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

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.