CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation

Objective Acute graft-vs-host disease (aGVHD) remains an important cause of morbidity after reduced-intensity conditioning (RIC) allogeneic transplantation (allo-SCT). It has been shown that antithymocyte globulin (ATG) dose infused during RIC is a major determinant for the likelihood of developing aGVHD. The ATG modulation on aGVHD is likely related to in vivo T-cell depletion. Patients and methods We therefore investigated the relationship between the cellular composition of the allograft and clinical outcome in 57 patients who received allogeneic peripheral blood stem cells from HLA-identical siblings following an ATG-based RIC. Results In a multivariate analysis, the CD8+ T cell dose infused was the only parameter associated with the risk of aGVHD (p = 0.031; RR = 1.96; 95% CI, 1.1–3.6). When looking at the extremes, patients experiencing grade III–IV aGVHD received a median of 143 × 106/kg CD8+ T cells, while patients without aGVHD received a median of 96 × 106/kg CD8+ T cells (p = 0.021). None of the different cell subtypes contained in the allograft was associated with a significant probability of developing chronic GVHD. Patients with grade II aGVHD who received an intermediate dose of CD8+ T cells (median, 111 × 106/kg) had a significantly better overall survival in comparison to patients with grade 0–I or grade III–IV aGVHD (p = 0.009). Conclusion In comparison to myeloablative allo-SCT, these results demonstrate that a cautious monitoring of the number of cells infused, at least in the context of ATG-based RIC, may represent an important predictive indicator of early transplant-related events and outcome after RIC allo-SCT.