Blood stem cell transplantation: Factors influencing cellular immunological reconstitution

Recovery of immune function following stem cell transplantation is necessary for a good outcome. Immune recovery is facilitated by transplanting higher numbers of cells than neutrophil or platelet reconstitution requires. Estimates from studies in the allogeneic setting suggest the minimum stem cell dose to achieve optimal lymphocyte recovery is about 10⁷ CD34⁺ cells/kg. Increasing the number of autologous stem cells infused potentially increases the risk of reinfusing tumor cells. Transplanted mature immune cells apparently have very limited early contribution to cellular immune recovery. Mobilizing cytokines permit collection of greater numbers of stem cells, but they also can polarize T cells with potentially significant consequences, for example, granulocyte colony-stimulating factor (G-CSF) decreases the antitumor cytotoxic effector functions of cells. Although this could be a disadvantage in the autologous setting, it might decrease graft versus host disease in the allogeneic setting. Thus, identification of cytokines, which alone or in combination provide the most potent mobilizing effect to permit the collection of the highest number of stem cells without inadvertent detrimental polarization of the responses of immune cells, and employment of cytokines post-transplantation, which direct differentiation of the stem cells along the most desirable pathways, for example, to generate antitumor immune responses, might improve immunological outcome. A future emphasis should be to better define the cytokines and target cell populations that provide optimal immune reconstitution rather than focusing solely on rapid hematological recovery. More complete immunological reconstitution in a greater proportion of patients should be accompanied by improvements in outcomes of blood stem cell transplantation.