title: Red blood cell concentrates treated with the amustaline (S-303) pathogen reduction system and stored for 35 days retain post-transfusion viability: results of a two-centre study.
abstract: OBJECTIVE
  Pathogen reduction technology using amustaline (S-303) was developed to reduce the risk of transfusion-transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second-generation process and stored for 35 days was evaluated in two different blood centres.
  
  
  METHODS
  In a single-blind, randomized, controlled, two-period crossover study (n = 42 healthy subjects), amustaline-treated (Test) or Control RBCs were prepared in random sequence and stored for 35 days. On day 35, an aliquot of51Cr/99mTc radiolabeled RBCs was transfused. In a subgroup of 26 evaluable subjects, 24-h RBC post-transfusion recovery, mean life span, median life span (T50) and life span area under the curve (AUC) were analysed.
  
  
  RESULTS
  The mean 24-h post-transfusion recovery of Test and Control RBCs was comparable (83·2 ± 5·2 and 84·9 ± 5·9%, respectively; P = 0·06) and consistent with the US Food and Drug Administration (FDA) criteria for acceptable RBC viability. There were differences in the T50between Test and Control RBCs (33·5 and 39·7 days, respectively; P < 0·001), however, these were within published reference ranges of 28-35 days. The AUC (per cent surviving × days) for Test and Control RBCs was similar (22·6 and 23·1 per cent surviving cells × days, respectively; P > 0·05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events.
  
  
  CONCLUSIONS
  RBCs prepared using amustaline pathogen reduction meet the FDA criteria for post-transfusion recovery and are metabolically and physiologically appropriate for transfusion following 35 days of storage.
authors.affiliation: Hoxworth Blood Center, Cincinnati, OH, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Cancelas
authors.affiliation: BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Gottschall
authors.affiliation: Hoxworth Blood Center, Cincinnati, OH, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rugg
authors.affiliation: BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Graminske
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Schott
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: North
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Mufti
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Erickson
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rico
authors.affiliation: Cerus Corporation, Concord, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Corash
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001793:Blood Preservation; D002470:Cell Survival / Q000187:drug effects; D002859:Chromium Isotopes / Q000737:chemistry; D018592:Cross-Over Studies; D004906:Erythrocyte Count; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006406:Hematoma / Q000209:etiology; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000494:pharmacology*; D012372:ROC Curve; D016037:Single-Blind Method; D013667:Technetium / Q000737:chemistry; D013997:Time Factors; D038301:Virus Inactivation / Q000187:drug effects; D055815:Young Adult
chemical_list: C506266:(N,N-bis(2-chloroethyl))-2-aminoethyl-3-((acridin-9-yl)amino)propionate; D000166:Acridines; D002859:Chromium Isotopes; D009588:Nitrogen Mustard Compounds; D013667:Technetium
keywords: S-303; amustaline; pathogen reduction; red blood cells; viability