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      Managing hematological cancer patients during the COVID-19 pandemic: An ESMO-EHA Interdisciplinary Expert Consensus

      research-article
      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , ∗∗
      ESMO Open
      Published by Elsevier Ltd on behalf of European Society for Medical Oncology.
      COVID-19, hematological malignancies, consensus manuscript
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          Abstract

          Background

          The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies, raising questions about the optimal care of this patient group.

          Methods

          This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of hematological malignancies in the Covid-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the Covid-19 diagnosis, treatment, and mitigation strategies to specific-HM management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance.

          Results and Conclusion

          The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

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          Most cited references112

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

            Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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              Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

              Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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                Author and article information

                Journal
                ESMO Open
                ESMO Open
                ESMO Open
                Published by Elsevier Ltd on behalf of European Society for Medical Oncology.
                2059-7029
                28 January 2022
                28 January 2022
                : 100403
                Affiliations
                [1 ]Institute of Experimental Cancer Research, Department of Internal Medicine III, University Hospital Ulm
                [2 ]Department of Medicine III at LMU Hospital, Munich, Germany
                [3 ]Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain
                [4 ]MBChB, MD, FRCP, FRCPath, FMedSci, Professor of Haemato-oncology, Centre for Haematology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, United Kingdom
                [5 ]Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy
                [6 ]Service d’Hématologie Oncologie, Centre Hospitalier de Versailles, Le Chesnay, 78150, France ; UVSQ, Inserm, CESP, 94805, Villejuif, France
                [7 ]Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Berlin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
                [8 ]University of Milan & Hematology Division, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
                [9 ]Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele – Milan, Italy
                [10 ]Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
                [11 ]Consultant Haematologist & Hon Associate Professor, UCLH Centre for Waldenström and Neurohaematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
                [12 ]Department of Radiation Oncology, University of Muenster, Germany
                [13 ]Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
                [14 ]Strategic Research Program on Chronic Lymphocytic Leukemia and Laboratory of B Cell Neoplasia, Division of Molecular Oncology, Università Vita-Salute San Raffaele, and IRCCS Ospedale San Raffaele, Milano, Italy
                [15 ]Department Of Hematology, Portuguese Institute of Oncology, Lisbon, Portugal
                [16 ]Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
                [17 ]Department of Hematooncology University Hospital Ostrava, Department of Hematooncology, Faculty of Medicine, University of Ostrava
                [18 ]Clinical Director - Haematology, Haemostasis, Palliative Care, Cellular Pathology Guy's and St Thomas' NHS Foundation Trust , London, United Kingdom
                [19 ]Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
                [20 ]Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
                [21 ]Université de Paris, APHP, Hôpital Saint-Louis, Centre d’Investigations Cliniques, INSERM CIC 1427, Paris, France
                [22 ]MD, Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
                [23 ]Hematology department, University hospital hotel-dieu, place ricordeau, 44093 Nantes, France
                [24 ]Hematology Division, Basel University Hospital, Basel Switzerland
                [25 ]Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
                [26 ]Département médico universitaire d'hématologie et immunologie, France Intergroupe des Leucémies Myéloïdes Chroniques (Fi-LMC), Hôpital Saint-Louis, Paris, France
                [27 ]MD, PhD, Clinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
                [28 ]Department of Hematology, Medical University of Lodz, Lodz, Poland
                [29 ]Clínica Universidad de Navarra (CUN), Centro de Investigación Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), CIBERONC, 31008 Pamplona, Spain
                [30 ]MDS Unit, Hematology, DMSC, AOUC, University Of Florence, Firenze, Italy
                [31 ]Hematology Department, Hospital Univesitario y Politecnico La Fe, Valencia, Spain; CIBERONC, IS Carlos III, Madrid, Spain
                [32 ]Erasmus MC Cancer Institute, Dept. of Hematolog, Rotterdam, the Netherlands
                [33 ]Department of Hematology and Medical Oncology, University Hospital Jena, Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany
                [34 ]Munich Clinic Schwabing, Academic Teaching Hospital, Ludwig-Maximilian University, Munich, Germany
                [35 ]Scientific and Medical Division, ESMO European Society for Medical Oncology, Lugano, Switzerland
                [36 ]Department of Medicine and Surgery, University of Insubria, Varese, Italy
                Author notes
                []Corresponding authors: Christian Buske, MD Institute of Experimental Cancer Research University Hospital Ulm, Germany Albert-Einstein-Allee 23, 89081 Ulm, Germany
                [∗∗ ]Corresponding authors: Francesco Passamonti, MD, Department of Medicine and Surgery, University of Insubria, Varese, Ospedale di Circolo, Varese, Viale Borri, 57, Varese, Italy
                Article
                S2059-7029(22)00024-2 100403
                10.1016/j.esmoop.2022.100403
                8795783
                35272130
                8aa95981-cc98-4fb3-9c56-e72bfa125d9f
                © 2022 Published by Elsevier Ltd on behalf of European Society for Medical Oncology.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 20 November 2021
                : 13 January 2022
                : 18 January 2022
                Categories
                Original Research

                covid-19,hematological malignancies,consensus manuscript

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