Analysis of Cell Subsets in Donor Lymphocyte Infusions from HLA Identical Sibling Donors after Allogeneic Hematopoietic Cell Transplant

Donor lymphocytes infusions (DLIs) are a major therapeutic approach to treat relapse and mixed chimerism after allogeneic hematopoietic cell transplant (alloHCT). The impact of the composition regarding different cell subsets in the development of graft-versus-host disease (GVHD) is not fully understood. We performed a cell subsets analysis of 56 DLIs from fully HLA-compatible identical matched sibling donors (MSDs) in 36 alloHCT patients and studied its association with GVHD. A median of one DLI was infused per patient. Fourteen patients (38%) developed GVHD. The cell composition analysis of the first DLI (DLI1) showed that a high dose of B cells (P = .03) and CD27⁺ B cells (P < .01) was associated with GVHD. We identified DLI dose cutoff points for several cell populations above which GVHD was more frequent (CD8⁺ T_N >3 × 10⁶ cells/kg, CD27⁺ B cells >2.6 × 10⁶/kg, CD27⁺ NK >0.35 × 10⁶ cells/kg, and mononuclear cells >0.83 × 10⁸/kg). Noteworthy, the proportion of CD4⁺ naive T cells (T_N) or unselected T_N was not linked with GVHD and a DLI1 containing a higher dose of regulatory T cells was not protective for GVHD. We studied several transplant clinical variables and did not find any association with GVHD. Altogether, this study provides a comprehensive analysis of the cell populations in a DLI from MSDs and identifies potential key cell subsets, which provides insight for the understanding of GVHD after DLI.