Th234 - The Blood and Bone Marrow Have Distinct Patterns of Innate and Adaptive Lymphoid Immune Reconstitution in Humans Following Allogeneic Hematopoietic Cell Transplantation

Jason Kuttiyara – Memorial Sloan Kettering Cancer Center; Paola Vinci – Memorial Sloan Kettering Cancer Center; John Slingerland – Memorial Sloan Kettering Cancer Center; Zoe Katsamakis – Memorial Sloan Kettering Cancer Center; LeeAnn Marcello – Memorial Sloan Kettering Cancer Center; Paul Giardina – Memorial Sloan Kettering Cancer Center; William Donohoe – Memorial Sloan Kettering Cancer Center; Richard Lin – Memorial Sloan Kettering Cancer Center; Esperanza Papadopoulo – Memorial Sloan Kettering Cancer Center; Boglarka Gyurkocza – Memorial Sloan Kettering Cancer Center; Brian Shaffer – Memorial Sloan Kettering Cancer Center; Martin Tallman – Memorial Sloan Kettering Cancer Center; Ioannis Politikos – Memorial Sloan Kettering Cancer Center; Sergio Giralt – Memorial Sloan Kettering Cancer Center; Juliet Barker – Memorial Sloan Kettering Cancer Center; Miguel-Angel Perales – Memorial Sloan Kettering Cancer Center; Roni Tamari – Memorial Sloan Kettering Cancer Center; Christina Cho – Memorial Sloan Kettering Cancer Center; Marcel van den Brink – Memorial Sloan Kettering Cancer Center; Hanash Alan – Memorial Sloan Kettering Cancer Center

Abstract Text: In myeloid hematologic malignancies, the bone marrow (BM) represents the tumor microenvironment, a potentially key site of anti-leukemic immunity following allogeneic hematopoietic cell transplantation (allo-HCT). Despite the importance of immune reconstitution (IR) after allo-HCT, IR data in BM are limited and much of our understanding arises from peripheral blood (PB) studies. We hypothesized that lymphocyte reconstitution in BM may be distinct from that of PB, and that characterization of BM IR may elucidate populations associated with outcomes. To test this, we prospectively compared IR via multicolor flow cytometry on fresh serial BM and PB samples (n=110 BM, n=115 PB) from pre-transplant (recipient) to one-year post-transplant in 33 adults with hematologic malignancies undergoing allo-HCT at our institution. We found that NK cells were the first lymphocytes to emerge in BM and PB, but NK cells continued to outnumber T cells in BM after their frequencies became similar in PB by day 100. Additionally, while T cells outnumbered NK cells as a percentage of lymphocytes in PB thereafter, NK and T cell frequencies in BM were similar for the duration of year-one. Furthermore, CD69 expression was significantly greater in BM compared to PB for T and NK cells by day 100, suggesting potential acquisition of a tissue-resident profile. Though rare, ILC1/2/3s had distinct distributions and phenotypes (increased CD69 in BM, increased CD25 in PB) in blood and marrow. Our work reveals tissue-specific features of lymphocytes in BM following allo-HCT, underscoring the importance of tissue-level studies of clinically relevant immune subsets in humans.