Differential Distribution of Activated Innate and Adaptive Immune Subsets in G-CSF Mobilized Hematopoietic Stem Cell Allografts May Influence Incidence of Acute (aGVHD) and Chronic Graft-Versus-Host Disease (cGVHD)

Median numbers of activated NK cells (CD3⁻CD56⁺CD16⁺CD69⁺) cells were significantly higher in pts with vs. without aGVHD (586.4/μL vs. 270.5/μl, p=0.003). Higher median numbers of resting NK cells (CD3⁻CD56⁺CD16⁺) and activated B cells (CD19⁺CD80⁺) were associated with cGVHD but not aGVHD. Non-zero levels of CD4⁺ T cells expressing prostaglandin D2 (PGD2) receptor (CD4⁺CD294⁺), chemokine receptor CCR3 (CD4⁺CD193⁺), chemokine receptor 4 CCR4 (CD4⁺CD194⁺) and CXCR3 (CD4⁺CD183⁺) in the allograft were associated with lower incidence of cGVHD. Also CD4⁺ T cells expressing both CCR4 and PGD2 receptors were associated with lower incidence of cGVHD. Significant differences were seen in median numbers (Table 1) and % of non-zero values (Table 2) of NK cells, B cells, and activated CD4⁺ T cells between those who did vs. did not develop cGVHD. Immunophenotypic analyses of pts receiving these allografts at days 30 and 100 post transplant were also performed. Updated results about correlation of these subsets between allografts and post-transplant patient samples will be presented. Multivariate analyses of these subsets in conjunction with clinical factors are being performed. In conclusion, activated B cells in the allograft may influence the incidence of cGVHD; in particular B cells expressing CD80, a co-stimulatory molecule for T cells and their association with cGVHD confirms results from murine models. Interestingly, CD4⁺ T cells associated with lower incidence of cGVHD expressed receptors for chemokines, CXCR3 and prostaglandin D2. These homing receptors are up regulated selectively in CD4⁺ T cells in the absence of chronic GVHD, suggesting a protective role for these receptors in the pathogenesis of cGVHD. Activated and resting NK cells were also associated with acute and chronic GVHD respectively. These results showing an association of specific immune subsets in the allograft and GVHD may provide opportunities for therapeutic interventions for graft engineering.

Off Label Use: Lenalidomide in AML. Jaglowski:Pharmacyclics: Research Funding. Benson:Innate Pharma: Research Funding. Devine:Sanofi: Honoraria, Research Funding.