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      Strong Association between Respiratory Viral Infection Early after Hematopoietic Stem Cell Transplantation and the Development of Life-Threatening Acute and Chronic Alloimmune Lung Syndromes

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          Abstract

          Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with ideopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS ( P <.0001). This was true for all viruses tested. In multivariate analysis, allo-LS was the only predictor for higher mortality ( P = .04). Paradoxically, prolonged administration of immunosuppressive agents because of acute graft-versus-host disease had a protective effect on the development of allo-LS ( P = .004). We hypothesize that early infection of the respiratory tract with a common cold virus makes the lungs a target for alloimmunity.

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          Most cited references 34

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          Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center.

          Community respiratory viruses (CRVs) have been recognized as a potential cause of pneumonia and death among hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancies. We reviewed the Microbiology Laboratory records dated from July 1, 2000, to June 30, 2002, to identify patients who had respiratory specimens positive for influenza, parainfluenza, respiratory syncytial virus, or picornavirus. We identified 343 infections among patients with underlying hematologic malignancies and HSCT. We collected data on type of disease, age, sex, type of infection, neutrophil and lymphocyte counts, therapy, and outcome. Influenza, parainfluenza, and respiratory syncytial virus accounted for most cases and were approximately equal in frequency. Most infections occurred predominantly among recipients of allogeneic transplants. Infection progressed to pneumonia in 119 patients (35%) and occurred with similar frequency for the 3 viruses. Patients at greatest risk for developing pneumonia included those with leukemia, those aged more than 65 years, and those with severe neutropenia or lymphopenia. Lack of respiratory syncytial virus-directed antiviral therapy (p=0.025) and age (p=0.042) were associated with development of respiratory syncytial virus pneumonia, and an absolute lymphocyte count
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            Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome.

            Parainfluenza virus (PIV) infections may be significant causes of morbidity and mortality in patients undergoing stem cell transplantation, but data regarding their impact on transplant-related mortality is limited. This study sought to determine the risk factors of PIV acquisition and progression to lower respiratory tract infection, their impact on transplant-related mortality, and the effectiveness of antiviral therapy. A total of 3577 recipients of hematopoietic stem cell transplantation (HSCT) between 1990 and 1999 were studied. PIV infections occurred in 253 patients (7.1%); 78% of these infections were community acquired. Multivariable analysis identified the receipt of an unrelated transplant as the only risk factor for PIV acquisition; the dose of corticosteroids at the time of PIV infection acquisition was the primary factor associated with the development of PIV-3 pneumonia, both among allogeneic and autologous HSCT recipients. Both PIV-3 upper respiratory infection and pneumonia were associated with overall mortality. Pulmonary copathogens were isolated from 29 patients (53%) with pneumonia. Mortality was highly influenced by the presence of copathogens and the need for mechanical ventilation. Aerosolized ribavirin with or without intravenous immunoglobulin did not appear to alter mortality from PIV-3 pneumonia, nor did such therapy decrease the duration of viral shedding from the nasopharynx among patients with pneumonia. Corticosteroid administration thus drives the development of PIV pneumonia in a dose-dependent fashion, even among autologous HSCT recipients. Both upper and lower tract PIV infections are predictors of mortality after HSCT. Currently available antiviral therapy appears to be inadequate in reducing viral shedding or mortality once pneumonia is established. (Blood. 2001;98:573-578)
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              Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

              Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.
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                Author and article information

                Contributors
                Journal
                Biol Blood Marrow Transplant
                Biol. Blood Marrow Transplant
                Biology of Blood and Marrow Transplantation
                Published by Elsevier Inc.
                1083-8791
                1523-6536
                6 January 2010
                June 2010
                6 January 2010
                : 16
                : 6
                : 782-791
                Affiliations
                [1 ]Department of Pediatric Hematology/Immunology and Bone Marrow Transplantation, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands
                [2 ]Department of Virology, Eijkman-Winkler Center, University Medical Center Utrecht, Utrecht, The Netherlands
                [3 ]Laboratory of Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, The Netherlands
                [4 ]Department of Paediatric Respiratory Medicine, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands
                Author notes
                []Correspondence and reprint requests: A. B. Versluys, University Medical Center Utrecht/Wilhelmina Children's Hospital, Lundlaan 6, 3584 EA Postbus 85090, 3508 AB, Utrecht, The Netherlands. a.b.versluys@ 123456umcutrecht.nl
                S1083-8791(09)01166-5
                10.1016/j.bbmt.2009.12.534
                7110441
                20060053
                Copyright © 2010 Published by Elsevier Inc.

                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.

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