José Nunez

One million haemopoietic stem-cell transplants: a retrospective observational study

BACKGROUNDnThe transplantation of cells, tissues, and organs has been recognised by WHO as an important medical task for its member states; however, information about how to best organise transplantation is scarce. We aimed to document the activity worldwide from the beginning of transplantation and search for region adapted indications and associations between transplant rates and macroeconomics.nnnMETHODSnBetween Jan 1, 2006, and Dec 31, 2014, the Worldwide Network for Blood and Marrow Transplantation collected data for the evolution of haemopoietic stem-cell transplantation (HSCT) activity and volunteer donors in the 194 WHO member states.nnnFINDINGSn953,651 HSCTs (553,350 [58%] autologous and 400,301 [42%] allogeneic) were reported by 1516 transplant centres from 75 countries. No transplants were done in countries with fewer than 300,000 inhabitants, a surface area less than 700 km(2), and a gross national income per person of US

Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey

1260 or lower. Use of HSCT increased from the first transplant in 1957 to almost 10,000 by 1985. We recorded a cumulative total of about 100,000 transplants by 1995, and an estimated 1 million by December, 2012. Unrelated donor registries contributed 22·3 million typed volunteer donors and 645,646 cord blood products by 2012. Numbers of allogeneic HSCTs increased in the past 35 years with no signs of saturation (R(2)=0·989). Transplant rates were higher in countries with more resources, more transplant teams, and an unrelated donor infrastructure.nnnINTERPRETATIONnOur findings show achievements and high unmet needs and give guidance for decisions; to grant access for patients, to provide a donor infrastructure, and to limit overuse by defining risk and region adapted indications for HSCT as an efficient and cost-effective approach for life-threatening, potentially curable diseases.nnnFUNDINGnFunding for this study was indirectly provided by support of the WBMT.

The global diffusion of organ transplantation: trends, drivers and policy implications

Data on 68u2009146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16u2009433 donors than related 15u2009493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.

Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme

Abstract Rising incomes, the spread of personal insurance, lifestyle factors adding to the burden of illness, ageing populations, globalization and skills transfer within the medical community have increased worldwide demand for organ transplantation. The Global Observatory on Donation and Transplantation, which was built in response to World Health Assembly resolution WHA57.18, has conducted ongoing documentation of global transplantation activities since 2007. In this paper, we use the Global Observatory’s data to describe the current distribution of – and trends in – transplantation activities and to evaluate the role of health systems factors and macroeconomics in the diffusion of transplantation technology. We then consider the implications of our results for health policies relating to organ donation and transplantation. Of the World Health Organization’s Member States, most now engage in organ transplantation and more than a third performed deceased donor transplantation in 2011. In general, the Member States that engage in organ transplantation have greater access to physician services and greater total health spending per capita than the Member States where organ transplantation is not performed. The provision of deceased donor transplantation was closely associated with high levels of gross national income per capita. There are several ways in which governments can support the ethical development of organ donation and transplantation programmes. Specifically, they can ensure that appropriate legislation, regulation and oversight are in place, and monitor donation and transplantation activities, practices and outcomes. Moreover, they can allocate resources towards the training of specialist physicians, surgeons and transplant coordinators, and implement a professional donor-procurement network.

Latin America: the next region for haematopoietic transplant progress

The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death (DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes.

Preclinical experience in transplant with lung obtained from non heart beating donors

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009–2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11u2009519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5–8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3–4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

Worldwide distribution of solid organ transplantation and access of population to those practices

describe LTx outcomes. Results: Since 1990 743 LTx donor referrals to The Alfred were reviewed and 73 reported a history of asthma(HoA). From 12/73 referrals where the donor died of asthma (mean age 21, mean p02 505mmHg), 2 double LTx(DLTx) were performed. Of remaining 61 referrals, 25 became lung donors (mean age 28.5 12, mean p02 486 84mmHg) all having a HoA (17 treated) but died from other causes. From these donors, 33 LTx were performed;16 DLTx and 17 single LTx(SLTx). For all 35 LTx recipients from these donors (mean age 49.5 12.3, 19 female) median ICU and hospital stay were 8.1days (range 2-72) and 26.5 days (range 2-72) respectively. Comparing LTx outcomes from donors with treated asthma versus those not on treatment there was a significant difference in last p02 of donors (457 74mmHg vs 531 80mmHg, p 0.05), however no significant difference in % predicted 6 months post op FEV1 (70 19 vs 66 25), ICU and hospital stay. 5 recipients died within 30 days (3 early graft failure) 6 died later (2 due to BOS). 30 day, 1 year, and 5 year survival rates were 86%, 76%, and 70% respectively, no different to our overall LTx outcomes. 26 asthmatic donors with pO2 300mmHg, who died of other causes, were not utilised for LTx. Reasons for this were often complex but a history of asthma alone may have precluded their use in the early years of our program. Conclusion: We have insufficient data to comment on the use of donors who have died of severe asthma. However we have seen an increase in asthmatic donor referrals (3 in 1990-91 up to 16 in 2001-02) and with appropriate selection/utilisation, these lung donors have increased the donor pool with excellent long-term outcomes.

Minimizing Risks in Organ Transplantation: Notify Project New Developments

Introduction The Global Observatory on Donation and Transplantation (GODT) is a collaborative effort of the World Health Organization and the Organización Nacional de Trasplantes of Spain. It is running since 2007 in response to the request of the World Health Assembly, in Resolutions WHA57.18 and 63.22, to collect global data on the practices, safety, quality, efficacy, epidemiology and ethical issues of allogeneic transplantation.This database is recognized as a tool for ensuring transparency, equity and monitoring national transplant systems. Objective To know the distribution of organ transplantation activities among the countries that report data to the GODT, and to assess the access to such practices around the world. Methods An ad hoc standard questionnaire is annually distributed to the identified health authorities and focal points contributing to the global database in each Member State (MS). The United Nations Population Fund report is used as the data source of population. Results Data of 111 MS have been analysed to describe the organ transplant activities in 2015(82.2% of the global population). 126,670 solid organs transplants were reported: 84,347 kidney (41.8% from living donors), 27,759 liver (21.0% from living donors), 7,023 heart, 5,046 lung, 2,299 pancreas and 196 small bowel transplants. Table 1 shows the absolute numbers and organ transplant rates (pmp) in the six WHO regions by applying the total regional population as the denominator. Table. No title available. Kidney transplants were performed in 102 countries. Living kidney transplants were carried out in 98 and transplants from deceased donors in 76 countries. There were 16 countries performing only kidney living transplants (6.6% of the global population). 78 countries performed liver transplants during 2015. Liver transplants from living donors were carried out in 59 countries and from deceased donors in 66. There were 12 countries with living liver transplants alone and 19 countries performing only liver transplants from deceased. Heart and lung transplants were reported in 59 and 44 countries respectively. Of the total of lung transplants, 93.7% were from deceased donors. Only Japan, Brazil and Germany reported to perform lung transplants from living donors in 2015. Regarding pancreas transplants, they were carried out in 45 countries while only 15 countries reported small bowel transplants. Table 2 summarizes the distribution of population covered by the different types of organ transplants. Table. No title available. Conclusion The human right to healthcare includes access to transplant therapy when needed. The international variation in solid organ transplantation activity reflects global inequities in access to transplantation but also highlights the potential of different organ donation and transplantation programmes to produce better outcomes. Following the Madrid Resolution requirements, “self-sufficiency” in organ donation and transplantation continues being a common global challenge.

A Global View on Regulatory Issues in Stem Cell Transplantation and Cellular Therapy

Introduction Risks associated with organ transplantation are minimized through quality and safety guidelines and regulations. In the last 10 years, vigilance and surveillance (V&S) have been promoted through legislation and international initiatives to improve safety and quality. The Notify Project is the first global initiative to promote V&S and was initiated in 2010 under the World Health Organization (WHO) Resolution WHA 63.22 which recognizes the need for V&S of adverse occurrences in the therapeutic use of organs, tissues, blood and cells. The WHO and the Italian National Transplant Center (CNT) joined forces to create the Notify Project with the objective to support and improve V&S worldwide. Material and Methods The Notify project has created a series of tools which include: an open-access library of published adverse occurrences including national and international vigilance reports and the publication of a V&S Booklet. Results During 2017, the second edition of the Booklet included blood and updated all the topics including the most recent publications in the field. The Booklet contains information about all types of Medical Products of Human Origin (MPHO) and V&S aspects. The topics developed in the Booklet incorporate the history and general V&S overview; aspects on global governance of MPHO; organization and key factors for an effective V&S system; responsibilities; clinical practice surveillance; quality management; risks associated for every MPHO; triggers for a national adverse occurrence notification; review of the most common transmissible diseases, protocols for its investigation and tools for learning from errors. Conclusions The Notify Project was established to create awareness of V&S worldwide by disseminating a variety of tools. The Library is constantly updated with documented didactic cases of adverse occurrences arising with the clinical application of MPHO. In 2017, the Project has published a new edition of the Notify Booklet, which includes blood, and has the aim to become a unique reference guide for regulators, competent authorities and professionals to develop a well structured, organized and efficient V&S system. International experts from multidisciplinary backgrounds produced this second edition, to ensure the quality and reliability of the Library’s Booklet. The Booklet promotes the involvement of health professionals, competent authorities and scientific societies working on V&S across the globe.

Narrowing the gap for hematopoietic stem cell transplantation in the East-Mediterranean/African region: comparison with global HSCT indications and trends

The transplantation of human organs, tissues, and cells has become an established treatment for many patients worldwide. More than one million stem cell transplantations and a similar number of organ transplantations have been carried out to date, and annual frequency, safety, and outcomes are all increasing steadily. More recently, novel therapeutic products of human origin have been developed for treating patients with otherwise untreatable diseases. These “medical products of human origin” (MPHO) are fundamentally different from other medical products, because they depend on the donation of biological materials from living or deceased persons. New products of this nature require dedicated, up-to-date legislation. The World Health Assembly at the World Health Organization has addressed this need and issued a number of Principles in recent years. Guiding Principles were issued in 1991 and 2010 and a new global consensus is currently under development.