Variable impact of graft CD3 cell content on graft versus host disease in hematopoietic stem cell transplant recipients: Is the role of donor CD3 cells overestimated?

Graft cellular composition is considered as a significant determinant of transplant outcome. Donor CD3 cells were shown to have a significant association with the development of graft vs host disease (GvHD). The aim of this study was to investigate the impact of graft CD3 cell content on transplant outcome, particularly in terms of GvHD and relapse. We retrospectively analysed the records of 515 allo-HCT recipients [median age: 37(15-71) years; male/female: 323/192]. The optimal threshold of infused CD3 cell count for acute GvHD development was estimated to be 197.5 × 10/kg (AUC: 0.572; 95 % CI: 0.513-0.631; p = 0.018) and 198.5 × 10/kg (AUC: 0.6; 95 % CI: 0.520-0.679; p = 0.019) for the general population and reduced-intensity conditioning (RIC) subgroup, respectively. Acute GvHD was more frequent in low-CD3 group in the whole study population, particularly in RIC transplants. The incidence of cytomegalovirus reactivation was higher in low-CD3 group and neutrophil engraftment occured earlier in the same group of patients. Overall survival and non-relapse mortality were comparable between high and low-CD3 groups. Age, ECOG performance status, hypogammaglobulinemia, chronic GvHD and post-transplant relapse were found to predict prognosis in multivariate analysis. By focusing mainly on donor T cells, the potential role of host immune cells in the early post-transplant milieu may have been underestimated. Drawing a more detailed profile of graft and host immune cells in the joint microenvironment may elucidate our way to a better understanding of GvHD pathogenesis. By this way a comprehensive pre-transplant risk assessment could be improved to generate more personalized approaches.