Host T Cells Affect Donor T Cell Engraftment and Graft-versus-Host Disease after Reduced-Intensity Hematopoietic Stem Cell Transplantation

The magnitude and duration of mixed chimerism in the T cell compartment is variable after TID-RIST with TCD. A, Peripheral blood T cell donor chimerism after TCD (top) and TCR (bottom) RIST. B, Two patterns of donor T cell engraftment are seen after TCD-RIST. (Top) Rapid engraftment was characterized by stable complete donor T cell chimerism by day +42, prior to DLI. (Bottom) MC_T was characterized by variable donor cbimerism in the T cell compartment, and FDC_T established after administration of DLI. Black bars: median values; shaded bars: first and third quartiles; lines: ranges.

Progression toward FDC_T is uneven after TCD RIST. Lines connect T cell chimerism data points for individual subjects with MC_T; shaded area: donor chimerism 90%; solid lines: patients with less than grade II aGVHD; dotted lines: patients who developed grades II-IV acute GVHD; open triangle: cyclosporine taper; arrows: scheduled DLI.

aGVHD was observed at or after establishment of FDC_T regardless of DLI administration. A, All 7 of the patients in the rapid engraftment subgroup developed aGVHD, including 3 prior to receiving any scheduled DLI. aGVHD occurred in 4 of 10 patients with MC_T. The shaded triangle, below the line connecting symmetrical time points, represents the theoretical area in which values would fall if subjects developed aGVHD at or before the establishment of FDC_T. Arrows: scheduled DLI. B, Incidence and onset of aGVHD after TCD according to number of scheduled DLI received.

Although host CD8⁺ T cell counts were associated with MC_T there was no direct association with aGVHD. Postinduction circulating CD8⁺ T cell counts in TCD recipients with MC_T and rapid FDC_T (left panel) and grade 0-I versus II-IV aGVHD (right panel). Bars: median values.

Patterns of T cell recovery after TCD. A, Recovery of circulating T cells in TCD recipients with MC_T and rapid FDC_T shows host but not donor T cell counts are affected by engraftment kinetics. B, Host versus donor T cell recovery in those with grade 0-I versus II-IV aGVHD suggest greater donor T cell expansion in those who develop aGVHD. Black bars: median values; shaded bars: first and third quartiles, and lines: range.