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Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion-associated graft-versus-host disease?

Authors

  • Loren D. Fast,

    Corresponding author
    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
      Loren D. Fast, PhD, Department of Medicine (Research), Division of Hematology/Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903; e-mail: Loren_Fast@brown.edu.
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  • Martha Nevola,

    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
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  • Jennifer Tavares,

    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
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  • Heather L. Reddy,

    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
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  • Ray P. Goodrich,

    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
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  • Susanne Marschner

    1. From the Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island; and TerumoBCT Biotechnologies, LLC, Lakewood, Colorado.
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  • This study was supported by research funding from CaridianBCT Biotechnologies to LDF. CaridianBCT Biotechnologies is a recipient of a grant from the US Army Medical Research and Materiel Command, Telemedicine and Advanced Technology Research Center, under Contract W81XWH-09-2-0100.

Loren D. Fast, PhD, Department of Medicine (Research), Division of Hematology/Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903; e-mail: Loren_Fast@brown.edu.

Abstract

BACKGROUND: Exposure of blood products to gamma irradiation is currently the standard of care in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with the use of gamma irradiators are driving efforts to develop alternatives. Pathogen reduction methods were initially developed to reduce the risk of microbial transmission by blood components. Through modifications of nucleic acids, these technologies interfere with the replication of both pathogens and white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of products containing red blood cells are less well established than those for platelets and plasma.

STUDY DESIGN AND METHODS: In this study, the in vitro and in vivo function of WBCs present in whole blood after exposure to riboflavin plus ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained from untreated or gamma-irradiated blood by measuring proliferation, cytokine production, activation, and antigen presentation and xenogeneic (X-)GVHD responses in an in vivo mouse model.

RESULTS: In vitro studies demonstrated that treatment of whole blood with Rb-UV was as effective as gamma irradiation in preventing WBC proliferation, but was more effective in preventing antigen presentation, cytokine production, and T-cell activation. Consistent with in vitro findings, treatment with Rb-UV was as effective as gamma irradiation in preventing X-GVHD, a mouse model for TA-GVHD.

CONCLUSION: The ability to effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation into components, provides the transfusion medicine community with a potential alternative to gamma irradiation.

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