Bone marrow and blood demonstrate distinct immune reconstitution patterns and correlations with relapse post-transplant Open Access

• Marrow and blood showed distinct patterns of immune reconstitution post-transplant with differences in lymphocyte subsets and phenotypes.

• Innate lymphocytes were relatively more frequent in the marrow; T cell PD1 expression correlated with leukemia relapse.

The bone marrow represents the tumor microenvironment for many hematologic malignancies and a potentially critical site for alloimmunity following hematopoietic transplantation. Despite the importance of immune reconstitution (IR) post-transplant, marrow IR data are limited, and insights are largely derived from studies of peripheral blood (PB). We investigated lymphocyte IR longitudinally in marrow (n=110) and PB (n=115) samples from adults undergoing allogeneic transplantation for hematologic malignancies (n=33). This transplant cohort included a diverse representation of graft sources (mobilized peripheral blood, CD34-selected grafts, and umbilical cord blood) and degrees of HLA mismatch. Natural killer (NK) cells quickly expanded within the first 30 days post-transplant in both marrow and PB, but were then outnumbered by T cells in PB after day 100. In contrast, NK cells remained dominant in the marrow at day 100 (p<0.01, paired Wilcoxon signed-rank test), and thereafter marrow T and NK cell frequencies were similar throughout year-one. Tissue-specific features post-transplant included fewer regulatory T cells, more innate lymphoid cells, and increased CD69 expression on lymphocytes in marrow compared to PB. Furthermore, day 100 PD1 expression on marrow T cells was greater in non-relapsing patients than those who subsequently relapsed. These findings reveal persistent NK dominance of the marrow early post-transplant and suggest correlations between marrow immunity and clinical transplant outcomes.