Pandemic 2009 H1N1 Influenza in Patients with Hematopoietic Stem Cell Transplantation and Hematologic Malignancy: Single Center Experience
Bone Marrow Transplantation Unit, Ankara Oncology Education and Research Hospital, Ankara, Turkey.Oncology (Impact Factor: 2.42). 03/2011; 79(5-6):409-14. DOI: 10.1159/000320789
Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5-15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.
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ABSTRACT: Influenza viruses cause potentially fatal respiratory infections in stem cell transplant patients. Specific T cells provide long-lived host adaptive immunity to influenza viruses, and the potential for generating such cells for clinical use was investigated. The inactivated influenza vaccine (Fluvax) approved for human use was used as the antigen source. Monocyte-derived dendritic cells pulsed with Fluvax were used to stimulate autologous peripheral blood mononuclear cells (PBMC) on days 0 and 7. Cells were expanded with interleukin (IL)-2 from day 7 onwards. Cell numbers and phenotype were assessed on day 21. The presence of influenza virus-specific cells was assessed by cytokine production and proliferative responses following restimulation with influenza antigens. Over 21 days of culture, a mean fold increase of 26.3 in cell number was observed (n = 7). Cultures were predominantly effector and central memory CD4+ cells, and expressed a phenotype characteristic of activated antigen-specific cells capable of B-cell helper function. Cytotoxic CD4+ and CD8+ cells specific for influenza and a high percentage of CD4+ cells specific for each of three influenza viruses targeted by Fluvax (H1N1, H3N2 and Brisbane viruses) were generated. In addition, T cells expanded when restimulated with antigens derived from influenza viruses. We have demonstrated a clinically usable method for producing influenza virus-specific T cells that yield high numbers of highly reactive CD4+ cells suitable for adoptive immunotherapy. We propose that reconstructing host immunity through adoptive transfer of influenza virus-specific T cells will reduce the frequency of influenza-related deaths in the period of severe immune suppression that follows stem cell transplantation.
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ABSTRACT: Before the advent of the influenza A(H1N1)pdm virus in 2009, the information available about the clinical manifestations and prognosis of influenza in immunosuppressed patients was scarce. With the 2009 pandemic, knowledge of the behavior, severity and importance of antiviral therapy for influenza A infection in immunocompromised hosts has increased considerably. The aim of the present manuscript is to review the main challenges of influenza in the most representative immunosuppressed populations such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with solid and hematological cancer and human immunodeficiency virus infected patients.
Article: Engelhard D, Mohty B, de la Camara R, Cordonnier C, Ljungman P. European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL-4, on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN. Transpl Infect Dis 2013; 15: 219-232[Show abstract] [Hide abstract]
ABSTRACT: Influenza may cause severe disease and mortality in leukemia patients and in hematopoietic stem cell transplantation recipients. The 4th European Conference of Infections in Leukemia (ECIL-4) has developed evidence-based guidelines for prevention and management of influenza infections in these patients. Real-time reverse-transcription polymerase chain reaction is the diagnostic test of choice, as it is the most sensitive and specific test for influenza. The risks for severe influenza and fatal outcome include lymphopenia, older age, influenza soon after transplantation or chemotherapy, steroid treatment, and lack of early antiviral therapy. Neuraminidase inhibitors (oral oseltamivir or inhalation of zanamivir) are currently the most effective therapeutic agents for influenza. Main preventive measures include annual vaccination of patients, household contacts, and hospital staff. This review summarizes ECIL-4's main recommendations.
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