1.
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
Abstract
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.
2.
A randomized, controlled Phase III trial of therapeutic plasma exchange with fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light compared to untreated FFP in thrombotic thrombocytopenic purpura
Mintz PD, Neff A, MacKenzie M, Goodnough LT, Hillyer C, Kessler C, McCrae K, Menitove JE, Skikne BS, Damon L, et al
Transfusion. 2006;46((10):):1693-704.
Abstract
BACKGROUND Photochemical treatment of fresh-frozen plasma (FFP) with amotosalen and ultraviolet (UV) A light (PCT FFP) results in inactivation of a broad spectrum of pathogens while retaining coagulation factor activity, antithrombotic proteins, and von Willebrand factor-cleaving protease (VWF-CP) activity. STUDY DESIGN AND METHODS A randomized, controlled, double-blind Phase III trial was conducted with PCT FFP or control FFP for therapeutic plasma exchange (TPE) in patients with thrombotic thrombocytopenic purpura (TTP). Owing to the rarity of this diagnosis, the trial was not powered to demonstrate small differences between treatment groups. Patients were treated with study FFP for a maximum of 35 days until remission was achieved (for a maximum of 30 daily study TPEs with no remission) plus an additional 5 days after remission. RESULTS Among the 35 patients treated, the primary endpoint, remission within 30 days, was achieved by 14 of 17 (82%) PCT patients and 16 of 18 (89%) control patients (p = 0. 658) The 90 percent confidence interval for treatment difference in remission rate for test - control was (-0. 291 to 0. 163). Time to remission, relapse rates, time to relapse, total volume and number of FFP units exchanged, and number of study TPEs were not significantly different between groups. Improvement in VWF-CP and inhibitors was similar for both groups. The overall safety profile of PCT FFP was similar to control FFP. No antibodies to amotosalen neoantigens were detected. CONCLUSION The comparable results between treatment groups observed from this small trial suggest that TPE with PCT FFP was safe and effective for treatment of TTP.
3.
VWF cleaving protease activity and inhibitors in patients with thrombotic thrombocytopenic purpura (TTP) treated with INTERCEPT FFP vs. conventional FFP: results of a phase III trial
Conlan MGC, Corash L, Lin JS, Mintz PD, Neff AT, Malcolm MR, Hillyer CD, Goodnough LT,, et al.,
Vox Sanguinis. 2005;89((S2):):40. Abstract No. 5P-046.
4.
S-303 pathogen inactivated red blood cells in patients with hemoglobinopathies participating in chronic transfusion programs: preliminary safety and efficacy results
Conlan MGC, Vichinsky E, Snyder E, Goodnough LT, Labotka R, Eder A, Sloan SR, Minniti C, Lin J, Corash L
Vox Sanguinis. 2005;89((Suppl 1):):121. Abstract No. T-PA-076.
5.
vWF cleaving protease activity and inhibitors in patients with thrombotic thrombocytopenic purpura (TTP) treated with INTERCEPT FFP vs. conventional FFP: results of a phase III trial
Conlan MG, Corash L, Lin J, Mintz PD, Neff AT, MacKenzie M, Hillyer CD, Goodnough LT,, et al.,
Transfusion. 2005;45((s3):):30A.. Abstract No. S92-040G.
6.
Antibody formation to S-303-treated RBCs in the setting of chronic RBC transfusion
Conlan MG, Stassinopoulos A, Garratty G, Wages D, Corash L, Wood L,, et al.,
Blood. 2004;104((11):):112a-113a.. Abstract No. 382.