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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-03-0675.

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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2374-2386

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Current trends in hematopoietic stem cell transplantation in Europe

Alois Gratwohl, Helen Baldomero, Bruno Horisberger, Caroline Schmid, Jakob Passweg, and Alvaro Urbano-Ispizua for the Accreditation Committee of the European Group for Blood and Marrow Transplantation (EBMT)

From the Division of Hematology, Department of Internal Medicine and Department of Research, Kantonsspital Basel, Switzerland; Research Institute for Management in Health Care (FMIG), St Gallen, Switzerland; and EBMT Secretariat, Hospital Clinic, Barcelona, Spain.


    Abstract
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

Major changes have occurred in the transplantation of hematopoietic stem cells (HSCs) during the last decade. This report reveals the changes, reflects current status, and provides medium-term projections of HSC transplantation (HSCT) development in Europe. Data on 132 963 patients, 44 165 with allogeneic HSC transplant (33%) and 88 798 with an autologous HSC transplant (67%), collected prospectively from 619 centers by the European Group for Blood and Marrow Transplantation (EBMT) in 35 European countries between 1990 (4234 HSCTs) and 2000 (19 136 HSCTs) illustrate utilization of HSCT. HSCT increased in all European countries and for all indications. There were major differences depending on disease indication and donor type. Transplantation rates (numbers of HSCTs per 10 million inhabitants) varied from less than 1 for some rare indications to 37.7 ± 4.1 for acute myeloid leukemia in allogeneic HSCT or 95.5 ± 13.5 for non-Hodgkin lymphoma in autologous HSCT. There were indications with a steady, continuing increase and others with initial increase but subsequent decrease. Projections on medium-term development for each disease based on a weighted sensitivity analysis predict an ongoing increase in allogeneic HSCT except for chronic myeloid leukemia. In autologous HSCT they predict an increase for lymphoproliferative disorders, acute myeloid leukemia, myelodysplastic syndromes, and some solid tumors but a decrease for most solid tumors, acute lymphoid leukemia, and chronic myeloid leukemia. Transplantation rates can be predicted with reasonable sensitivity for most disease indications. Despite marked changes in the rapidly developing field of HSCT, this information on current use, trends, and midterm predictions forms a rational basis for patient counseling and health care planning. (Blood. 2002;100:2374-2386)

© 2002 by The American Society of Hematology.

    Introduction
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

Transplantation of hematopoietic stem cells (HSCs) is established therapy for many congenital or acquired severe disorders of the hematopoietic system as well as for chemosensitive or radiosensitive malignancies.1-3 Hematopoietic stem cells from bone marrow, peripheral blood, or cord blood are used for autologous or allogeneic HSC transplantation (HSCT).4,5 Donors for allogeneic transplants include HLA-identical siblings, other family members, or unrelated volunteers from the vast worldwide donor pools.6

Major changes have occurred in HSCT over the last decade. Stem cell source has changed from bone marrow to peripheral blood for almost all disease indications in autologous HSCT. In allogeneic HSCT, more than 50% of the HLA-identical sibling transplants, most haploidentical and twin transplants, and more than one third of the unrelated donor transplants were peripheral blood derived in the year 2000.7,8 Expansion of unrelated donor pools to a current state of more than 7.5 million registered donors worldwide, the establishment of cord blood banks in North America and Europe, and successful introduction of haploidentical HSCT have made allogeneic HSCT available to patients without an HLA-identical sibling donor.4,6,9 New technologies, such as reduced-intensity conditioning, limit early toxicity and allow allogeneic HSCT for patients above the previous age limit and for those with concomitant organ toxicity.10,11 At the same time, the role of HSCT has been put to question for certain disease indications. Excessive hopes first put forward HSCT for breast cancer, but frustration about the results then halted its use.12 Furthermore, novel therapeutic strategies have emerged, such as the specific bcr/abl tyrosine kinase inhibitor imatinib mesylate for treatment of chronic myeloid leukemia.13,14 It made an immediate impact on HSCT use for this disease. All these changes occurred in a field of high technology and high-cost medicine. Health care providers, hospital administrators, and reimbursement agencies alike are challenged in this constantly changing field to have the resources available when needed. Correct assessment of current status, trends, and predictions for the near future are essential for planning health care strategies.7

Ten years ago the European Group for Blood and Marrow Transplantation (EBMT) initiated an annual activity survey as a new tool. All HSCTs are registered by disease indication, donor type, and stem cell source on an annual basis.15 Introduced as an instrument for quality control, the activity survey gained rapid acceptance and presently more than 95% of all HSCTs in Europe are covered by this survey. It allows a precise description of current status each year, illustrates differences and similarities between European countries, allows calculations of transplantation rates and team densities between the countries, reveals quantification of consensus for indications, and permits detailed observations of changes in technologies.16,17 As presented in this report, observations over a decade now give a precise assessment of current status for the individual disease indications and permit a forecast with substantial sensitivity for the immediate future.


    Patients and methods
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

Data collection and validation

Data collection is based on the EBMT activity surveys introduced in 1990.15 Since then, all European centers, EBMT members as well as nonmembers, are requested annually to report on a survey sheet the numbers of new patients by indication, stem cell source, and donor type. Transplantations are defined as the infusion of HSCs following a conditioning regimen with the intention of replacing the existing hematopoiesis by injected stem cells. The EBMT survey was adopted by the General Assembly as a mandatory self-reporting system and forms an integral part of a prospective quality assurance program (http://www.EBMT.org). The latter includes revalidation of a computer print-out of entered data by reporting teams, cross-checking with national transplant registries, and on-site visits.

Participating teams

Six hundred nineteen teams in 36 European countries were contacted over time. Five hundred eighty (94% return) replied in 2000. This includes all 470 EBMT member teams. No major transplant team in Europe is missing from this list. In 1990, the report began with 142 teams. The contacted teams are listed in the Appendix in alphabetical order according to country, city, and EBMT center code. In 2000, according to unofficial information received, no blood or marrow transplantations were performed in these European countries: Albania, Andorra, Armenia, Azerbaijan, Bosnia-Herzegovina, Georgia, Iceland, Latvia, Liechtenstein, Malta, Moldavia, Monaco, San Marino, and the Vatican.

Transplantation rates

Transplantation rates were defined as number of HSCTs per 10 million inhabitants. They were computed as previously defined for each year, disease indication, donor type, and country. For each disease indication transplantation rates were assessed for all HSCTs and separately for autologous, allogeneic, and unrelated HSCTs. Population data have been obtained from the US census office (http://www.census.gov) since 1996 and from the annual Fischer Weltalmanach for the years prior to 1996.

Statistical analysis, prediction of transplantation rates, and sensitivity analysis

Mean, median, and SDs of numerical variables were calculated on an Excel spreadsheet. Groups were compared with chi 2 tests.

To assess changes in transplantation rates over time for each disease indication and to recognize trends, the following approach was used. All countries with at least 100 transplantations during all the years since 1990 were selected; these include Belgium, France, Germany, The Netherlands, Switzerland, Italy, Spain, Sweden, and the United Kingdom. For each of these countries transplantation rates were calculated for all indications as listed in Table 1 for autologous HSCT and Table 2 for allogeneic HSCT. For calculations of transplantation rates a weighted analysis was used considering the size of each of the 9 individual countries. For each disease indication weighted means and SDs were calculated and in a regression analysis the best fitting curve was computed.

                              
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Table 1. Indications for allogeneic HSCT in Europe 1990-2000 


                              
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Table 2. Indications for autologous HSCT in Europe 1990-2000 


    Results
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

Development of transplantation activity

The development of HSCT in Europe during the last decade is illustrated in Figure 1. There has been an increase in HSCT activity for both allogeneic and autologous transplants. In 1991, there were equal numbers for both technologies. Autologous HSCT showed a marked increase after 1993, culminating in 1998 with almost 13 000 patients and a decline thereafter. As a total, there were 19 136 first transplantations, including 6404 (33%) allogeneic and 12 732 (67%) autologous HSC transplantations in 2000. 


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Figure 1. Evolution of HSCT in Europe from 1990 to 2000.  Annual numbers of allogeneic and autologous HSCT and of participating teams.

Increase in transplantation activity during the last decade is based both on increase in team numbers and increase in transplantations within participating teams. Teams increased from 143 in 1990 to 619 in 2000. Of those, 579 responded to this survey. Fifty-three percent performed allogeneic and autologous transplantations, 41% restricted their activity to autologous transplantations only, and 2% performed allogeneic transplantations only.

Activity between teams varied widely; 137 (24%) teams performed fewer than 10 transplantations, 128 (22%) teams between 10 and 20 transplantations, 180 (31%) between 20 and 50 transplantations, 107 (18%) between 50 and 100 transplantations, and 27 teams (5%) more than 100 transplantations in 2000.

Indications for HSCT and donor type

Numbers of patients treated with HSCT over the last decade are listed in Tables 1 and 2 according to disease indication and donor type. Table 1 lists the numbers of patients with allogeneic transplants by disease indication as a total for the years 1990-2000 and for the year 2000. Table 2 lists the autologous HSCT. Overall, from 1990 to 2000 there were 132 963 first transplantations in Europe, of which 44 165 (33%) were allogeneic and 88 798 (67%) autologous HSCTs. They are grouped into 4 main disease categories, namely, lymphoproliferative disorders with 52 847 patients (39.7%), leukemias with 48 561 patients (36.5%), solid tumors with 24 288 patients (18.3%), and nonmalignant disorders with 6016 patients (0.5%).

Not all indications increased at the same rate, as given in Tables 1 and 2 and as reflected in Figure 2. Some indications appeared only recently, such as allogeneic HSCT for solid tumors or HSCT for autoimmune disorders. Concerning allogeneic HSCT, a marked increase was observed for leukemias and a relatively stable rate for nonmalignant disorders, including aplastic anemia (Figure 2A). For lymphoproliferative disorders, a trend toward more allogeneic HSCT has been observed during the last 2 years. For autologous HSCT, the pattern is different (Figure 2B). Breast cancer showed a marked increase after 1994 with a peak in 1997 and a continuous decline thereafter, whereas lymphoproliferative disorders and multiple myeloma continue to rise. Lymphoproliferative disorders (lymphoma) showed the most pronounced increase. For leukemias and other solid tumors, there are signs of a plateau developing over the last 2 years.


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Figure 2. Absolute numbers of HSCT in Europe from 1990 to 2000 according to main indications. (A) Allogeneic transplantations for leukemias, lymphoproliferative disorders, and nonmalignant disorders. (B) Autologous transplantations for leukemias, lymphomas, multiple myelomas, breast cancer, and other solid tumors.

There are distinct differences between the disease groups with regard to donor type. Patients with solid tumors were almost exclusively treated with autologous HSCT (98.0%). In contrast, patients with aplastic anemia, hemoglobinopathies, immunodeficiency disorders, or inborn errors, in the group of nonmalignant disorders, almost exclusively underwent allogeneic HSCT (98%-100%). The few patients with congenital disorders and autologous HSCT are those given genetically modified autologous HSC transplants. Patients with lymphoproliferative disorders were treated predominantly with autologous HSCT (92.6%). Similarly, patients with autoimmune disorders were primarily treated with autologous HSCT (92%). Patients with leukemias were mainly treated with allogeneic HSCT (69.0%) even though for some subgroups, such as acute myeloid leukemia, numbers of autologous and allogeneic procedures were equal.

Of the 6404 allogeneic HSCTs in 2000, 3955 (62%) recipients received cells from an HLA-identical sibling donor, 437 (7%) from another family member, 58 (1%) from a syngeneic twin, and 1954 (31%) from an unrelated volunteer donor. Over the decade, the percentage of twin donors has remained stable; the percentage of unrelated donors has increased from less than 10% to more than 30% in 2000.

Stem cell source

Stem cell source varied over time and was dependent on donor type. In 1990, almost all HSC transplants were bone marrow derived. This has changed within the decade. Of the 19 136 HSC transplants in 2000, only 3555 (19%) were still bone marrow derived; 15 581 (81%) were from peripheral blood stem cells or were combined bone marrow and peripheral blood stem cell transplants. There are differences in stem cell source for autologous and allogeneic HSCT. Of the 12 732 autologous HSCTs, only 566 (4%) used bone marrow and 12 166 (96%) used peripheral blood stem cells. Of the 6404 allogeneic HSCTs, 2989 (47%) were bone marrow derived and 3415 (53%) were peripheral blood stem cell transplants. Peripheral blood was used in 57% of HLA-identical sibling donor transplants, in 81% of transplants from other family members, in 76% of twin donors, and in 39% of unrelated donors.

Changes in transplantation rates over time

Transplantation rates differed between the European countries but increased in all European countries over the decade (Figure 3). These rates differed depending on indication, donor type, and time. Changes in transplantation rates for the 9 selected countries described above are given in Tables 3 and 4.


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Figure 3. Transplantation rates in participating European countries in 2000.  Shades reflect number of total HSCTs (autologous and allogeneic) per 10 million inhabitants. (A) Transplantation rates in 1990. (B) Transplantation rates in 2000.


                              
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Table 3. Changes in allogenic HSCT rates from 1990 to 2000 in 9 selected countries with predictions for 2003 


                              
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Table 4. Changes in autologous HSCT rates from 1990 to 2000 in 9 selected countries with predictions for 2003 

For allogeneic HSCT, transplantation rates increased for all indications continuously with 2 exceptions (Table 3): chronic myeloid leukemia and inborn errors, for which the maximum was reached in 1999. For chronic myeloid leukemia, the likely explanation is the advent of imatinib mesylate. For inborn errors, it could be a chance phenomenon at the beginning of stabilization. Mathematical models cannot separate chance variations from first signs of a new trend, but they predict an increase for both indications for 2003. Patterns of increase were not the same for all indications (Figure 4A,B). In aplastic anemia, the increase was relatively small over time with a slow steady increase, and a decrease in SD (trend mean y = 0.0066 ×2 + 0.187x + 4.0116: r2 0.5338); in AML the increase is marked with a doubling of transplantation rate almost every 5 years (trend mean y =0.0961 ×2 + 1.3861x + 11 105; r2 = 0.9973).


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Figure 4. Transplantation rates for selected indications in 9 European countries from 1990 to 2000.  Refer to Figure 3. Weighted transplantation rates (per 10 million inhabitants) are given (black-diamond ) and best fitting curves (lines). (A) Aplastic anemia, allogeneic HSCT. (B) Acute myeloid leukemia, allogeneic HSCT. (C) Multiple myeloma, autologous HSCT. (D) Breast cancer, autologous HSCT.

For autologous HSCT, the changes in transplantation rate differed from the pattern seen in allogeneic HSCT (Table 4). For some indications, a continuous increase occurred throughout the decade. This was the case for lymphoproliferative disorders, as exemplified by the curves for multiple myeloma (Figure 4C) and a doubling every 3 to 4 years (trend mean y = 0.33 ×2 + 4.3538x - 4.0192; r2 = 0.9899). The same trend was observed for some leukemias (myelodysplastic syndromes, chronic lymphocytic leukemia) and some solid tumors (glioma, Ewing sarcoma). In contrast, for other indications, most marked for breast cancer (Figure 4D), the rapid increase in the early 1990s with a peak between 1997 and 1998 was followed by a rapid decline. Mathematical models would even predict a value of 0 at 3 years. Similarly, for chronic myeloid leukemia, predictions cannot yet capture the decline in 2000 and show a continuing rise.


    Discussion
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

These data give an overview of the status of HSCT in Europe during the last decade and today. They illustrate the main changes in technology and the overall increase over time with substantial differences between European countries. They give detailed insight for individual disease indications and allow a precise medium-term forecast.

Based on the analysis of weighted transplantation rates in 9 countries with the highest transplantation numbers, it can be predicted that transplantation rates for allogeneic HSCT will continue at the same or higher level in the immediate future for all indications. Only one exception is chronic myeloid leukemia, which has been the leading indication for allogeneic HSCT up to the year 1999.8,15 It is likely that the decline in 2000 is not a chance phenomenon but due to the introduction of imatinib mesylate, a novel specific tyrosine kinase inhibitor.13,14 It is of interest to note that reduction in transplantation rates for chronic myeloid leukemia occurred before the first publication on the results of the initial phase 1 trial, which were published in the spring of 2001. This sequence of events suggests that anticipation of therapeutic success was a major factor in decision-making. The same phenomenon that changes in transplantation rates occurred before the key publications was observed earlier in the decade with regard to breast cancer. This phenomenon of anticipation needs to be recognized at times of high praise for evidence-based medicine.18 The issue of HSCT for chronic myeloid leukemia is still not settled. Imatinib failures continue to occur and therapists are reverting to HSCT in these cases. More observation time is needed for reevaluation of HSCT in chronic myeloid leukemia.

Predictions in autologous HSCT do not show a general pattern but rather different trends. The situation for autologous HSCT in breast cancer, as mentioned above, has received broad attention beyond the medical literature and was summarized in headlines, such as "transplants decline, research continues."19 Hopes for cure initially stimulated autologous HSCT for breast cancer as well as solid tumors in general.20 Results did not meet expectations and induced a similar, marked decline.21,22 The pattern varies substantially depending on indications. HSCT rates declined for germ cell tumors and acute lymphocytic leukemia. In contrast, they continued for neuroblastoma and Ewing tumors at similar rates and increased for non-Hodgkin lymphoma, multiple myeloma, or acute myeloid leukemia. For the latter 3 indications, autologous HSCT continued to increase with the highest transplantation rates in the year 2000. Importantly, these indications correspond to those where HSCTs were shown to provide a clinical benefit compared to standard therapy in prospective randomized studies.23-26 It is also noteworthy that indications with the highest transplantation rate in 2000 were compatible and concordant with so-called accepted indications for HSCT.3

Health care today has many aspects of a market. Demand is there, if a given technology is recognized as the treatment of choice. Health care providers should be in a position to offer these therapies if the need arises. For high-cost, complex techniques, such as HSCT, planning is essential. Medium-term horizon scanning (http://wwww.bham.ac.uk/PublicHealth/horizon/glossary.htm) has become vital for health care management. Novel tools are required in this field. The annual activity survey of the EBMT presents one such unique instrument. Thanks to a nearly complete coverage of a medical technology across several countries within a continent and the rapid return of information, trends can be discovered very early and predictions can be made with reasonable sensitivity and accuracy.27 The limitation of the approach is that new events, for example, the introduction of a novel drug, such as imatinib mesylate, which can change treatment strategies within 1 year, cannot be anticipated. Despite the best mathematical models, statistical analyses cannot distinguish in the first year between chance events and the beginning of a new era.

Several factors influence transplantation rates for individual disease indications. Prevalence of the disease, consensus on indication, and the economic situation within a country are the main determinants. In addition, the technology has to be available and needs to be disseminated within a country.28 This can clearly be influenced by health care planning even though optimal team density (number of transplantation teams per 10 million inhabitants) needs to be defined.

In summary, these data based on 10 years of cumulative transplantation activity data in Europe show that transplantation rates for individual disease indications can change. Such shifts are not necessarily based on evidence but rather on anticipation. Nevertheless, transplantation rates are not erratic but highly predictable at medium term.


    Acknowledgments

The cooperation of all participating teams and their staff (listed in the Appendix), the EBMT secretariat (A. Urbano-Ispizua, A. Baur), the European EBMT Data Office in Paris (V. Chesnels, P. Palut, N. C. Gorin), the EBMT Registry Subcommittee (P. Ljungman, C. Ruiz de Elvira), the French Registry SFGM (J. P. Vernant, M-L Tanguy), the Dutch Registry (T. de Witte, A. v. Biezen, N. Tazelaar), the Austrian Registry (D. Niederwieser, B. Gritsch), the Italian Registry (M. Vignetti, A. Bacigalupo, R. Oneto, C. Palazzi), the German Registry (H. Ottinger, C. Müller, B. Kubanek, N. Schmitz, U. W. Schaefer), the Swiss Registry (J. Passweg, H. Baldomero), the British Registry, the Belgium Registry, (Y. Beguin) and the Spanish Transplantation Office (ONT) (M. Naya) is greatly appreciated. The authors also thank A. Maerki for excellent secretarial assistance, A. Wodnar-Filipowicz for reviewing the manuscript, as well as L. John and O. Baldomero for technical assistance with data management.


    Footnotes

Submitted May 5, 2002; accepted May 15, 2002.

Prepublished online as Blood First Edition Paper, May 31, 2002; DOI 10.1182/blood-2002-03-0675.

Supported in part by a grant from the Swiss National Research Foundation, 32-52756.97, the Swiss Cancer League, and the Horton Foundation. EBMT is supported by grants from the corporate members: Hoffmann-La Roche Ltd, Amgen Europe, Chugai Rhone-Poulenc Rorer, Baxter, Astra, Cobe International, Nextar, Liposome, Imtix, Octapharma, Stem Cell Technologies, ICN Pharmaceuticals, and Bristol-Meyers Squibb.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.

Reprints: Alois Gratwohl, Kantonsspital Basel, Division of Hematology, Department of Internal Medicine, CH-4031 Basel, Switzerland; e-mail: hematology{at}uhbs.ch.


    References
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

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2. Lennard AL, Jackson GH. Stem cell transplantation. BMJ. 2000;321:433-437[Free Full Text].

3. Goldman JM, Schmitz N, Niethammer D, Gratwohl A, for the Accreditation Subcommittee of the EBMT. Special report. Allogeneic and autologous transplantation for hematological diseases, solid tumors and immune disorders: current practice in Europe in 1998. Bone Marrow Transplant. 1998;21:1-7[CrossRef][Medline] [Order article via Infotrieve].

4. Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med. 1997;337:373-381[Abstract/Free Full Text].

5. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med. 2001;344:175-181[Abstract/Free Full Text].

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8. Gratwohl A, Passweg J, Baldomero H, Urbano-Ispizua AL. Bone marrow transplantation activity in Europe 1999. Report from the European Group for Bone Marrow Transplantation (EBMT). Bone Marrow Transplant. 2001;27:899-916[CrossRef][Medline] [Order article via Infotrieve].

9. Averso F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186-1193[Abstract/Free Full Text].

10. Barrett J, Childs R. Non-myeloablative stem cell transplants. Br J Haematol. 2000;111:6-17[CrossRef][Medline] [Order article via Infotrieve].

11. McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390-3400[Abstract/Free Full Text].

12. Chaos surrounds high-dose chemotherapy for breast cancer [editorial]. Lancet. 1999;353:1633[CrossRef][Medline] [Order article via Infotrieve].

13. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-1042[Abstract/Free Full Text].

14. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031-1037[Abstract/Free Full Text].

15. Gratwohl A. Bone marrow transplantation activity in Europe 1990. Report from the European Group for Bone Marrow Transplantation (EBMT). Bone Marrow Transplant. 1991;8:197-201[Medline] [Order article via Infotrieve].

16. Gratwohl A, Hermans J, Goldman J, Gahrton G. Bone marrow transplantation in Europe. Major geographical differences. J Int Med. 1993;233:333-341[Medline] [Order article via Infotrieve].

17. Gratwohl A, Baldomero H, Hermans J. Quantitative assessment of consensus on indications for blood or marrow transplantation in Europe 1995. Cancer Res Ther Control. 1999;10:123-144.

18. Gratwohl A, Baldomero H, Urbano-Ispizua A. Hematopoietic stem cell transplantation and Gleevec: anticipation as driving force in decision making. Lancet. 2002;359:712-713[Medline] [Order article via Infotrieve].

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21. Stadtmauer EA, O'Neill A, Goldstein LJ, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 2000;342:1069-1076[Abstract/Free Full Text].

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24. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myelome. N Engl J Med. 1996;335:91-97[Abstract/Free Full Text].

25. Matthay KK, Villablanca JG, Seeger RC, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med. 1999;341:1165-1173[Abstract/Free Full Text].

26. Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995;332:217-223[Abstract/Free Full Text].

27. Luce BR, Elixhauser R. Sensitivity analysis. In: Culyer AJ,Horisberger B, eds. Standards for Socioeconomic Evaluation of Health Care Products and Services. Berlin: Springer Verlag; 1999:80-81.

28. Gratwohl A, Passweg J, Baldomero H, Horisberger B, Urbano-Ispizua A, for the Accreditation Committee of the European Group for Blood and Marrow Transplantation (EBMT). Economics, health care systems and utilisation of haematopoietic stem cell transplants in Europe. Br J Haematol. 2002;117:451-458[CrossRef][Medline] [Order article via Infotrieve].


    Appendix
Top
Abstract
Introduction
Patients and methods
Results
Discussion
Appendix
References

List of transplant centers in 2000 (numbers show total number of patients with first transplantations in year 2000 (total number of transplantations) followed by the allografts/autografts). The total number teams in 2000 was 600; total number of transplantations, 22 496 (allo, 7146; auto, 15 350); and total number of first transplantations 19 366 (allo, 6456; auto, 12 910). *indicates no report; dagger late data, included only in Figure 3B.

Albania

No report.

Andorra

No report.

Armenia

No report.

Austria (15 teams; 329 [396], 127/202)dagger

Graz, University Hospital, CIC 308, W. Linkesch (52 [66], 10/42); Graz, University Hospital, Onco, CIC 278, H. Samonigg, M. Schmid (4 [9], 0/4)dagger ; Graz, Universitäts-Kinderklinik, CIC 593, Ch. Urban (12 [13], 5/7)dagger ; Innsbruck, Universitätsspital (hem, onco), CIC 271, G. Gastl, D. Nachbaur (29 [33], 24/5); Innsbruck, Universitätsspital (Internal Medicine), CIC 516, E. Woell (4 [7], 0/4); Klagenfurt, General Hospital Klagenfurt CIC 716, D. Geissler, M. Heistinger (8 [8], 0/8); Linz, 1 Medizinische Abteilung, AO Krankenhaus, M. A. Fridrik (1 [1], 0/1); Linz, AOK der Elisabethinen, CIC 594, D. Lutz, O. Krieger (32 [43], 7/25)dagger ; Salzburg, LKA Salzburg (Onco), CIC 356, Prof. Hausmaninger (10 [10], 0/10); Vienna-Lainz, Krankenhaus der Stadt Wien-Lainz, 5. Med Onko, CIC 362, G. Baumgartner, E. Ulsperger, Dr. Mayer (1 [1] 0/1) ; Vienna, St Anna Kinderspital, CIC 528, H. Gadner, C. Peters (35 [43], 20/15); Vienna, Donauspital, CIC 767, W. Hinterberger (14 [18], 0/14)dagger ; Vienna, Universitätsklinik für Innere Medizin I-AKH, CIC 227, H.T Greinix, P. Kalhs (89 [97], 61/28)dagger ; Vienna, Wilhelminerspital, CIC 828, H. Ludwig (31 [40], 0/31); Vienna, Hanusch-Krankenhaus, CIC 743, R. Reisner, E. Pittermann, E. Koller (9 [10], 0/9).dagger

Azerbaijan

No report.

Republic of Belarus (3 teams; 41 [42], 13/28)

Minsk, Belorussian Center, CIC 591, O. Aleinikova (15 [16], 6/9); Minsk, Hospital No. 9, CIC 801, N. Milanovitch (26 [26], 7/19); Minsk, Institute of Haematology, V. Ivanov ().*

Belgium (24 teams; 553 [647], 170/383)

Aalst, OLV Ziehenhuis, E. Wouters ()*; Antwerpen, AZ Middelheim, CIC 783, R. de Bock (7 [7], 0/7); Antwerpen, Stuivenberg ZH, CIC 339, P. Zachée (35 [41], 6/29); Brugge, AZ St Jan, CIC 506, D. Selleslag, A. Van Hoof (40 [53], 12/28); Brussels, Clinique Général Saint Jean, CIC 779, C. Dubois (4 [7], 0/4); Brussels, Hôpital Erasme, CIC 596, W. Feremans (14 [16], 0/14); Brussels, Clinique universitaire St Luc (Adults), CIC 234, A. Ferrant (49 [52], 26/23); Brussels, Institut Jules Bordet +Children's University Hospital, CIC 215, D. Bron C. Devalck, E. Sariban (48 [56], 24/24); Brussels, University Hospital, CIC 630, B. Van Camp, A. Schots (25 [25], 12/13); Brussels, Cliniques Universitaires St Luc, (onco), M. Symann (3 [3], 0/3); Brussels, Institute Edith Cavelle Marie Depage (onco), C. Vanhaelen ()*; Brussels, Clinique Universitaire St Luc (peds), CIC 234, C. Vermylen (13 [13], 6/7); Charleroi, Hopital Notre-Dame, M. André (27 [29], 1/26); Edegem, University Antwerpen, CIC 648, W. Schroyens (26 [28], 3/23); Gent, University Hospital, CIC 744, L. A. Noens (50 [53], 20/30); Haine, St Paul, Hôpital de Jolimont, CIC 234, A. Delannoy, C. Ravoet (13 [16], 0/13); Hasselt, Virgajesse Ziekenhuis CIC 632, D. Vanstraelen, Dr. Janssen (25 [27], 0/25); Jumet, Hôpital Civil de Jumet, A. Duvivier ()*; Leuven, University Hospital Gasthuisberg, CIC 209, M. A. Boogaerts, P. Vandenberghe, J. Maertens (76 [89], 29/47); Liège, University Hospital Sart-Tilman, CIC 726, Y. Béguin (49 [71], 20/29); Liège, CHR-Citadelle, CIC 353, B. De Prijck (6 [7], 0/6); Liège, Centre Hospitalier St Joseph (hem), L. Longree ()*; Roeselare, H. Hartziekenhuis, F. Van Aelst, J. Tytgat, J. Demol (13 [14], 2/11); Yvoir, Clinique universitaire de Mont-Godinne CIC 234, C. Doyen (30 [40], 9/21).

Bosnia-Herzegovina

No report.

Bulgaria (1 team; 15 [15], 3/12)

Sofia, Uni Hospital "Queen Johanna," CIC 346, (peds hem-onco), D. Bobev (15 [15], 3/12).

Croatia (2 teams; 93 [99], 24/69)

Zagreb, Hospital Merkur, CIC 159, B. Jaksic, H. Minigo (21 [21], 1/20); Zagreb, Clinical Hospital Center, CIC 302, B. Labar, D. Nemet, M. Mrsic (72 [78], 23/49).dagger

Cyprus (1 team; 14 [14], 0/14)

Nicosia Makarious Hospital lll, N. Papaminas (14 [14], 0/14).

Czech Republic (10 teams; 392 [465], 103/289)

Brno, Masaryk University Hospital, CIC 597, J. Vorlicek (75 [91], 18/57); Hradec Kralové, Charles University, CIC 729, S. Filip, M. Blaha (51 [59], 10/41); Olomouc, University Hospital, CIC 574, K. Indràk (52 [61], 10/42); Pilsen, Faculty Hospital, CIC 718, V. Koza (62 [67], 19/43); Prague, Thomayer Memorial Hospital, CIC 375, J. Abrahamova, J. Nepomucka, L. Boublikova (7 [8], 0/7); Prague, University Hospital Motol (peds onco), P. Kavan (22 [25], 0/22); Prague, Clinical Haematology, Charles University, CIC 318, T. Kozak (22 [29], 0/22); Prague, University Hospital Motol (peds hem), CIC 656, J. Stary (21 [23], 20/1); Prague, Charles University, CIC 745, M. Trneny (47 [66], 0/47); Prague, Institute of Hematology and Blood Transfusion, CIC 656, A. Vitek, P. Kobylka (33 [36], 26/7).

Denmark (3 teams; 161 [179], 47/114)

Aarhus, Amtssygehus, CIC 634, A. Boesen (38 [43], 0/38); Copenhagen, Rigshospitalet, CIC 206, N. Jacobsen (93 [100], 47/46); Copenhagen, Herlev Hospital, University, CIC 568, H. E. Johnson (30 [36], 0/30).

Estonia (1 team; 16 [16], 1/15)

Tartu, University Hospital, CIC 746, H. Everaus (16 [16], 1/15).

Finland (7 teams; 248 [271], 99/149)

Helsinki, University Hospital, Department Oncology, CIC 833, H. Joensuu, T. Wiklund (12 [13], 0/12); Helsinki, University Hospital, Third Department of Medicine, CIC 515, T. Ruutu (88 [91], 63/25); Helsinki, Children's Hospital, CIC 219, U. Pihkala, S. Vettenranta (28 [32], 18/10); Kuopio, Department of Medicine, University Hospital, E. Jantunen, T. Nousiainen (28 [28], 0/28); Oulu, University Central Hospital (haem/onco), CIC 690, P. Koistinen, T. Turpeenniemi-Hujanen (20 [20], 0/20); Tampere, University Hospital, CIC 635, E. Koivunen, R. Silvennoinen (30 [41], 0/30)dagger ; Turku, University Central Hospital, CIC 225, K. Remes (42 [46], 18/24).

France (85 teams; 3103 [3624], 711/2392)dagger

Amiens, CHU d'Amiens, B. Desablens, ()*; Angers, Paul Papin, Dr Gamelin ()* Angers, Centre Hospitalier, CIC 650, N. Ifrah (53 [64], 12/41); Argenteuil, Centre hospitalier, M. Urbajtel (28 [28], 7/21); Besançon, Hôpital Jean Minjoz and Hôpital St Jacques (adults and peds), CIC 233, P. Hervé, J.-Y. Cahn, M. N. Cailleux, Dr Surowka (86 [105], 26/60); Bobigny, Hôpital Avicenne (hem), P. Casassus ()*; Bordeaux, CHU Hôpital de Bordeaux Enfants, Y. Perel ()*; Brest, Centre Hospitalier, C. Berthou (40 [51], 0/40); Caen, Hôpital Cote de Nacre (peds hem onco), P. Boutard (3 [3], 0/3); Caen, Centre Hospitalier Régional, CIC 251, O. Reman (22 [25], 0/22); Caen, Centre Régional François Baclesse, A. M. Peny (19 [20], 0/19); Clermont Ferrand, Hotel Dieu (peds), F. Démeocq ()*; Clermont Ferrand, Centre Jean Perrin, CIC 273, J.-O. Bay, (76 [76], 14/62); Clichy, Hôpital Beaujon, J. Brière ()*; Colmar, Hôpital civil, B. Audhuy (8 [8], 0/8); Corbeil Essonne, Hôpital Gilles de Corbeil, A. Devidas (11 [11], 0/11); Créteil, Hôpital H. Mondor, CIC 252, C. Cordonnier, M. Kuentz (60 [62], 22/38); Dijon, Hôpital d'Enfants, D. Caillot (70 [91], 0/70); Dunkerque, Centre Hospitalier (hem), M. Wetterwald (9 [9], 0/9); Grenoble, Centre Hospitalier (ads, allo peds), CIC 270, J. J. Sotto, F. Garban, P. Drillat (50 [55], 13/37); Grenoble, Centre Hospitalier (auto peds), D. Plantaz, M. Bost (8 [8], 0/8); Lille, Hôpital Claude Huriez, CIC 277, F. Bauters, J. P. Jouet (112 [126], 43/69); Lille, Hôpital Jeanne de Flandre, Dr. Nelken (2 [2], 0/2); Lille, Centre Oscar Lambret (onco), Dr Depadt, Dr Defachelles (20 [20], 0/20); Lille, Centre Hospitalier Saint Vincent, N. Cambier (15 [15], 0/15); Limoges, Centre Hospitalier Dupuytren (ads), CIC 977, D. Bordessoule, P. Turlure (37 [43], 0/37); Limoges, Centre Hospitalier Dupuytren (peds), Prof De Lumley (2 [2], 0/2); Lyon Sud (Pierre Benite), Centre Hospitalier, B. Coiffier (124 [135], 0/124); Lyon, Hôpital Edouard Herriot, CIC 671, D. Fiere, E. Archimbaud, A. Belhabri, M. Michallet (61 [68], 30/31); Lyon, Centre Léon Bérard, CIC 241, P. Biron, T. Philip (66 [78], 0/66); Lyon, Hôpital Debrousse, N. Philippe, G. Souillet, Y. Bertrand (24 [27], 24/0); Marseille, Inst. Paoli-Calmettes, CIC 230, D. Blaise (196 [283], 19/177); Marseille, Hôpital d'Enfants de la Timone (onco), CIC 301, C. Coze, J. L. Bernard (9 [10], 0/9); Marseille, Hôpital d'Enfants de la Timone, G. Michel (16 [18], 16/0); Meaux, Centre Hospitalier de Meaux, C. Soussain (6 [8], 0/6); Metz, Thionville Hôpital Notre-Dame de Bon-Secours (hem), V. Dorvaux (18 [24], 0/18); Montpellier, CHU de Montpellier Hôpital Arnaud de Villeneuve, F. Bernard (11 [11], 2/9); Montpellier, Centre Rég De Lutte contre de Cancer, M. Fabbro, J- B. Dubois (13 [13], 0/13); Montpellier, CHR Lapeyronie, J. F. Rossi (95 [100], 18/77); Mulhouse, Hôpital du Hasenrain, Ph. Hénon, Dr Becker (15 [16], 0/15); Nantes, Hotel Dieu, CIC 253, J. L. Harousseau, N. Milpied (146 [203], 30/116); Nice, Hôpital de Cimiez, CIC 523, J. G. Fuzibet, J. P. Cassuto, N. Gratecos (52 [55], 15/37); Nice, Fondation Lenval (peds), Dr Soler, Dr. De Ricaud (1 patient received transplant in Marseille (1 [1], 0/1); Nice, Centre Antoine Lacassagne, A. Thyss (20 [21], 0/20); Paris, Hôpital Européen GP, J. M. Andrieu, C. Le Maignan (7 [10], 0/7); Paris, Hôpital d'Instruction des Armées Percy, Clamart, T. de Revel, G. Nedellec (28 [31], 3/25); Paris, Hôpital Cochin, J - P. Levy, F. Dreyfus (36 [36], 0/36); Paris, Hôpital Necker des enfants malades, CIC 210, A. Fischer (39 [43], 36/3); Paris, Hôpital St Antoine, CIC 213, C. Gorin, L. Fouillard (48 [59], 8/40); Paris, Hôpital St Louis (auto), CIC 805, G. Gisselbrecht (58 [61], 0/58); Paris, Hôpital St Louis (allo), CIC 207, E. Gluckman (87 [92], 86/1); Paris, Hôpital St Louis (peds), CIC 748, A. Baruchel, M-F. Auclerc (3 [3], 0/3); Paris, Hôpital St Louis (auto immuno-Haem), CIC 969, J-C. Brouet, B. Royer, J- P. Fermand (57 [58], 0/57); Paris, Hôpital St Louis (auto-leuk), CIC 960, H. Dombret, L. Degos, P. Rousselot (14 [16], 0/14); Paris, Hôpital Pitié Salpétière (hem), CIC 262, J-P. Vernant, V. Leblond (91 [100], 42/49); Paris, Hôpital D'enfants Armand-Trousseau, G. Leverger, A. Auvrignon (10 [10], 0/10); Paris, Hôpital Tenon, J. P. Lotz (32 [57], 0/32); Paris, Hôpital Robert Debré, P. Rohrlich, E. Vilmer (22 [22], 21/1); Paris, Hôpital Necker (ads), CIC 160, B. Varet, C. Bélanger, A. Veil (63 [66], 28/35); Paris, Hôtel Dieu (hem), CIC 222, J-P. Marie, B. Rio (50 [57], 13/37); Paris, Hotel Dieu (