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. 2020 Oct;60(10):2389-2398.
doi: 10.1111/trf.15965. Epub 2020 Jul 21.

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

Christof Geisen  1 , Anne North  2 , Lisa Becker  1 , Veronika Brixner  1 , Melissa von Goetz  2 , Laurence Corash  2 , Richard J Benjamin  2 , Nina Mufti  2 , Erhard Seifried  1
Affiliations

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

Christof Geisen et al. Transfusion. 2020 Oct.

Abstract

Background: The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S-303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment-emergent low titer non-hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re-formulated to decrease S-303 RBC adduct formation.

Study design and methods: A standard three-cell antibody screening panel was modified to include reagent red cells (RRC) with high (S-303H) or low (S-303L) S-303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion-dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay.

Results: Twelve (0.1%) of 10,721 general hospital and 5 (0.5%) of 998 repeatedly-transfused patients not previously exposed to amustaline/GSH RBCs expressed natural, low titer (2-32) IgM and/or IgG (non-IgG1 or IgG3 isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or non-acridine (n = 3) specificity. 11 of 17 sera reacted with S-303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatment-emergent S-303 antibodies were detected.

Conclusion: Standardized RRC screening panels are sensitive for the detection of natural and acquired S-303-specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naïve patients. The clinical relevance of these antibodies appears minimal but is under further investigation.

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References

REFERENCES:

    1. North A, Ciaravino V, Mufti N, et al. Preclinical pharmacokinetic and toxicology assessment of red blood cells prepared with S-303 pathogen inactivation treatment. Transfusion 2011;51:2208-18.
    1. Cancelas JA, Dumont LJ, Rugg N, et al. Stored red blood cell viability is maintained after treatment with a second-generation S-303 pathogen inactivation process. Transfusion 2011;51:2367-76.
    1. Henschler R, Seifried E, Mufti N. Development of the S-303 pathogen inactivation technology for red blood cell concentrates. Transfus Med Hemother 2011;38:33-42.
    1. Cancelas JA, Gottschall JL, Rugg N, et al. 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. Vox Sang 2017;112:210-8.
    1. Aydinok Y, Piga A, Origa R, et al. Amustaline-glutathione pathogen-reduced red blood cell concentrates for transfusion-dependent thalassaemia. Br J Haematol 2019;186:625-36.

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