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

Abstract 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.