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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.
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2.
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.
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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.
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4.
Platelets photochemically treated with amotosalen HCl and ultraviolet A light correct prolonged bleeding times in patients with thrombocytopenia
Slichter SJ, Raife TJ, Davis K, Rheinschmidt M, Buchholz DH, Corash L, Conlan MG
Transfusion. 2006;46((5):):731-40.
Abstract
BACKGROUND Photochemical treatment (PCT) with amotosalen HCl with ultraviolet A illumination inactivates pathogens and white blood cells in platelet (PLT) concentrates. STUDY DESIGN AND METHODS In a Phase II crossover study, 32 patients with thrombocytopenia received one transfusion of PCT and/or one transfusion of untreated (reference) apheresis PLTs. Hemostatic efficacy was assessed with the cutaneous template bleeding time and clinical observations. RESULTS Paired bleeding time data for PCT and reference transfusions were available for 10 patients. Mean pretransfusion bleeding times were 29. 2 +/- 1. 6 minutes in the PCT group and 28. 7 +/- 2. 5 minutes in the reference group. After transfusion of a dose of PLTs of at least 6. 0 x 10(11), mean 1-hour posttransfusion template bleeding times corrected to 19. 3 +/- 9. 5 minutes in the PCT group and 14. 3 +/- 6. 5 minutes in the reference group (p = 0. 25). In 29 patients receiving paired PCT and reference transfusions, mean 1-hour posttransfusion PLT count increments were 41. 9 x 10(9) +/- 20. 8 x 10(9) and 52. 3 x 10(9) +/- 18. 3 x 10(9) per L for PCT and reference, respectively (p = 0. 007), and mean 1-hour posttransfusion PLT corrected count increments (CCIs) were 10. 4 x 10(3) +/- 4. 9 x 10(3) and 13. 6 x 10(3) +/- 4. 3 x 10(3) for PCT and reference, respectively (p < 0. 001). The time to next PLT transfusion was 2. 9 +/- 1. 2 days after PCT transfusions versus 3. 4 +/- 1. 3 days after reference transfusions (p = 0. 18). Clinical hemostasis was not significantly different after PCT and reference transfusions. CONCLUSION PCT PLTs provided correction of prolonged bleeding times and transfusion intervals not significantly different than reference PLTs despite significantly lower PLT count increments and CCIs.
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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.
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Platelet dose consistency and its effect on the number of platelet transfusions for support of thrombocytopenia: an analysis of the SPRINT trial of platelets photochemically treated with amotosalen HCl and ultraviolet A light
Murphy S, Snyder E, Cable R, Slichter SJ, Strauss RG, McCullough J, Lin JS, Corash L, Conlan MG, SPRINT Study Group
Transfusion. 2006;46((1):):24-33.
Abstract
BACKGROUND The SPRINT trial examined efficacy and safety of photochemically treated (PCT) platelets (PLTs). PCT PLTs were equivalent to untreated (control) PLTs for prevention of bleeding. Transfused PLT dose and corrected count increments (CIs), however, were lower and transfusion intervals were shorter for PCT PLTs, resulting in more PCT than control transfusions. PLT dose was analyzed to determine the impact of the number of PLTs transfused on transfusion requirements. STUDY DESIGN AND METHODS Transfusion response was compared for patients with all doses of >or=3. 0 x 10(11) and the complementary subset of patients with any dose of fewer than 3. 0 x 10(11). Analyses included comparison of bleeding, number of PLT and red blood cell (RBC) transfusions, transfusion intervals, and CIs between PCT and control groups within each PLT dose subset. RESULTS Mean PLT dose per transfusion in the PCT group was lower than in the control group (3. 7 x 10(11) vs. 4. 0 x 10(11); p<0. 001). More PCT patients received PLT doses of fewer than 3. 0 x 10(11) (n=190) than control patients (n=118; p<0. 01). Comparisons of patients receiving comparable PLT doses showed no significant differences between PCT and control groups for bleeding or number of PLT or RBC transfusions; however, transfusion intervals and CIs were significantly better for the control group. CONCLUSIONS When patients were supported with comparable doses of PCT or conventional PLTs, the mean number of PLT transfusions was similar. Lower CIs and shorter transfusion intervals for PCT PLTs suggest that some PLT injury may occur during PCT. This injury does not result in a detectable increase in bleeding, however.
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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.
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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.
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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.
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10.
Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial
Snyder E, McCullough J, Slichter SJ, Strauss RG, Lopez-Plaza I, Lin JS, Corash L, Conlan MG, SPRINT Study Group
Transfusion. 2005;45((12):):1864-75.
Abstract
BACKGROUND A photochemical treatment (PCT) method utilizing a novel psoralen, amotosalen HCl, with ultraviolet A illumination has been developed to inactivate viruses, bacteria, protozoa, and white blood cells in platelet (PLT) concentrates. A randomized, controlled, double-blind, Phase III trial (SPRINT) evaluated hemostatic efficacy and safety of PCT apheresis PLTs compared to untreated conventional (control) apheresis PLTs in 645 thrombocytopenic oncology patients requiring PLT transfusion support. Hemostatic equivalency was demonstrated. The proportion of patients with Grade 2 bleeding was not inferior for PCT PLTs. STUDY DESIGN AND METHODS To further assess the safety of PCT PLTs, the adverse event (AE) profile of PCT PLTs transfused in the SPRINT trial is reported. Safety assessments included transfusion reactions, AEs, and deaths in patients treated with PCT or control PLTs in the SPRINT trial. RESULTS A total of 4719 study PLT transfusions were given (2678 PCT and 2041 control). Transfusion reactions were significantly fewer following transfusion of PCT than control PLTs (3. 0% vs. 4. 1%; p = 0. 02). Overall AEs (99. 7% PCT vs. 98. 2% control), Grade 3 or 4 AEs (79% PCT vs. 79% control), thrombotic AEs (3. 8% PCT vs. 3. 7% control), and deaths (3. 5% PCT vs. 5. 2% control) were comparable between treatment groups. Minor hemorrhagic AEs (petechiae [39% PCT vs. 29% control; p < 0. 01] and fecal occult blood [33% PCT vs. 25% control; p = 0. 03]) and skin rashes (56% PCT vs. 42% control; p < 0. 001) were significantly more frequent in the PCT group. CONCLUSION The overall safety profile of PCT PLTs was comparable to untreated PLTs.