CD34 cell dose and chronic graft-versus-host disease after human leukocyte antigen-matched sibling hematopoietic stem cell transplantation

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent reports suggest that chronic GVHD is more frequent after G-CSF - mobilized peripheral blood mononuclear cell (G-PBMC) transplantation compared to marrow transplantation from human leukocyte antigen (HLA)-matched siblings. Furthermore, higher numbers of CD34 positive cells in G-PBMC grafts were associated with an increased risk of chronic GVHD, whereas a correlation between CD34 cell numbers and chronic GVHD has not been reported after bone marrow transplantation. Potential mechanisms that might explain the association between G-PBMC CD34 numbers and chronic GVHD include enhanced antigen presentation to donor T cells by large numbers of transplanted CD34 cells or their dendritic cell progeny, which may enhance GVHD induction. However, these mechanisms remain highly speculative and are not supported by experimental data. This review discusses implications of CD34 cell dose adjustments in HLA-identical sibling G-PBMC transplantation and weighs the benefits and risks with respect to chronic GVHD, hematopoietic recovery, immune reconstitution and relapse.