Impact of very early CD4(+) /CD8(+) T cell counts on the occurrence of acute graft-versus-host disease and NK cell counts on outcome after pediatric allogeneic hematopoietic stem cell transplantation

Abstract

Background: Increasing evidence suggests that early and rapid lymphocyte recovery following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with better survival.

Procedure: We retrospectively analyzed very early lymphocyte subset counts following transplantation from our 5-year pediatric allogeneic HSCT material to find clinically relevant associations with post transplant outcome, and the major complication of HSCT, acute graft-versus-host disease (aGVHD). We analyzed HSCTs performed due to acute leukemias and lymphomas from matched unrelated donors (MUD, n = 33), unrelated cord blood (UCB, n = 9) and matched sibling donors (MSD, n = 17).

Results: Patients with grafts from MUDs and grade II-IV aGVHD) had higher (median 2.1 compared to 0.3, P<0.0001) and earlier (at day +18 post transplant vs. day +25, P = 0.004) first measurable CD4(+) /CD8(+) T cell ratio, compared to patients with no or grade I aGVHD, respectively. At day +32 after HSCT patients with MUDs and significant aGVHD had higher levels of both CD4(+) and CD8(+) T cell subsets. Low (below median 120/µL) versus high natural killer (NK) cell counts at day +32 were associated with 3-year event-free survival of 27.4 +/- 9.0% versus 82.4 +/- 6.4% (P < 0.0001), cumulative transplant-related mortality of 44.7 +/- 12.2% versus 3.0 +/- 3.0% (P < 0.001) and cumulative relapse incidence of 50.4 +/- 12.2% versus 15.0 +/- 6.2% (P = 0.019), respectively.

Conclusions: We conclude that early lymphocyte subset counts following allogeneic HSCT have an association with aGVHD and post transplant outcome.

Keywords: allogeneic stem cell transplantation; graft-versus-host disease; lymphocyte reconstitution; lymphocyte subsets.