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

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.

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

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 (R(2)=0.54); this connection was even stronger for allogeneic HSCT (R(2)=0.67). These data illustrate status and trends for HSCT in Europe. They provide a rational basis for planning and patient counseling.

The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies.

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.

Why are there regional differences in stem cell transplantation activity? An EBMT analysis.

Differences in the number of hematopoietic SCTs (HSCT), in transplant rates, in indications and in techniques between countries have been reported. They were attributed mainly to differences in the economic situation of the countries or to differences in prevalences of the disease. On the basis of the results of the annual activity survey on HSCT of the European Blood and Marrow Transplantation (EBMT), we have analyzed the factors associated with differences between more than 600 teams participating from more than 40 countries over a time span of 15 years. The results show a more complex situation. The gross national income per capita, number of transplant teams per 10 million inhabitants or per 10,000 km2, team size and team experience all impact on transplant activity. Furthermore, hitherto unknown factors must add to the decisions to perform or not to perform HSCT. These data illustrate that more research is needed to understand the mechanism of HSCT activity and to enable health-care agencies to provide the necessary infrastructure.

The EBMT activity survey 2006 on hematopoietic stem cell transplantation: focus on the use of cord blood products.

This report describes the hematopoietic stem cell transplantation (HSCT) activity in Europe in 2006 by indication, donor type and stem cell source. It illustrates differences compared to previous years and concentrates on the use of cord blood transplants. In 2006, there were 25 050 first HSCT, 9661 allogeneic (39%), 15 389 autologous (61%) and 3690 additional re- or multiple transplants reported from 605 centers in 43 participating countries. Main indications were leukemias (7963 (32%; 85% allogeneic)); lymphomas (14 169 (56%; 89% autologous)); solid tumors (1564 (6%; 95% autologous)); non-malignant disorders (1242 (5%; 90% allogeneic)) and non-classified 'others' (112 (1%)). There was an increase in allogeneic HSCT of 9% when compared to 2005, while autologous HSCT numbers remained similar. There were 544 allogeneic cord blood HSCT, which corresponds to 5% of all allogeneic HSCT. The majority, 67%, were used for patients with leukemia. The highest percentage of cord blood transplants, 27%, was seen for inherited disorders of metabolism. No autologous cord blood transplants were reported. The highest increase in allogeneic HSCT was observed for AML, which comprises 31% of all allogeneic HSCT. Numbers of autologous HSCT remained similar in most main indications. This data provide an update of the current HSCT experience in Europe.

Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: focus on increasing use of unrelated donors.

This EBMT activity report documents the haematopoietic stem cell transplantation (HSCT) activity in Europe in 2005. It provides numbers of HSCT by indication, donor type and stem cell source, lists the new practice of planned double transplants with allogeneic after autologous HSCT and concentrates on the increasing role of unrelated transplants over the last years. In 2005, there were 24,168 first HSCT, 8890 allogeneic (37%), 15,278 autologous (63%) and 3773 additional re- or multiple transplants reported from 597 centres in 43 participating countries. Main indications were leukaemias (7404 (31%; 82% allogeneic)); lymphomas (13,825 (57%; 89% autologous)); solid tumours (1655 (7%; 92% autologous)) and non-malignant disorders (1131 (5%; 93% allogeneic)). A total of 671 planned allogeneic after autologous HSCT were reported; the majority for myeloma (52%), lymphoma (28%) and acute myeloid leukaemia (11%). Compared to 2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT remained constant. The most noticeable increase was in unrelated HSCT, which comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed for leukaemias and in countries with high income according to World Bank criteria. These data illustrate the current experience in Europe and form the basis for patient counselling and decisions making at health care institutions.

EBMT activity survey 2004 and changes in disease indication over the past 15 years.

This fifteenth annual European Group for Blood and Marrow Transplantation activity report lists the transplant activity in Europe in 2004 and documents the changes in indication over the past 15 years. In 2004, there were 22 216 first hematopoetic stem cells (HSCT), 7407 allogeneic (33%), 14 809 autologous (67%) and 4378 additional re- or multiple transplants reported from 592 centres in 38 European and five affiliated countries. Main indications were leukemias (7045 (32%; 78% allogeneic)); lymphomas (12 310 (55%; 94% autologous)); solid tumors (1759 (8%; 93% autologous)) and nonmalignant disorders (1015 (5%; 92% allogeneic)). In comparison, 145 teams from 20 countries performed 4234 HSCT (2137 allogeneic, 50%; 2097 autologous, 50%) in 1990. The overall increase was accompanied by major changes. Stem cell source changed from bone marrow to peripheral blood. More than one-third of allogeneic HSCT are now from unrelated donors. Reduced intensity conditioning is employed for one-third of allogeneic HSCT. Leukemias for allogeneic and lymphoproliferative disorders for autologous HSCT continue to increase. The decline in HSCT for chronic myeloid leukemia appears to level off for the first time since 1999. These data are informative for patient counselling and decision making for health care professionals.

Nucleolar morphology and rDNA in situ hybridisation in monocytes.

The aim of this study was to correlate morphological changes of nucleoli of non-proliferating monocytes to their functional activity, since nucleolar morphology is currently considered as a diagnostic marker for cell proliferation. Monocytes from healthy donors were fractionated by current counterflow centrifugation and kept in culture for 6 days. Cells were stimulated by the addition of 200 units/ml interferon gamma (IFN gamma). Under this stimulus the monocytes show no proliferation but a strongly augmented expression of type I Fc IgG receptor, human leucocyte antigen DR, human leucocyte antigen DP and human leucocyte antigen DQ. Morphological changes after stimulation included the appearance of multinucleated cells, typical signs of the activation of rRNA synthesis indicated by an increase in nucleolar size, and changes in nucleolar structure such as the appearance of reticulate and compact nucleoli. The number of nucleolus organiser regions (NORs) visualised by in situ hybridisation was compared with the position and number of nucleoli visualised by silver staining in interphase cells. In comparison with control cultures, activated monocytes show a distinct increase in the number of those NORs that take part in the formation of nucleoli. Our results show that, in non-proliferating activated monocytes, the morphology of nucleoli and the increase of NOR activity are similar to those in proliferating cells. NOR activation is therefore an indicator for cellular activity, but is not necessarily correlated with proliferation.