title: Stored red blood cell viability is maintained after treatment with a second-generation S-303 pathogen inactivation process.
abstract: BACKGROUND
  Transfusion-transmitted infections and immunologic effects of viable residual lymphocytes remain a concern in red blood cell (RBC) transfusion. Pathogen reduction technologies for RBC components are under development to further improve transfusion safety. S-303 is a frangible anchor-linker-effector with labile alkylating activity and a robust pathogen reduction profile. This study characterized the viability of RBCs prepared with a second-generation S-303 process and stored for 35 days.
  
  
  METHODS
  This was a two-center, single-blind randomized, controlled, crossover study in 27 healthy subjects. S-303 (test) or control RBCs were prepared in random sequence and stored for 35 days, at which time an aliquot of radiolabeled RBCs was transfused. The 24-hour recovery, RBC life span, and in vitro metabolic and viability variables were analyzed.
  
  
  RESULTS
  The mean 24-hour RBC recovery and hemolysis of test RBCs were similar to control RBCs and were consistent with the Food and Drug Administration (FDA) guidance for RBC viability. The mean differences in life span and median life span (T(50) ) of circulating test RBCs were 13.7 and 6.8 days, while the mean difference in the area under the curve of surviving RBCs was 1.38%, in favor of control RBCs. There were no clinically relevant abnormal laboratory values after the infusion of test RBCs. All crossmatch assays of autologous S-303 RBCs were nonreactive.
  
  
  CONCLUSIONS
  RBCs prepared using the S-303 pathogen inactivation process were physiologically and metabolically suitable for transfusion after 35 days of storage, met the FDA guidance criteria for 24-hour recovery, and did not induce antibody formation.
authors.affiliation: Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio 45267-0055, USA. jose.cancelas@uc.edu
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cancelas
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Dumont
authors.forename: Neeta
authors.initials: N
authors.lastname: Rugg
authors.forename: Zbigniew M
authors.initials: ZM
authors.lastname: Szczepiorkowski
authors.forename: Louis
authors.initials: L
authors.lastname: Herschel
authors.forename: Alan
authors.initials: A
authors.lastname: Siegel
authors.forename: P Gayle
authors.initials: PG
authors.lastname: Pratt
authors.forename: D Nicole
authors.initials: DN
authors.lastname: Worsham
authors.forename: Anne
authors.initials: A
authors.lastname: Erickson
authors.forename: Meisa
authors.initials: M
authors.lastname: Propst
authors.forename: Anne
authors.initials: A
authors.lastname: North
authors.forename: Claire D
authors.initials: CD
authors.lastname: Sherman
authors.forename: Nina A
authors.initials: NA
authors.lastname: Mufti
authors.forename: William F
authors.initials: WF
authors.lastname: Reed
authors.forename: Laurence
authors.initials: L
authors.lastname: Corash
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001793:Blood Preservation; D002470:Cell Survival; D018592:Cross-Over Studies; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D016037:Single-Blind Method
chemical_list: C506266:(N,N-bis(2-chloroethyl))-2-aminoethyl-3-((acridin-9-yl)amino)propionate; D000166:Acridines; D009588:Nitrogen Mustard Compounds