Alvin Schwendener

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 2007 with focus on allogeneic HSCT for AML and novel cellular therapies

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.

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

The 2007 report describes the current status of HSCT activity in Europe, highlights the increasing role of allogeneic HSCT in treatment of AML and gives the first quantitative information on novel cellular therapies. In 2007, there were 25 563 first HSCTs, 10 072 allogeneic (39%), 15 491 autologous (61%) and 3606 additional transplants reported from 613 centers in 42 countries. The main indications were leukemias (8061 (32%; 89% allogeneic)); lymphomas (14 627 (57%; 89% autologous)), solid tumors (1488 (6%; 96% autologous)) and nonmalignant disorders (1302 (5%; 91% allogeneic)). Peripheral blood was the main source of stem cells for autologous HSCT (98%) and the predominant source for allogeneic HSCT (71%). Among allogeneic HSCTs, the number of unrelated donor grafts equaled the number of HLA-identical sibling donor grafts for the first time (47% each). AML was the most frequent indication for allogeneic HSCT (32% of all allogeneic HSCTs), with an increase of 247 (8%). Information on novel cellular therapies was collected for the first time; there were 212 mesenchymal SCTs and 212 HSCTs for nonhematopoietic use. The indications for the latter were cardiovascular disorders (97; 46%), neurological disorders (94; 44%) and tissue repair (21; 10%). These data illustrate the expanding role of cellular therapies.

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

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.

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

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.

Predictability of hematopoietic stem cell transplantation rates

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.

Regime switching based portfolio selection for pension funds

Background and Objectives Hematopoietic stem cell transplantation (HSCT) is a complex and expensive procedure. Trends in the use of this procedure have appeared erratic in the past. Information on future needs is essential for health care administrators. Design and Methods We analyzed the evolution of transplant rates, e.g. numbers of transplants per 10 million inhabitants, in Europe from 1990 to 2004 for all major disease categories and used Gross National Income (GNI) per capita, team density (numbers of teams per 10 million inhabitants) and team distribution (numbers of teams per 10,000 km2) to measure the impact of economic factors in participating countries. Trends were compared by regression analyses, and countries were grouped by World Bank definitions into high, middle and low income categories. Results Transplant rates increased over time with nearly linear trends, in clear association with GNI per capita (R2=0.72), and distinct by World Bank category within a narrow window of variation for both autologous HSCT (R2=0.95, 0.98 and 0.94 for high, middle and low income categories, respectively) and allogeneic HSCT (R2=0.99, 0.96 and 0.95 for high, middle and low income categories, respectively) when breast cancer (autologous) and chronic myeloid leukemia (allogeneic) were excluded. Team density (R2=0.72) and team distribution (R2=0.51) were also associated with transplant rates. Interpretation and Conclusions Transplant rates for HSCT in Europe are highly predictable. They are primarily influenced by GNI per capita. The absence of saturation and a nearly linear trend indicate that infrastructure lags behind medical needs. Isolated changes in single disease entities can easily be recognized.