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      Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years

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          Abstract

          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.

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          Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

          Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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            Chimeric antigen receptor T cells for sustained remissions in leukemia.

            Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells. A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab. Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL. CTL019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (Funded by Novartis and others; CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.).
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              Chimeric Antigen Receptor Therapy.

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                Author and article information

                Contributors
                jakob.passweg@usb.ch
                Journal
                Bone Marrow Transplant
                Bone Marrow Transplant
                Bone Marrow Transplantation
                Nature Publishing Group UK (London )
                0268-3369
                1476-5365
                23 February 2021
                23 February 2021
                2021
                : 56
                : 7
                : 1651-1664
                Affiliations
                [1 ]GRID grid.410567.1, EBMT Activity Survey Office, Division of Hematology, Department of Medicine, , University Hospital, ; Basel, Switzerland
                [2 ]GRID grid.418443.e, ISNI 0000 0004 0598 4440, Institut Paoli Calmettes Comprehensive Cancer Center & Inserm CBT-1409, , Centre d’Investigations Cliniques en Biothérapies, ; Marseille, France
                [3 ]GRID grid.13339.3b, ISNI 0000000113287408, Department of Hematology, Oncology and Internal Medicine, , Medical University of Warsaw, ; Warsaw, Poland
                [4 ]GRID grid.411251.2, ISNI 0000 0004 1767 647X, Department of Hematology, , Hospital Universitario de la Princesa, ; Madrid, Spain
                [5 ]GRID grid.7727.5, ISNI 0000 0001 2190 5763, Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, , University of Regensburg, ; Regensburg, Germany
                [6 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Laboratory of Hematology, Department of Laboratory Medicine, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [7 ]GRID grid.73221.35, ISNI 0000 0004 1767 8416, Servicio de Hematologia y Hemoterapia, , Hospital Universitario Puerta de Hierro, ; Madrid, Spain
                [8 ]GRID grid.491869.b, ISNI 0000 0000 8778 9382, Klinik für Hämatologie und Stammzelltransplantation, , HELIOS Klinikum Berlin-Buch, ; Berlin, Germany
                [9 ]GRID grid.15496.3f, Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, , Vita-Salute San Raffaele University, ; Milan, Italy
                [10 ]GRID grid.10419.3d, ISNI 0000000089452978, Willem-Alexander Children’s Hospital, Department of Pediatrics, , Leiden University Medical Centre Leiden, ; Leiden, The Netherlands
                [11 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Department of Hematology, Hospital Saint Antoine, INSERM UMRs938, , Sorbonne University, ; Paris, France
                [12 ]BMT Unit, Department of Hematology, Hospital St. Louis, Paris, France
                [13 ]GRID grid.31410.37, ISNI 0000 0000 9422 8284, Department of Haematology, , Sheffield Teaching Hospitals NHS Foundation Trust, ; Sheffield, UK
                [14 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, CHU de Lille, INSERM U1286, Infinite, , Univ Lille, ; Lille, France
                [15 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Department of Stem Cell Transplantation, , University Hospital Eppendorf, ; Hamburg, Germany
                Author information
                http://orcid.org/0000-0002-6554-483X
                http://orcid.org/0000-0002-3755-4889
                http://orcid.org/0000-0003-3858-8180
                http://orcid.org/0000-0002-8189-5779
                http://orcid.org/0000-0002-6117-5328
                http://orcid.org/0000-0003-4524-8782
                Article
                1227
                10.1038/s41409-021-01227-8
                8263343
                33623153
                12c33400-7eb7-4fd4-bf7d-8b68e3909d36
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 December 2020
                : 12 January 2021
                : 25 January 2021
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2021

                Transplantation
                haematological cancer,leukaemia
                Transplantation
                haematological cancer, leukaemia

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