OA1-AM24-MN-23 - HLA Alloimmunization in ReCePI, a Phase III Study of Amustaline/Glutathione Pathogen Reduced RBCs

Alloimmunization to human leukocyte antigens (HLA) is a known side-effect of transfusion, which can complicate subsequent platelet transfusion or organ transplantation. The risk in recipients of amustaline/glutathione(GSH) PR red blood cells (RBCs) has not been reported.

Study

Design/Methods:

In the ReCePI Phase III clinical study (funded by the Biomedical Advanced Research Development Authority, DHHS; ClinicalTrials.gov, NCT03459287), complex cardiac or thoracic aorta surgery patients were transfused with PR vs. control, leukoreduced RBCs during and for 7 days post-surgery. Samples were collected pre-transfusion and on day 28 and tested for HLA antibodies using a fluorescent bead-based screening assay.  Antibody levels were examined at low, medium, and high cutoff values, using 3 SD and 5 SD above the mean values previously reported in non-transfused males.

Results/Findings:

The study included 114 participants (51% female) in the PR and 113 (53% female) in the control arms who had pre- and post- study transfusion samples available, a subset of the 321 ReCePI evaluable subjects.  In the PR arm 80 participants received exclusively PR RBC units, and 34 also received non-study RBC units.  In a modified intention to treat analysis, there was no signal that PR RBCs affected the rate of HLA Class I or II antibody formation (Table 1).  Similar results were seen in a study RBC only analysis, with OR 1.4 (95% CI 0.59 – 3.2) for new HLA Class I and OR 0.88 (95% CI 0.31 – 3.0) for new HLA Class II antibodies at the high cutoff.  Female transfusion recipients had higher risk of developing new high-level HLA Class I antibodies, OR 9.0 (95% CI 2.8 – 29), and HLA Class II antibodies, OR 5.0 (95% CI 1.4 – 17).  The mean number of RBC transfusions (5.5 vs. 3.6 units, p=0.016) and concurrent platelet transfusions (1.8 vs. 1.1 units, p=0.037) was higher in those who developed new high-level HLA Class II antibodies. Intensity of transfusion did not correlate with risk of HLA Class I alloimmunization, and plasma transfusion exposure intensity did not affect HLA Class I or II alloimmunization risk.

Conclusions:

Receipt of amustaline/GSH PR RBC units did not affect HLA alloimmunization risk.  Female sex was a risk factor for development of new high-level HLA Class I and II antibodies.  Risk of new high-level HLA Class II antibodies correlated with the number of platelet and RBC but not plasma transfusions, potentially due to higher levels of passenger WBCs in the two cellular products, despite leukoreduction.