Summary and Conclusions

Abstract

The management of aplastic anemia continues to challenge clinical investigators because the pathophysiology of the aplastic and hypoplastic syndromes is heterogeneous and poorly understood. The field can be further confused by investigators who assign pathophysiologic mechanisms as a result of therapeutic experiences. For example, the response of aplastic anemia to androgen therapy implies to some that the disease might be due to a deficiency of one or more growth factors or to a defect in the response of progenitor cells to normal or even elevated levels of growth factors. On the other hand, the response of aplastic anemia to bone marrow transplantation suggests that the disease could be due to destruction or dysfunction of stem cells or progenitor cells, while the response to prednisone of a single cell deficiency such as Diamond — Blackfan anemia suggests that the disorder may be due to failure of committed progenitor differentiation due perhaps to reduction of steroid-sensitive expression of a specific growth factor receptor gene. Finally, the response of aplastic anemia to antithymocyte globulin or cyclosporine or sometimes prednisone creates the impression that aplastic anemia is frequently an autoimmune disorder involving suppressor T cells. Indeed some cases of aplasia, particularly the single cell deficiencies, have been clearly associated with suppressing lymphocytes exhibiting a unique phenotype.¹ Rarely serum antibodies reactive with committed progenitor cells have been detected.² Therefore, there is little question that some cases of aplastic anemia are associated with dysregulation of the immune response, but whether the instigating agent is an autoantigen or, as seems more likely, a poorly regulated response to viral invasion of stem and/or progenitor cells is yet to be determined.