title: Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion-associated graft-versus-host disease?
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island 02903, USA. Loren_Fast@brown.edu
authors.forename: Loren D
authors.initials: LD
authors.lastname: Fast
authors.forename: Martha
authors.initials: M
authors.lastname: Nevola
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tavares
authors.forename: Heather L
authors.initials: HL
authors.lastname: Reddy
authors.forename: Ray P
authors.initials: RP
authors.lastname: Goodrich
authors.forename: Susanne
authors.initials: S
authors.lastname: Marschner
mesh_terms: D000818:Animals; D001769:Blood / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D012256:Riboflavin / Q000494:pharmacology* / Q000627:therapeutic use; D065227:Transfusion Reaction; D019172:Transplantation Conditioning / Q000379:methods*; D014183:Transplantation, Heterologous; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D012256:Riboflavin