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 × 106/kg (AUC: 0.572; 95 % CI: 0.513-0.631; p = 0.018) and 198.5 × 106/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.