This Open Access edition of the European Society for Blood and Marrow Transplantation (EBMT) handbook addresses the latest developments and innovations in hematopoietic stem cell transplantation and ...cellular therapy. Consisting of 93 chapters, it has been written by 175 leading experts in the field. Discussing all types of stem cell and bone marrow transplantation, including haplo-identical stem cell and cord blood transplantation, it also covers the indications for transplantation, the management of early and late complications as well as the new and rapidly evolving field of cellular therapies. This book provides an unparalleled description of current practices to enhance readers’ knowledge and practice skills.
Numbers of Hematopoietic cell transplantation (HCT) in Europe and collaborating countries continues to rise with 48,512 HCT in 43,581 patients, comprising of 19,798 (41%) allogeneic and 28,714 (59%) ...autologous, reported by 700 centers in 51 countries during 2019. Main indications were myeloid malignancies 10,764 (25%), lymphoid malignancies 27,895 (64%), and nonmalignant disorders 3173 (7%). A marked growth in CAR-T cellular therapies from 151 in 2017 to 1134 patients in 2019 is observed. This year's analyses focus on changes over 30 years. Since the first survey in 1990 where 143 centers reported 4234 HCT, the number has increased to 700 centers and 48,512 HCT. Transplants were reported in 20 countries in 1990, and 51, 30 years later. More than 800,000 HCT in 715,000 patients were reported overall. Next to the massive expansion of HCT technology, most notable developments include the success of unrelated donor and haploidentical HCT, an increase followed by decrease in the number of cord blood transplants, use of reduced intensity HCT in older patients, and the phenomenal rise in cellular therapy. This annual report of the European Society for Blood and Marrow Transplantation (EBMT) reflects current activity and highlights important trends vital for health care planning.
Allogeneic hematopoietic stem-cell transplantation is a potentially curative therapy for various hematologic diseases. An essential component of this procedure is the pre-transplant conditioning ...regimen, which should facilitate engraftment and reduce or eliminate tumor cells. The recognition of the substantial association of a graft-versus- tumor effect and the high toxicity of the commonly used conditioning regimen led to the introduction of more differentiated intensity strategies, with the aim of making hematopoietic stem-cell transplantation less toxic and safer, and thus more applicable to broader populations such as older or unfit patients. In general, prospective and retrospective studies suggest a correlation between increasing intensity and nonrelapse mortality and an inverse correlation with relapse incidence. In this review, we will summarize traditional and updated definitions for conditioning intensity strategies and the landscape of comparative prospective and retrospective studies, which may help to find the balance between the risk of non-relapse mortality and relapse. We will try to underscore the caveats regarding these definitions and analyses, by missing complex differences between intensity and toxicity as well as the broad influences of other factors in the transplantation procedure. We will summarize evidence regarding several confounders which may influence decisions when selecting the intensity of the conditioning regimen for any given patient, according to the individual risk of relapse and non-relapse mortality.
Currently available data on chimeric antigen receptor (CAR)-T cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated multiple myeloma (MM) patients. The CAR-T field in ...MM is rapidly evolving with >50 currently ongoing clinical trials across all phases, different CAR-T design, or targets. Most of the CAR-T trials are performed in China and the United States, while European centers organize or participate in only a small fraction of current clinical investigations. Autologous CAR-T cell therapy against B cell maturation antigen shows the best evidence of efficacy so far but main issues remain to be addressed: duration of response, longer follow-up, prolonged cytopenia, patients who may benefit the most such as those with extramedullary disease, outcome prediction, and the integration of CAR-T cell therapy within the MM treatment paradigm. Other promising targets are, i.a.,: CD38, SLAMF7/CS1, or GPRC5D. Although no product has been approved to date, cost and production time for autologous products are expected to be the main obstacles for broad use, for which reason allogeneic CAR-T cells are currently explored. However, the inherent risk of graft-versus-host disease requires additional modification which still need to be validated. This review aims to present the current status of CAR-T cell therapy in MM with an overview on current targets, designs, and stages of CAR-T cell development. Main challenges to CAR-T cell therapy will be highlighted as well as strategies to structurally improve the CAR-T cell product, and thereby its efficacy and safety. The need for comparability of the most promising therapies will be emphasized to balance risks and benefits in an evidence-based but personalized approach to further improve outcome of patients with MM.
Hematopoietic-cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants performed in Europe and associated countries continues ...to rise with 47,468 HCT in 42,901 patients 19,630 allogeneic (41%) and 27,838 autologous (59%) reported by 701 centers in 50 countries in 2018. Main indications were myeloid malignancies 10,679 (25%; 97% allogeneic), lymphoid malignancies 27,318 (64%; 20% allogeneic), solid tumors 1625 (4%; 2.9% allogeneic), and nonmalignant disorders 3063 (7%; 81% allogeneic). This year's analysis focuses on cellular therapies with the marked growth in CAR T-cell therapies from 151 in 2017 to 301 patients reported in 2018. Other cellular therapy numbers show less significant changes. Important trends in HCT include a 49% increase in allogeneic HCT for chronic phase CML (although transplant numbers remain low) and a 24% increase in aplastic anemia. In autologous HCT, there is an ongoing increase in autoimmune diseases (by 19%), predominantly due to activity in multiple sclerosis. This annual report reflects current activity and highlights important trends, useful for health care planning.
Antilymphocyte globulin (ATG) added to the conditioning regimen before allogeneic hematopoietic stem-cell transplantation resulted in a lower rate of chronic graft-versus-host disease at 2 years than ...the rate without ATG (32% vs. 68%), with no apparent increased risk of relapse.
Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic stem-cell transplantation that results in later illness and death and a reduction in quality of life.
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Risk factors for chronic GVHD are the use of peripheral blood as a source of stem cells, a history of acute GVHD, and the use of donated stem cells with high numbers of T cells.
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In a meta-analysis, the Stem Cell Trialists’ Collaborative Group reported an incidence of extensive chronic GVHD of 47% after peripheral-blood stem-cell transplantation from an HLA-identical sibling.
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In 2012, more than 70% of the stem-cell transplantations performed in . . .
Chronic graft-versus-host disease (cGVHD) is one of the major causes of late mortality after allogenic hematopoietic stem cell transplantation. Moderate-to-severe cGVHD is associated with poor ...health-related quality of life and substantial disease burden. While corticosteroids with or without calcineurin inhibitors comprise the first-line treatment option, the prognosis for patients with steroid-refractory cGVHD (SR-cGVHD) remains poor. The mechanisms underlying steroid resistance are unclear, and there are no standard second-line treatment guidelines for patients with SR-cGVHD. In this review, we provide an overview on current treatment options of cGVHD and use a series of theoretical case studies to elucidate the rationale of choices of second- and third-line treatment options for patients with SR-cGVHD based on individual patient profiles.
Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to ...rise with 45,418 HCT in 41,100 patients (17,155 allogeneic (42%) and 23,945 autologous (58%) reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
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