Collection and processing of hematopoietic progenitor cell products at risk of presenting with cold agglutination

Background aims: Cold agglutinins are commonly identified in transfusion laboratories and are defined by their ability to agglutinate erythrocytes at 3-4 & DEG;C, with most demonstrating a titer >64. Similarly, cryoglobu-lins can precipitate from plasma when temperatures drop below central body temperature, resulting in erythrocyte agglutination. Thankfully, disease associated from these autoantibodies is rare, but unfortu-nately, such temperature ranges are routinely encountered outside of the body's circulation, as in an extra-corporeal circuit during hematopoietic progenitor cell (HPC) collection or human cell therapy laboratory processing. When agglutination occurs ex vivo, complications with the collection and product may be encountered, resulting in adverse events or product loss. Here, we endeavor to share our experience in pre-venting and responding to known cases at risk of or spontaneous HPC agglutination in our human cell ther-apy laboratory.Case reports: Four cases of HPC products at risk for, or spontaneously, agglutinating were seen at our institu-tion from 2018 to 2020. Planned modifications occurred, including ambient room temperature increases, tan-dem draw and return blood warmers, warm product transport and extended post-thaw warming occurred. In addition, unplanned modifications were undertaken, including warm HPC product processing and plasma replacement of the product when spontaneous agglutination of the product was identified. All recipients suc-cessfully engrafted after infusion. Conclusions: While uncommon, cold agglutination of HPC products can disrupt standard processes of collec-tion and processing. Protocol modifications can circumvent adverse events for the donor and minimize prod-uct loss. Such process modifications should be considered in individuals with known risks for agglutination going to HPC donation/collection.& COPY; 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.