Chatacterizing NK cell recovery following haploidenitical hematopoietic stem cell transplantation and post-transplant cyclophosphamide via high dimensional flow cytometry 4068

Description Natural killer (NK) cells are among the first immune cells to recover after allogeneic hematopoietic cell transplantation (HCT). Haploidentical HCT (haplo-HCT), while potentially curative, is associated with increased risk of graft-versus-host disease (GvHD) and opportunistic infections such as cytomegalovirus (CMV). Recently, post-transplant cyclophosphamide (PTCy) has significantly reduced GvHD and other complications associated with haplo-HCT. In this study, we investigated markers of NK cell development, activation, tissue homing, memory, regulatory pathways, and lineage in haplo-HCT, and their relationship to post-HCT outcomes including GvHD and CMV reactivation. Using a 36-color high-dimensional antibody panel and spectral flow cytometry, we analyzed 18 patients undergoing haplo-HCT/PTCy at various time points and compared them to pre-HCT donor samples. Preliminary results from day 21 post-transplant show distinct NK cell clusters between patient and donor samples, as observed in UMAP and t-SNE plots. The differences indicate a highly proliferative NK cell population (Ki67+) with reduced expression of CD16 and CD57, suggesting a less mature, less cytotoxic phenotype. However, CCR5 expression was significantly higher in patient samples, suggestive of higher tissue infiltration which may aid in CMV control. We are further analyzing samples from 30–180 days post-transplant to better understand NK cell reconstitution and its role in post-transplant outcomes. Funding Sources NIH Topic Categories Transplantation Immunology (TRAN)