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Allogeneic bone marrow transplantation is a curative intervention for both neoplastic and non-malignant conditions. However, not all patients have an HLA-matched donor. Therefore, the development of an approach that expand the donor pool was of paramount relevance. The development of post-transplantation cyclophosphamide as graft versus host disease prophylaxis allows the safe use of haploidentical donors, solving the donor availability problem to the vast majority of patients in need. The present paper reviews the history of the development of haploidentical transplantation at Johns Hopkins University, from the bench to the bedside.

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Bone marrow transplantation (BMT) has evolved over the last 60 years from a pioneering treatment fraught with unknown factors and complications to a widely practiced standard of care that has saved the lives of countless individuals with malignant and non-malignant conditions. Over this period, transplanters in the UK have made a significant international contribution to the field through cutting edge clinical and laboratory research. Today, stem cell transplantation in the UK continues to advance through rigorous and innovative clinical trials which focus on improving outcome by reducing transplant toxicity and the risk of disease relapse. In this review, we start with a personal view of the early years of BMT in the UK, document the many seminal accomplishments in the field of BMT which took place in the UK, and end with a look towards the future of BMT, in the UK and worldwide., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The availability of hematopoietic cell transplantation as curative therapy for blood disorders has been dramatically improved through a better understanding of the human leukocyte antigen (HLA) barrier. Although a fully compatible unrelated donor is preferable, transplantation from donors with a limited degree of HLA mismatching is associated with acceptable outcomes in many cases. Research on the limits of HLA mismatching, and the features that define permissible HLA mismatches will continue to enable transplantation to be more broadly available to patients in need., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In 1985, Eugene Cronkite and his colleagues published, in Experimental Hematology, data indicating that five consecutive "transfusions" of large numbers of marrow cells significantly increase the number of donor-derived cells detected by day 10 of a spleen colony-forming assay, the most primitive hematopoietic cells detectable at that time, present in the host for as long as 2 months posttransfusion (Cronkite EP, Bullis JE, Brecher G. Marrow transfusions increase pluripotent stem cells in normal hosts. Exp Hematol 1985;13:802-805). These data provided the first evidence that donor hematopoietic stem cells (HSCs) may persist in vivo for some time in recipients when transfused and not transplanted, that is, not subjected to treatments that deplete their marrow niches of endogenous HSCs. The limited technology available at the time prevented Dr. Cronkite from pursuing this observation into the development of nonmyeloablated transplantation procedures, and his experiment, as well as the term bone marrow transfusion, has since been long forgotten. In recent years, the scientific need to clarify HSC functions in nonstressed hosts and the clinical need to develop transplantation procedures with levels of morbidity/mortality acceptable for curing inherited hematologic disorders have inspired the search for nonmyeloablative transplantation procedures, including methods that "outcompete" endogenous host HSCs such as those pioneered by Dr. Cronkite's experiments using high transfusion doses. This review describes the technical progress made since Dr. Cronkite's insightful work, which has finally found its path to the clinic., (Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

History of hematopoietic stem cell transplantations in Poland begins in early 1980s; the 1st bone marrow allotransplantation was performed in 1983 in the Central Clinical Hospital of the Military Medical Academy in Warsaw. Following years brought the 1st autologous stem cell transplantations. Ten years later, unrelated bone marrow transplantation was performed for the 1st time by the team of the Hematology and Blood and Marrow Transplantation Unit in Katowice. Since then, hematopoietic stem cell transplantation developed to be standard procedure and one of the most important therapies applied in leukemia treatment. The number of allotransplantations in Poland has grown significantly in the past 2 decades, which generated new needs and problems. In 2005, based on a new Transplant Law, a National Transplants Registry was created. Its main role is to collect data (registration of procedures and follow-up data) related to every transplantation case for stem cells and tissues as well as for organs. We present statistics concerning stem cell transplantations performed in Poland, as collected in the National Transplants Registry in the years 2006-2014. There are 18 centers transplanting hematopoietic stem cells in Poland. The total number of hematopoietic stem cell transplantations performed in 2006-2014 was 3,537, with allotransplantations from relatives accounted for 1,491 and from unrelated donors for 2,046. The main indication for allotransplantation in past years was acute leukemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Immunoglobulin light chain amyloidosis is the most common type of systemic amyloidosis. Hematopoietic stem cell transplantation (HCT) is an effective treatment option for AL however due to multi-organ involvement in this disease HCT is feasible in a minority of patients. To maximize the benefit and minimize toxicity it is of paramount importance to optimize the selection of patients for HCT. In this review we discuss evolution of HCT and its typical application to a case of AL amyloidosis., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) has been used as a part of cancer therapy for over half a decade. Beyond the necessity for donor-derived cells to reconstitute hematopoiesis after radiation and chemotherapy, immunologic reconstitution from allogeneic cells is important for the elimination of residual tumor cells. Natural killer (NK) cells are first among lymphocytes to reconstitute post-transplant and protect against cancer relapse. In this review, we provide a historical perspective on the role of NK cells in cancer control in the transplant setting and focus on current research aimed at improving NK cell responses for therapeutic benefit.

For over 50 y the association between hematopoietic chimerism and tolerance has been recognized. This originated with the brilliant observation by Dr. Ray Owen that freemartin cattle twins that shared a common placental blood supply were red blood cell chimeras, which led to the discovery that hematopoietic chimerism resulted in actively acquired tolerance. This was first confirmed in neonatal mice by Medawar et al. and subsequently in adult rodents. Fifty years later this concept has been successfully translated to solid organ transplant recipients in the clinic. The field is new, but cell-based therapies are being used with increasing frequency to induce tolerance and immunomodulation. The future is bright. This review focuses on chimerism and tolerance: past, present and prospects for the future.

The sixties have not only witnessed the start of the Dutch Society for Immunology (NvvI), but were also the flourishing beginning of the discipline of transplant immunology. The interest in immunology in the Netherlands had its start in the context of blood transfusions and not for instance in the field of infectious disease, as in many other countries. It began in the 1950-ties thanks to Joghem van Loghem at that time director of the Central Laboratory of Blood Transfusion in Amsterdam. The discoveries of these times have had major impact for transfusion medicine, hematopoietic stem cell transplantation and organ transplantation. In this review we will look back at some early highlights of Dutch transplant immunology and put them in the perspective of some recent developments., (Copyright © 2014 Elsevier B.V. All rights reserved.)

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

This year marked the occurrence of several important milestones in the treatment of acute leukemias. First, the standard 7 + 3 protocol for acute myeloid leukemia (AML) was developed 40 years ago, and with some adaptations, has stood the test of time. Second, the 1 millionth hematopoietic cell transplant was recorded this year. Stem cell transplant, the first reported by Dr E. Donnall Thomas in 1957, had been considered a rare procedure until about a decade ago. Today, it has become a proven and often life-saving therapy for patients with acute leukemia. Advances in the treatment of patients with AML continue to take place, many of which relate to an increased understanding of the clinical heterogeneity of known subtypes. Forty years ago, the regimen that has come to be known as 7+3 for acute myeloid leukemia (AML) was born [1,2]. Cytosine arabinoside, or arabinosylcytosine as it was then called, was given as a continuous intravenous infusion of 100 mg/m(2) for 7 days, and the anthracycline, daunorubicin, was administered at 45 mg/m(2) intravenously for 3 days. Sixteen patients were originally treated on this protocol, and 5 of 8 previously untreated and 2 of 8 previously treated patients achieved a complete response (CR). This regimen has withstood the test of time. Attempts to add or substitute other agents have not yielded superior results. The only major contemporary change is that a higher dose of daunorubicin is safe and has become the standard of care [3]., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Over the last 2 decades, there have been a number of changes in clinical practice that individually could affect the outcome of allogeneic hematopoietic cell transplantation (HCT), but until recently the collective impact of these changes was unknown. Accordingly, several groups asked the question of whether the outcome of allogeneic HCT has improved, and if so, why. Four large studies including a total of more than 10,000 patients have been performed and have reached very similar conclusions. Compared to transplants performed in the 1990s, the hazard ratio for nonrelapse mortality for transplants performed in the 2000s was roughly 0.5. This remarkable improvement was seen when the analyses were restricted to myeloablative transplants, to recipients of marrow rather than peripheral blood, or to transplants from matched siblings, and persisted after analyses were adjusted for patient risk. Likely explanations for this improvement include the avoidance of the most toxic preparative regimens, use of agents that spare hepatic and renal function, and improved methods for control of infections., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A retrospective review of the published literature identified several hundred adverse reactions (e.g. nausea, chills, cardiac arrhythmias, neurological symptoms and respiratory arrest) associated with the transplantation of stem cells cryopreserved with dimethyl sulfoxide. The occurrences of these are generally accepted as commonplace, as the majority of reactions are transient, whilst a few patients may require clinical treatment. This exploratory study is a collation of the historical data and the expectations for the notification of serious adverse reactions. Outline information is presented on the development of related European Directives, some technical aspects of dimethyl sulfoxide and the sequential stages of preservation and administration.

Hematopoietic stem cell transplantation (HSCT) has evolved over the last half century from experimental bone marrow transplantation for patients with incurable leukemia or bone marrow failure to standard of care for a broad range of patients with congenital or acquired disorders of the hematopoietic system or radio-, chemo- or immune-sensitive malignancies. More than 60,000 such transplants are currently carried out annually worldwide with increasing frequency. HSCT has always been closely linked to Dermatology from its very beginning through its main and most devastating complication graft-versus-host disease. Treatment complications of HSCT have provided a great deal of insight into basic mechanisms of immunology, clinical medicine and networking in general. It remains a challenge to turn this knowledge from the two disciplines into benefit for the future patients with disturbed immune function and skin diseases., (Copyright © 2012 S. Karger AG, Basel.)

Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone marrow environment, the biology of hematopoietic stem cells and histocompatibility. The development of this new discipline has allowed numerous groups working around the world to cure patients of diseases previously considered lethal. Together with the ever growing list of volunteer donors and umbilical cord blood banks, this has resulted in life saving therapy for thousands of patients yearly. We present an overview of the procedure from its cradle to the most novel applications, as well as the results of the HSC transplant program developed at our institution since 1989.

Purpose of Review: Systemic sclerosis (SSc) remains one of the last severe autoimmune disease with a poor prognosis and modest response to immunosuppressive therapy. Mortality in severe diffuse disease with internal organ involvement is elevated. Autologous hematopoietic transplantation (HSCT) has emerged in the last decade as a promising disease-modifying treatment., Recent Findings: In phase I/II trials, HSCT has demonstrated to induce impressive reversal of skin fibrosis, neoangiogenesis, improved functionality and quality of life, and stabilization of internal organ function. Treatment-related mortality was reduced over time by better pretransplant evaluation and by treating patients earlier in disease., Summary: Two out of three randomized trials of autologous HSCT for SSc have been concluded: the nonmyeloablative American Systemic Sclerosis Immune Suppression versus Transplant, and Autologous Stem cell Transplantation International Scleroderma. The myeloablative Scleroderma Cyclophosphamide versus Transplant instead is still recruiting patients. The soon expected results from these trials should clarify the role of autologous HSCT in the challenging management of severe SSc.

Introduction: Allogeneic hematopoietic stem cell transplantation (SCT) is the treatment of choice for many malignant hematological disorders. Following recent improvements in non-relapse-related mortality rates, relapse has become the commonest cause of treatment failure. Infusion of donor lymphocytes can potentially enhance immune-mediated antitumor activity and offers a salvage option for some patients. This paper reviews the current literature on the efficacy of this therapeutic strategy., Areas Covered: The biology of adoptive cellular therapy with allogeneic immune cells to treat relapse across a spectrum of diseases in both the full intensity and reduced intensity hematopoietic SCT settings is explored. The review discusses the current limitations of the approach and reviews several new experimental strategies which aim to segregate the desired graft-versus-tumor effect from the deleterious effects of more widespread graft-versus-host reactivity., Expert Opinion: Durable responses to DLI have been noted in chronic myeloid leukemia and responses have also been described in acute leukemia, multiple myeloma and chronic lymphoproliferative disorders. The new challenge in transplantation is to optimize DLI therapy in order to further improve patient outcomes.

Allogeneic hematopoietic stem cell transplantation represents a curative treatment approach for a large range of hematologic malignancies. Traditionally, high-dose radiochemotherapy as preparative regimen has been thought to be necessary for successful allogeneic stem cell transplantation. However, high-dose conditioning often results in considerable medullary and extramedullary toxicity, contributing to high rates of treatment-related mortality. This limits the use of this procedure to patients below 60 years of age without significant comorbidities. Since the peak incidence of most hematological malignancies is beyond the 5th decade of life, the majority of patients are not eligible for high-dose treatment. During the last 15 years, several dose-reduced or even non-myeloablative conditioning regimens have been developed, offering a curative treatment option for these patients. This review summarizes the history of reduced-intensity conditioning (RIC) transplantations, depicts the differences among regimens, highlights significant patient factors, and describes the impact on selected hematological malignancies., (Copyright © 2011 S. Karger AG, Basel.)

The year 2009 marked the fiftieth anniversary of the first successful allogeneic haematopoietic stem cell transplant (HSCT). The field of HSCT has pioneered some of the most exciting areas of research today. HSCT was the original stem cell therapy, the first cancer immune therapy and the earliest example of individualized cancer therapy. In this Timeline article we review the history of the development of HSCT and major advances made in the past 50 years. We highlight accomplishments made by researchers who continue to strive to improve outcomes for patients and increase the availability of this potentially life-saving therapy for patients with otherwise incurable malignancies.

In October 1988, the world's first umbilical cord blood transplant (UCBT) was performed. Despite considerable skepticism initially by both scientists and clinical specialists in the field, umbilical cord blood (UCB) has now become one of the most commonly used sources of hematopoietic stem cells (HSCs) for allogeneic transplantation. Today, an estimated 600,000 UCB units have been banked and 20,000 UCB units have been distributed worldwide for both adults and children with life-threatening malignant and nonmalignant diseases. During this first generation of UCBT, substantial advances have been made resulting in better outcomes for our patients. UCB serves as an extraordinary example of translational medicine at its best, where clinical problems compel scientists to move basic discoveries into novel therapeutic approaches. This chapter briefly summarizes the highpoints of the history of UCBT with speculations as to what the next generation of research promises to discover., ((c) 2010 Elsevier Inc. All rights reserved.)

Almost 30 years have passed since the first successful hematopoietic stem cell transplantation in thalassemia and that first patient is now a healthy young adult with a completely normal life. Since that time, more than 3000 such transplants have been performed worldwide. This review provides a brief history of hematopoietic stem cell transplantation in thalassemia and reassesses current clinical results with the objective to provide outcome predictions based on modern transplant technologies. The role of hematopoietic stem cell transplantation in the oral chelation era and implications for possible closure in the approach to future gene therapy will also be discussed.

The field of cord blood transplantation has come a long way since the first transplant more than 20 years ago. Advancements in the field will require continuing efforts to better understand hematopoietic stem and progenitor cell function and engraftment. Cautious optimism is inherent in the potential relevance and applicability of nonhematopoietic stem and progenitor cell types found in cord blood, and induced pluripotent stem cells generated from cord blood cells. Rigorous investigations and close interactions between scientific and clinical investigators are required to translate human in vitro and animal in vivo findings into clinical utility., ((c) 2010 Elsevier Inc. All rights reserved.)

Objectives: To provide an overview of the history of hematopoietic stem cell transplantation (HSCT)., Data Sources: Research studies, book chapters, websites, and articles., Conclusion: The history of HSCT begins in the late 1950s. Although many treatment strategies have evolved, the basic concepts of transplantation remain the same., Implications for Nursing Practice: An understanding of the history of HSCT and transplant nursing practice are important to broaden the knowledge of nurses caring for transplant patients.

Despite many clinical advances in allogeneic hematopoietic cell transplantation (HCT), the one factor that is consistently required to apply HCT to a wide variety of diseases is the successful donation and the safe transport and administration of viable donor cells to the HCT recipient. Since 1987, the National Marrow Donor Program (NMDP) has maintained a registry of volunteer HCT donors for those patients who lack a suitable related donor, facilitated the donor search, and managed the collection and transportation of donor cells to transplant centers for use in increasingly complex therapies. The NMDP has collected data on marrow and peripheral blood stem cell (PBSC) donations as well as additional donations of lymphocytes, whole blood, or platelets. These additional donations are provided for a variety of reasons, including treating post-transplant complications such as graft failure or relapsed disease, supporting immune reconstitution or providing transfusion support. For donor safety, rates of placement of central venous catheters for collecting PBSC are monitored. Data have also been collected on rare events that may affect the integrity of the HCT product (e.g., graft clotting or leaks from the transport bag). Quality assurance and review of these donation processes is an essential component of the transplantation approach. Data from the broad NMDP experience further illuminate factors surrounding the donation process and product integrity.

In the 20 years since the National Marrow Donor Program (NMDP) facilitated the first unrelated donor transplant, the organization has grown to include almost 7 million donors, and has facilitated over 30,000 transplants on 6 continents. This remarkable accomplishment has been facilitated by the efforts of over 600 employees, and an extensive international network including 171 transplant centers, 73 donor centers, 24 cord blood banks, 97 bone marrow collection centers, 91 apheresis centers, 26 HLA typing laboratories, and 26 Cooperative Registries. In this article, we review the history of the NMDP, and cite the major trends in patient demographics, graft sources, and conditioning regimens over the last 20 years.

The National Marrow Donor Program (NMDP) has facilitated unrelated donor hematopoietic cell transplants for more than 20 years. In this time period, there have been many changes in clinical practice, including improvements in HLA typing and supportive care, and changes in the source of stem cells. Availability of banked unrelated donor cord blood (incorporated into the NMDP registry in 2000) as a source of stem cells has become an important option for children with leukemia, offering the advantages of immediate availability for children with high-risk disease, the need for a lesser degree of HLA match, and expanding access for those with infrequent HLA haplotypes. Overall survival (OS) in children with acute leukemia transplanted with unrelated donor bone marrow (BM) is markedly better in more recent years, largely attributable to less treatment-related mortality (TRM). Within this cohort, 2-year survival was markedly better for patients with acute lymphoblastic leukemia (ALL) in first complete response (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease (33%). Similar findings are observed with patients with AML, suggesting earlier referral to bone marrow transplant (BMT) is optimal for survival. Notably, this improvement over time was not observed in unmodified peripheral blood stem cell (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell source for children.

Advances in stem cell research over the past few decades have coincided with large increases in haemopoietic stem cell transplantation (HSCT) using either bone marrow, peripheral blood or cord blood-derived stem cells. Alongside this growth has come an increase in the role played by regulatory bodies, both governmental and professional, to ensure that those undertaking such procedures do so in a manner so as to minimize the risk to patients. Interestingly, government legislation encompasses not only cellular therapies, but also the use of tissues and organs, as many of the processes and procurement procedures involved are similar. In this review, we analyse the trends in HSCT, describe the development and impact of legislation within Europe on this practice and outline the vital role played by the UK blood services in providing robust and high-quality HSCT services.

Autologous hematopoietic stem cell transplantation (HSCT) has a long tradition in Europe. Initially developed as a tool to restore rapid remission or chronic phase in patients with advanced leukemia without a sibling donor, it evolved over the last three decades to be used as a standard tool in patients with malignancies that are responsive to high-dose chemoradiotherapy. Autologous HSCTs are the standard of care for defined patients with lymphoid malignancies and for certain solid tumors of childhood. They continue to be evaluated in acute myeloid leukemia and are being investigated in phase II and III studies for defined severe autoimmune disorders. More than 15,000 such procedures, mainly peripheral blood stem cell transplants, are performed annually in Europe, which corresponds to double the number of allogeneic HSCTs. These numbers emphasize the important role of this type of therapy at its current stage.

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.

In the second half of the XX century, the transplant of hemopoietic progenitors ceased to be a desperate treatment with a high incidence of complications implying a high mortality, and became a curative treatment for thousands of patients with hematological neoplasias and other diseases. Since then understanding of the hemopoietic stem cells has increased, peripheral blood has replaced bone marrow as a source of progenitors, cord blood has been established as a viable source of progenitors and the realisation of unrelated transplants is a reality for many patients. The improvement of conditioning regimes and the introduction of new non-myeloablative treatments have reduced relapses. The new diagnostic techniques and the new anti-microbial treatments have reduced infectious complications and their mortality. There has been an advance in knowledge in determining minimal residual disease and the anti-tumour effect of the lymphocytes of the donor, which has made it possible to widen the indications. Besides, new understanding of the immunobiology of the transplant has, on the one hand, improved the options for controlling one of the principal complications, the graft-versus-host disease, and, on the other, a better use is made of the immunotherapeutic effect of the transplant.