Immunologic mechanisms of EPO-associated pure red cell aplasia

Pure red cell aplasia (PRCA) is a relatively rare condition defined as severe anemia secondary to the virtual absence of red cell precursors in the bone marrow. The incidence of PRCA was associated with subcutaneous administration of epoetin alfa (human recombinant erythropoietin [rHuEPO]). PRCA occurs from the generation of antibodies against rHuEPO, which neutralize not only the recombinant protein, but also native erythropoietin, resulting in the absence of red cell precursors in the bone marrow. Drug-induced PRCA has very similar characteristics to idiopathic PRCA, making the patients transfusion-dependent. Prior to 1998 only four cases had been associated with administration of rHuEPO; however, post-1998 a sharp increase in incidence was reported outside the United States. A change in formulation in 1998 was thought to be the reason for the induction of PRCA. A number of possible mechanisms have been proposed. The modification in the drug formulation probably played a major role. A sharp decrease of PRCA cases has been reported after 2002 related to the change in the mode of administration from subcutaneous to intravenous. In addition to the modification to the route of administration, revised storage and handling protocols have contributed to the reduced incidence of PRCA in the last 3 years. Nevertheless, the usefulness of this drug to the chronic renal patients who suffer from anemia far outweighs the disadvantages. Maintaining target hemoglobin levels, monitoring the response to erythropoietin, and adjuvant therapy to rHuEPO are all critical issues in the clinical management of renal and cancer patients with anemia.