrenterghem. From that time until the end of April 1996, he served as vice president, and on 1 May 1996 he finally took over the presidency from Prof. van Rood and became the second president in the history of Eurotransplant, a position that he held for almost a decade, with strong leadership and vision. He was at the helm of the foundation at the time when Slovenia approached Eurotransplant to become a new member of this international cooperation. He was closely involved in the process and negotiations that resulted in Slovenia joining Eurotransplant in In brief, Yves Vanrenterghem has been member of the Board of Eurotransplant for altogether 16 years, president for nine years, past-president for three years and honorary president thereafter. Prof. Yves Vanrenterghem passed away on 10 September 2013, much too early, at the age of 65 years. 114 EUROTRANSPLANT

35 SLOVENIA JASNA VONČINA JASNA VONČINA (1937) graduated from the Medical Faculty of the University of Ljubljana in 1962, passing her professional medical exam a year later. In 1969, she specialised in anaesthesiology at the University of Zagreb, Croatia, and in 1974 she became head of the newly founded Department of Intensive Therapy of the Ljubljana University Medical Center (UMC). In 1992 she was appointed as a consultant to the General Director of UMC Ljubljana for transplantation activities. She retired in 1993, but is still actively organising transplantation activities. Jasna Vončina has built up close contacts with colleagues at the Leiden University Medical Center. She regularly worked in Leiden as a substitute anaesthesiologist over the years It was during these years that she attended courses such as the European Donor Hospital Educational Programme (Leiden) and Donor Action (Madrid). While she was involved in transplant medicine in general from 1970 on, as of 1986 she also organised a working party in Slovenia on organ procurement from deceased donors, as well as developing protocols for kidney removal. In 1990 she was involved in designing a multi-organ procurement protocol. With 2 million inhabitants, the Slovenian population was too small to sustain a good matching in the kidney transplantation programme, and it certainly could not meet the needs for heart and liver transplantation. Hence, Slovenia started a dialogue with Eurotransplant. In 1994, Vončina became the representative for Slovenia in the European Organization of Transplant Coordinators (EDTCO). In the summer of 1999, negotiations were well on their way for Slovenia to obtain full membership as the sixth member state of Eurotransplant. Full membership was finally realised in the year She was the Slovenian representative on the board from 1999 to In 2007, the ET Board decided to honour Jasna Vončina with the Eurotransplant Award in recognition of all her efforts and dedication to encourage organ transplantation in Slovenia. HISTORY 115