Bone marrow and blood demonstrate distinct immune reconstitution patterns and correlations with relapse posttransplant

The bone marrow represents the tumor microenvironment for many hematologic malignancies and a potentially critical site for alloimmunity after hematopoietic transplantation. Despite the importance of immune reconstitution (IR) after 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 samples (n = 115) from adults undergoing allogeneic transplantation for hematologic malignancies (n = 33). This transplant cohort included a diverse representation of graft sources (mobilized PB, CD34-selected grafts, and umbilical cord blood) and degrees of HLA mismatch. Natural killer (NK) cells quickly expanded within the first 30 days after transplant in both the 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 < .01, paired Wilcoxon signed-rank test), and thereafter marrow T and NK cell frequencies were similar throughout year 1. Tissue-specific features after transplant included fewer regulatory T cells, more innate lymphoid cells, and increased CD69 expression on lymphocytes in the marrow compared with PB. Furthermore, day 100 PD1 (programmed cell death protein 1) expression on marrow T cells was greater in nonrelapsing patients than those who subsequently relapsed. These findings reveal persistent NK dominance of the marrow early after transplant and suggest correlations between marrow immunity and clinical transplant outcomes.