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      Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors

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          Abstract

          Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55′668 deaths in 114′491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980–2001) to cohort 2 (2002–2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of “unknown origin”.

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          Reduced mortality after allogeneic hematopoietic-cell transplantation.

          Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation. We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation. In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).
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            European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia.

            Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient's risk factors for resistant bacteria and for a complicated clinical course. An 'escalation' approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A 'de-escalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72-96 h should be based on the patient's clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance.
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              One million haemopoietic stem-cell transplants: a retrospective observational study.

              The transplantation of cells, tissues, and organs has been recognised by WHO as an important medical task for its member states; however, information about how to best organise transplantation is scarce. We aimed to document the activity worldwide from the beginning of transplantation and search for region adapted indications and associations between transplant rates and macroeconomics.
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                Author and article information

                Contributors
                jstyczynski@cm.umk.pl
                Journal
                Bone Marrow Transplant
                Bone Marrow Transplant
                Bone Marrow Transplantation
                Nature Publishing Group UK (London )
                0268-3369
                1476-5365
                27 August 2019
                27 August 2019
                2020
                : 55
                : 1
                : 126-136
                Affiliations
                [1 ]ISNI 0000 0001 0943 6490, GRID grid.5374.5, Pediatric Hematology and Oncology, Collegium Medicum, , Nicolaus Copernicus University Torun, ; Bydgoszcz, Poland
                [2 ]Policlinico G.B. Rossi, Verona, Italy
                [3 ]GRID grid.476306.0, EBMT Data Office, ; Leiden, The Netherlands
                [4 ]ISNI 0000 0001 2300 0941, GRID grid.6530.0, Università di Roma “Tor Vergata”, ; Roma, Italy
                [5 ]ISNI 0000 0001 2151 3065, GRID grid.5606.5, Division of Infectious Diseases, , University of Genoa (DISSAL) and Ospedale Policlinico San Martino, ; Genoa, Italy
                [6 ]ISNI 0000 0001 2205 0971, GRID grid.22254.33, Medical University, ; Poznań, Poland
                [7 ]ISNI 0000 0001 2292 1474, GRID grid.412116.1, Hôpital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP) and Paris-Est-Créteil University, ; Creteil, France
                [8 ]Karolinska University Hospital, and Karolinska Institutet Stockholm, Stockholm, Sweden
                [9 ]ISNI 0000 0001 2221 2926, GRID grid.17788.31, Hadassah University Hospital, ; Jerusalem, Israel
                [10 ]ISNI 0000 0004 1767 647X, GRID grid.411251.2, Hospital de la Princesa, ; Madrid, Spain
                [11 ]GRID grid.410567.1, EBMT Activity Survey Office, Hematology, Department of Medicine, , University Hospital, ; Basel, Switzerland
                [12 ]ISNI 0000 0004 0578 8220, GRID grid.411088.4, Universitätsklinikum Frankfurt, Goethe-Universität, ; Frankfurt am Main, Germany
                [13 ]ISNI 0000000113287408, GRID grid.13339.3b, Department of Hematology, Oncology and Internal Medicine, , Medical University of Warsaw, ; Warsaw, Poland
                [14 ]GRID grid.15496.3f, Università Vita-Salute San Raffaele, ; Milan, Italy
                [15 ]ISNI 0000 0004 1767 8416, GRID grid.73221.35, Hospital Universitario Puerta de Hierro Majadahonda, ; Madrid, Spain
                [16 ]Hematology Unit, G. Gaslini Children’s Institute, Genova, Italy
                [17 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Haematology, , University Medical Centre, ; Utrecht, The Netherlands
                [18 ]ISNI 0000000089452978, GRID grid.10419.3d, Leiden University Hospital, ; Leiden, The Netherlands
                [19 ]ISNI 0000 0000 9244 0345, GRID grid.416353.6, Department of Haemato-oncology, , St Bartholomew’s Hospital, Barts Health NHS Trust, ; London, UK
                [20 ]ISNI 0000 0001 2107 2845, GRID grid.413795.d, Chaim Sheba Medical Center, ; Tel-Hashomer, Israel
                [21 ]ISNI 0000 0000 9422 8284, GRID grid.31410.37, Sheffield Teaching Hospitals NHS Foundation Trust, ; Sheffield, UK
                [22 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Department of Stem Cell Transplantation, , University Hospital Eppendorf, ; Hamburg, Germany
                [23 ]ISNI 0000 0004 1937 1100, GRID grid.412370.3, Department of Hematology, , Hospital Saint Antoine, ; Paris, France
                [24 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Hematology, Medical Faculty, , University of Basel, ; Basel, Switzerland
                Author information
                http://orcid.org/0000-0002-8281-3245
                http://orcid.org/0000-0002-8698-9547
                http://orcid.org/0000-0002-8189-5779
                http://orcid.org/0000-0003-3858-8180
                Article
                624
                10.1038/s41409-019-0624-z
                6957465
                31455899
                4ef858b5-3941-4f50-98f0-2824873cc307
                © The Author(s) 2019

                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
                : 22 July 2018
                : 2 April 2019
                : 28 May 2019
                Categories
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                © Springer Nature Limited 2020

                Transplantation
                epidemiology,risk factors
                Transplantation
                epidemiology, risk factors

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