Amustaline-glutathione pathogen-reduced red blood cell concentrates for transfusion-dependent thalassaemia
Aydinok Y, Piga A, Origa R, Mufti N, Erickson A, North A, Waldhaus K, Ernst C, Lin JS, Huang N, et al
British journal of haematology. 2019
Transfusion-dependent thalassaemia (TDT) requires red blood cell concentrates (RBCC) to prevent complications of anaemia, but carries risk of infection. Pathogen reduction of RBCC offers potential to reduce infectious risk. We evaluated the efficacy and safety of pathogen-reduced (PR) Amustaline-Glutathione (A-GSH) RBCC for TDT. Patients were randomized to a blinded 2-period crossover treatment sequence for six transfusions over 8-10 months with Control and A-GSH-RBCC. The efficacy outcome utilized non-inferiority analysis with 90% power to detect a 15% difference in transfused haemoglobin (Hb), and the safety outcome was the incidence of antibodies to A-GSH-PR-RBCC. By intent to treat (80 patients), 12.5 +/- 1.9 RBCC were transfused in each period. Storage durations of A-GSH and C-RBCC were similar (8.9 days). Mean A-GSH-RBCC transfused Hb (g/kg/day) was not inferior to Control (0.113 +/- 0.04 vs. 0.111 +/- 0.04, P = 0.373, paired t-test). The upper bound of the one-sided 95% confidence interval for the treatment difference from the mixed effects model was 0.005 g/kg/day, within a non-inferiority margin of 0.017 g/kg/day. A-GSH-RBCC mean pre-transfusion Hb levels declined by 6.0 g/l. No antibodies to A-GSH-RBCC were detected, and there were no differences in adverse events. A-GSH-RBCCs offer potential to reduce infectious risk in TDT with a tolerable safety profile.
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
Cancelas JA, Gottschall JL, Rugg N, Graminske S, Schott MA, North A, Huang N, Mufti N, Erickson A, Rico S, et al
Vox Sanguinis. 2017;112((3):):210-218
BACKGROUND AND OBJECTIVES 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. MATERIALS AND 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 of 51 Cr/99m Tc 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 T50 between 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 x days) for Test and Control RBCs was similar (22.6 and 23.1 per cent surviving cells x days, respectively; P > 0.05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events. CONCLUSION 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.
Clinical safety and efficacy of red blood cell Components treated with the s-303 pathogen inactivation system a randomized controlled double-blind phase 3 study in patients requiring transfusion support of acute anemia
Brixner V, Kiessling AH, Madlener K, Leibacher J, Mueller MM, Geisen C, Henschler R, North A, Huang N, Mufti N, et al
Vox Sanguinis. 2015;109((Suppl. 1)):28.. Abstract No. 3C-S10-04.
Red blood cells treated with the S-303 system for pathogen inactivation demonstrate in vitro characteristics suitable for transfusion: phase III clinical trial in cardiac surgery patients
Brixner V, Leibacher J, Pfeiffer H-U, Muller MM, Geisen C, Henschler R, Janetzko K, Heldke S, Huang N, Ernst C, et al
Vox Sanguinis. 2015;109((Suppl. 1)):185.. Abstract No. P-298.
Clinical safety and efficacy of red blood cell components treated with the second generation s-303 pathogen and leukocyte inactivation system – a randomized controlled double-blind phase 3 study in patients requiring transfusion support of acute anemia
Brixner V, Kiessling AH, Madlener K, Leibacher J, Muller M, Geisen C, Henschler R, North A, Huang N, Mufti N, et al
Transfusion Medicine and Hemotherapy. 2015;42((Suppl. 1)):4.. Abstract no. FV-02-1.
A multi-centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion
Lozano M, Knutson F, Tardivel R, Cid J, Maymo RM, Lof H, Roddie H, Pelly J, Docherty A, Sherman C, et al
British Journal of Haematology. 2011;153((3):):393-401.
Bacteria in platelet components (PC) may result in transfusion-related sepsis (TRS). Pathogen inactivation of PC with amotosalen (A-PC) can abrogate the risk of TRS and hence facilitate storage to 7 d. A randomized, controlled, double-blinded trial to evaluate the efficacy and safety of A-PC stored for 6-7 d was conducted. Patients were randomized to receive one transfusion of conventional PC (C-PC) or A-PC stored for 6-7 d. The primary endpoint was the 1 h corrected count increment (CCI) with an acceptable inferiority of 30%. Secondary endpoints included 1- and 24-h count increment (CI), 24-h CCI, time to next PC transfusion, red blood cell (RBC) use, bleeding and adverse events. 101 and 100 patients received A-PC or C-PC respectively. The ratio of 1-h CCI (A-PC:C-PC) was 0·87 (95% confidence interval: 0·73, 1·03) demonstrating non-inferiority (P = 0·007), with respective mean 1-h CCIs of 8163 and 9383; mean 1-h CI was not significantly different. Post-transfusion bleeding and RBC use were not significantly different (P = 0·44, P = 0·82 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2·2 vs. 2·3 d, P = 0·72). Storage of A-PCs for 6-7 d had no impact on platelet efficacy.
Frequency of prophylactic transfusion failure: a novel outcome to evaluate platelet components stored more than 5 days
Lozano M, Knutson F, Tardivel R, Cid J, Maymó R, Löf H, Roddie H, Lin L, Corash L, Prowse C
Transfusion. 2010;50((Suppl 2):):25A-26A.. Abstract No. S54-030D.
Comprehensive evaluation of a new process for S-303 pathogen-inactivation of red blood cells
Cancelas JA, Rugg N, Dumont LJ, Szczepiorkowski ZM, Siegel A, Erickson A, Propst M, North AK, Mufti N, Corash L
Transfusion. 2010;50((Suppl 2):):9A-10A.. Abstract No. S15-010C.
Serious pulmonary adverse events and acute lung injury following repeated platelet transfusions
Corash L, Eiden J, Lin S
Transfusion. 2008;48((S2):):28A.. Abstract No. S73-030F.
Acute lung injury in patients receiving repeated platelet transfusions
Corash L, Lin JS, Eiden J
Vox Sanguinis. 2008;95((Suppl 1):):300-301.. Abstract No. P-662.