Blood stem cell transplantation: Factors influencing cellular immunological reconstitution

Recovery of immune function following stem cell transplantation is necessar y for a good outcome. Immune recovery is facilitated by transplanting highe r numbers of cells than neutrophil or platelet reconstitution requires. Est imates from studies in the allogeneic setting suggest the minimum stem cell dose to achieve optimal lymphocyte recovery Is about 10(7) CD34(+) cells/k g. Increasing the number of autologous stem cells infused potentially incre ases the risk of reinfusing tumor cells. Transplanted mature immune cells a pparently have very limited early contribution to cellular immune recovery. Mobilizing cytokines permit collection of greater numbers of stem cells, b ut 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 d isadvantage 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 permi t the collection of the highest number of stem cells without inadvertent de trimental polarization of the responses of immune cells, and employment of cytokines posttransplantation, which direct differentiation of the stem cel ls along the most desirable pathways, for example, to generate antitumor im mune responses, might improve immunological outcome. A future emphasis shou ld be to better define the cytokines and target cell populations that provi de optimal immune reconstitution rather than focusing solely on rapid hemat ological recovery. More complete immunological reconstitution in a greater proportion of patients should be accompanied by improvements in outcomes of blood stem cell transplantation.