Autoimmunity and Its Treatment in Aplastic Anemia

A century ago, long before much was understood about blood cell production, astute clinicians inferred from the fatty bone marrow of their patients who had died of aplastic anemia a fundamental failure of hematopoiesis [1]. This conclusion has been fully confirmed by modern laboratory testing, including flow cytometric measurements of primitive blood cells that bear the CD34 antigen and tissue culture assays for progenitor and stem cells [2]. Severe aplastic anemia, which is characterized by profound depression of neutrophil, platelet, and erythrocyte counts, could not be effectively treated until bone marrow transplantation was developed in the 1970s. An adequate inoculum of bone marrow cells from an immunologically well-matched sibling donor was shown to correct the suspected simple deficiency of stem cells. The reason why the blood-forming bone marrow cells disappeared in the first place was unknown, but direct toxicity was suggested by two models: 1) the transient aplasia that regularly occurs with large doses of radiation or cytotoxic drugs used to treat cancer and 2) the relation between aplastic anemia and exposure to certain chemicals and drugs (most notoriously benzene and chloramphenicol), established from case histories and epidemiologic studies.