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Transmission of cytomegalovirus (CMV) infection by leukoreduced blood products not tested for CMV antibodies: a single-center prospective study in high-risk patients undergoing allogeneic hematopoietic stem cell transplantation (CME)

Authors

  • Thomas Thiele,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • William Krüger,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Kathrin Zimmermann,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Till Ittermann,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Antje Wessel,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Ivo Steinmetz,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Gottfried Dölken,

    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • Andreas Greinacher

    Corresponding author
    1. From the Institut für Immunologie und Transfusionsmedizin; Klinik für Innere Medizin C, Haematologie und Onkologie; Friedrich Löffler Institut für Medizinische Mikrobiologie; and Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
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  • TT and AG designed the study. KZ and IS performed CMV assays; TI and AW performed statistical analyses and made the figures and tables; WK and GD treated the patients; TT, WK, GD, and AG analyzed results and wrote the manuscript; and all authors reviewed and approved the final version of the manuscript.

Andreas Greinacher, Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Sauerbruchstraße, 17489 Greifswald, Germany; e-mail: greinach@uni-greifswald.de.

Abstract

BACKGROUND: Measures to prevent transfusion-transmitted cytomegalovirus (TT-CMV) infection after hematopoietic stem cell transplantation (HSCT) include transfusion of CMV antibody–negative blood units and/or transfusion of leukoreduced cellular blood products. We assessed the incidence of TT-CMV in CMV-seronegative patients receiving CMV-seronegative HSC transplants, who were transfused with leukoreduced cellular blood products not tested for anti-CMV.

STUDY DESIGN AND METHODS: In a prospective observational study between 1999 and 2009, all HSCT patients received leukoreduced cellular blood products not tested for anti-CMV. Patients were screened for CMV serostatus and CMV-negative recipients of CMV-negative transplants were systematically monitored for TT-CMV clinically and by CMV nucleic acid testing. Anti-CMV antibodies (immunoglobulin [Ig]G and IgM) were assessed after three time intervals (Interval 1, study inclusion to Day +30 after HSCT; Interval 2, Day +30-Day +100; Interval 3, after Day +100).

RESULTS: Among 142 patients treated with allogeneic HSCT, 23 CMV-negative donor-patient pairs were identified. These 23 patients received 1847 blood products from 3180 donors. All patients remained negative for CMV DNA and none developed CMV-associated clinical complications. This results in a risk for TT-CMV per donor exposure of 0% (95% confidence interval, 0.0%-0.12%). However, 17 of 23 patients seroconverted for anti-CMV IgG, but none for anti-CMV IgM. CMV IgG seroconverters received significantly more transfusions per week than nonconverters.

CONCLUSION: The risk of TT-CMV is low in high-risk CMVneg/neg HSCT patients transfused with leukoreduced blood products not tested for anti-CMV. The cause of anti-CMV IgG seroconversion is most likely passive antibody transmission by blood products.

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