Immune reconstitution following stem cell transplantation

Abstract

The period of immune deficiency following stem cell transplantation (SCT) results in significant morbidity and mortality. Whilst supportive therapies have partially improved the outcome of infective episodes, disease relapse remains a considerable obstacle to improvement in overall outcomes. An increased understanding of the importance of the immune system in preventing relapse has derived from studies in the allogeneic setting. Increasing awareness of autologous anti-tumor responses has also focused interest on enhancing such activity. Successful application of some of these newer therapies, such as tumor vaccination approaches, may depend critically on reconstitution of functional immune reactivity. Whilst early recovery of innate immunity (myeloid series and natural killer (NK) cells) results in reconstitution of protective immunity against many bacterial pathogens, both the absolute levels and function of T and B lymphocytes remain abnormal for many months or years. Incorporation of T-cell depletion, choice of graft type (both donor and source), development of graft-vs.-host disease and level of residual thymic activity can all influence aspects of the reconstitution process. Advances in immunological monitoring are providing new insights, particularly into the recovery of specific T-cell subsets. This review focuses mainly on recent advances in the understanding of immune reconstitution in the allogeneic setting.