Human leukocyte antigen alloimmunization in a randomized trial of amustaline/glutathione pathogen‐reduced red cells in complex cardiac surgery patients

• Published in: Transfusion (Philadelphia, Pa.) Vol. 65; no. 3; pp. 459 - 465
• Main Authors: Norris, Philip J., Stone, Mars, Di Germanio, Clara, Balasko, Brendan, Kaidarova, Zhanna, Friend, Henry, Varrone, Jeanne, Corash, Laurence, Mufti, Nina, Benjamin, Richard J.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2025; Wiley Subscription Services, Inc
• Subjects: Acridines; Aged; Antibodies; Antigens; Aorta; blood component preparations; Blood transfusions; Cardiac Surgical Procedures; Erythrocyte Transfusion - adverse effects; Erythrocyte Transfusion - methods; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - immunology; Erythrocytes - microbiology; Female; Females; Glutathione; Glutathione - administration & dosage; Heart; Histocompatibility antigen HLA; HLA Antigens - immunology; Humans; immunology (other than RBC serology); Isoantibodies - blood; Isoantibodies - immunology; Isoimmunization; Leukocytes; Male; Middle Aged; Nitrogen Mustard Compounds; Pathogens; Platelets; RBC transfusion; Risk factors; Surgery; Thorax; Transfusion; RBC transfusion; immunology (other than RBC serology); blood component preparations
• ISSN: 0041-1132; 1537-2995; 1537-2995
• DOI: 10.1111/trf.18131

Background Although alloimmunization risk of pathogen‐reduced (PR) platelets has been studied, the risk has not been reported with PR red blood cells (RBCs). Study Design and Methods In a Phase III, randomized, controlled trial (Red Cell Pathogen Inactivation), cardiac or thoracic‐aorta surgery patients were randomized to transfusion with amustaline/glutathione PR versus conventional RBCs. Pre‐transfusion and Day 28 samples were evaluated for Human leukocyte antigen (HLA) Class I and Class II antibodies at low, medium, and high cutoff values. Results The HLA alloimmunization analysis included 114 participants (53% female) in the PR and 113 (51% female) in the conventional RBC arms. In a modified intention‐to‐treat analysis, 13.7% (N = 29) and 7.2% (N = 15) developed new high‐level HLA Class I or Class II antibodies, respectively; however, there was no signal that PR‐RBCs affected the rate of HLA Class I (odds ratio (OR) 1.3 [95% confidence interval (CI) 0.62–2.9]) or Class II antibody formation (OR 0.99 [95% CI 0.35–2.8]). Female transfusion recipients had higher risk of developing new high‐level HLA Class I antibodies (OR 12.0 [95% CI 3.5–40.9]) and Class II antibodies (OR 5.0 [95% CI 1.4–17]). The mean number of RBC (5.5 vs. 3.6 units, p = 0.018) and platelet (1.8 vs. 1.1 units, p = 0.043) transfusions was higher in subjects with new high‐level HLA Class II antibodies. Discussion Receipt of amustaline/glutathione PR‐RBC units did not affect HLA alloimmunization risk. Female sex and number of RBC and platelet transfusions were risk factors for the development of new high‐level HLA Class I and Class II antibodies.