Michael Gratwohl

Hematopoietic Stem Cell Transplantation: A Global Perspective

CONTEXT Hematopoietic stem cell transplantation (HSCT) requires significant infrastructure. Little is known about HSCT use and the factors associated with it on a global level. OBJECTIVES To determine current use of HSCT to assess differences in its application and to explore associations of macroeconomic factors with transplant rates on a global level. DESIGN, SETTING, AND PATIENTS Retrospective survey study of patients receiving allogeneic and autologous HSCTs for 2006 collected by 1327 centers in 71 participating countries of the Worldwide Network for Blood and Marrow Transplantation. The regional areas used herein are (1) the Americas (the corresponding World Health Organization regions are North and South America); (2) Asia (Southeast Asia and the Western Pacific Region, which includes Australia and New Zealand); (3) Europe (includes Turkey and Israel); and (4) the Eastern Mediterranean and Africa. MAIN OUTCOME MEASURES Transplant rates (number of HSCTs per 10 million inhabitants) by indication, donor type, and country; description of main differences in HSCT use; and macroeconomic factors of reporting countries associated with HSCT rates. RESULTS There were 50 417 first HSCTs; 21 516 allogeneic (43%) and 28 901 autologous (57%). The median HSCT rates varied between regions and countries from 48.5 (range, 2.5-505.4) in the Americas, 184 (range, 0.6-488.5) in Asia, 268.9 (range, 5.7-792.1) in Europe, and 47.7 (range, 2.8-95.3) in the Eastern Mediterranean and Africa. No HSCTs were performed in countries with less than 300,000 inhabitants, smaller than 960 km(2), or having less than US

The EBMT activity survey 2009: trends over the past 5 years

680 gross national income per capita. Use of allogeneic or autologous HSCT, unrelated or family donors for allogeneic HSCT, and proportions of disease indications varied significantly between countries and regions. In linear regression analyses, government health care expenditures (r(2) = 77.33), HSCT team density (indicates the number of transplant teams per 1 million inhabitants; r(2) = 76.28), human development index (r(2) = 74.36), and gross national income per capita (r(2) = 74.04) showed the highest associations with HSCT rates. CONCLUSION Hematopoietic stem cell transplantation is used for a broad spectrum of indications worldwide, but most frequently in countries with higher gross national incomes, higher governmental health care expenditures, and higher team densities.

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

Six hundred and twenty-four centers from 43 countries reported a total of 31 322 hematopoietic SCT (HSCT) to this 2009 European Group for Blood and Marrow Transplantation (EBMT) survey with 28 033 first transplants (41% allogeneic, 59% autologous). The main indications were leukemias (31%; 92% allogeneic), lymphomas (58%; 12% allogeneic), solid tumors (5%; 6% allogeneic) and non-malignant disorders (6%; 88% allogeneic). There were more unrelated than HLA-identical sibling donors (51 vs 43%) for allogeneic HSCT; the proportion of peripheral blood as stem cell source was 99% for autologous and 71% for allogeneic HSCT. Allogeneic and autologous HSCT continued to increase by about 1000 HSCT per year since 2004. Patterns of increase were distinct and different. In a trend analysis, allogeneic HSCT increased in all World Bank Categories (P=0.01, two sided; all categories), autologous HSCT increased in middle- (P=0.01, two sided) and low-income (P=0.01, two sided) countries. EBMT practice guidelines appeared to have an impact on trend, with a clear increase in absolute numbers within the categories ‘standard’ and ‘clinical option’ for both allogeneic and autologous HSCT (P=0.01, two sided; for both allogeneic and autologous HSCT) and a clear decrease in autologous HSCT for the ‘developmental’ and ‘generally not recommended’ indications (P=0.01, two sided). These data illustrate the status and trends of HST in Europe.

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

BACKGROUND The 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. METHODS Between 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. FINDINGS 953,651 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

Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study

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. INTERPRETATION Our 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. FUNDING Funding for this study was indirectly provided by support of the WBMT.

The EBMT activity survey 2008: impact of team size, team density and new trends

Data on 68 146 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 16 433 donors than related 15 493 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.

Hematopoietic stem cell transplants for chronic myeloid leukemia in Europe—Impact of cost considerations

Fifty-five years after publication of the first hematopoietic stem cell transplantation this technique has become an accepted treatment option for defined hematologic and non-hematologic disorders. There is considerable interest in understanding differences in its use and trends on a global level and the macro-economic factors associated with these differences. Data on the numbers of hematopoietic stem cell transplants performed in the 3-year period 2006–2008 were obtained from Worldwide Network for Blood and Marrow Transplantation member registries and from transplant centers in countries without registries. Population and macro-economic data were collected from the World Bank and from the International Monetary Fund. Transplant rates were analyzed by indication, donor type, country, and World Health Organization regional offices areas and related to selected health care indicators using single and multiple linear regression analyses. Data from a total of 146,808 patients were reported by 1,411 teams from 72 countries over five continents. The annual number of transplants increased worldwide with the highest relative increase in the Asia Pacific region. Transplant rates increased preferentially in high income countries (P=0.02), not in low or medium income countries. Allogeneic transplants increased for myelodysplasia, chronic lymphocytic leukemia, acute leukemias, and non-malignant diseases but decreased for chronic myelogenous leukemia. Autologous transplants increased for autoimmune and lymphoproliferative diseases but decreased for leukemias and solid tumors. Transplant rates (P<0.01), donor type (P<0.01) aand disease indications (P<0.01) differed significantly between countries and regions. Transplant rates were associated with Gross National Income/capita (P<0.01) but showed a wide variation of explanatory content by donor type, disease indication and World Health Organization region. Hematopoietic stem cell transplantation activity is increasing worldwide. The preferential increase in high income countries, the widening gap between low and high income countries and the significant regional differences suggest that different strategies are required in individual countries to foster hematopoietic stem cell transplantation as an efficient and cost-effective treatment modality.

Changes in the use of hematopoietic stem cell transplantation : a model for diffusion of medical technology

Six hundred and fifteen centers from 45 countries reported a total 30 293 HSCT to this 2008 EBMT survey with 26 810 first transplants (40% allogeneic, 60% autologous). This corresponds to an increase of 7% for the allogeneic and 3% for the autologous HSCT. Main indications were leukemias (32%; 89% allogeneic); lymphomas (56%; 89% autologous); solid tumors (6%; 96% autologous); and non-malignant disorders (6%; 88% allogeneic). There were more unrelated than HLA-identical sibling donors (49 vs 46%). The proportion of peripheral blood transplants remained stable with 99% for autologous and 70% for allogeneic HSCT. One fifth of the teams with >80 HSCT performed more than half of all HSCT. This trend towards teams with higher numbers of HSCT was stronger for allogeneic (Gini coefficient 57%) than for autologous HSCT (Gini coefficient 38%). Transplant rates (number of transplants per 10 million inhabitants) increased in a close to linear way with increasing team density (number of transplant teams per 10 million inhabitants) and without saturation (R2=0.54); this connection was even stronger for allogeneic HSCT (R2=0.67). These data illustrate status and trends for HSCT in Europe. They provide a rational basis for planning and patient counseling.

Predictability of hematopoietic stem cell transplantation rates

The tradeoff between ongoing expensive drug therapies in general or once in a lifetime procedure becomes relevant. Transplant rates for chronic myeloid leukemia across Europe provide an example. Economics matter as well as evidence.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Background Innovations in hematology spread rapidly. Factors affecting the speed of introduction, international diffusion, and durability of use of innovations are, however, poorly understood. Design and Methods We used data on 251,106 hematopoietic stem cell transplants from 591 teams in 36 European countries to analyze the increase and decrease in such transplants for breast cancer and chronic myeloid leukemia and the replacement of bone marrow by peripheral blood as the source of stem cells as processes of diffusion. Regression analyses were used to measure the quantitative impact of defined macro- and microeconomic factors, to look for significant associations (t-test), and to describe the coefficient of determination or explanatory content (R2). Results Gross national income per capita, World Bank category, team density, team distribution, team size, team experience and, team innovator status were all significantly associated with some or all of the changes. The analyses revealed different patterns of associations and a wide range of explanatory content. Macro- and micro-economic factors were sufficient to explain the increase of allogeneic hematopoietic stem cell transplants in general (R2 = 78.41%) and for chronic myeloid leukemia in particular (R2 = 79.39%). They were insufficient to explain the changes in stem cell source (R2 =26.79% autologous hematopoietic stem cell transplants; R2 = 9.67% allogeneic hematopoietic stem cell transplants) or the decreases in hematopoietic stem cell transplants (R2 =10.22% breast cancer; R2=33.17% chronic myeloid leukemia). Conclusions The diffusion of hematopoietic stem cell transplants is more complex than previously thought. Availability of resources, evidence, external regulations and, expectations were identified as key determinants. These data might serve as a model for diffusion of medical technology in general.