Re-challenging patients who developed pure red cell aplasia with epoetin: can it be done?

Abstract

Most, if not all, nephrologists are aware of the explosion of epoetin-associated cases of pure red cell aplasia, particularly in Europe, from 1998 onwards [1–4]. The dramatic increase in reported cases was largely associated with a particular brand of epoetin alfa (Eprex; Erypo) [5], but a few cases have also been reported with epoetin beta [3]. Epoetin-associated pure red cell aplasia is characterized by a sudden loss of response to the drug, with the haemoglobin falling to 5 or 6 g/dl, and requiring regular blood transfusions to maintain a more respectable haemoglobin. The white cell and platelet counts are characteristically normal, but there is usually a profound decrease in circulating reticulocytes (to <10 10/l). Bone marrow examination usually shows a severe reduction in erythroblasts (to <5%) and/or evidence of red cell maturation arrest. Granulopoiesis and megakaryopoiesis is usually preserved. The condition is caused by the development of circulating anti-erythropoietin antibodies, which are usually initially detected by immunoassay, and subsequently confirmed to be neutralizing in a bioassay [1,6]. These antibodies crossreact with all commercially available erythropoietic products, as well as endogenous erythropoietin, and hence it is recommended that patients with this condition should not be switched to an alternative agent [3]. The condition is rare, and follow-up of most cases is too short to determine its natural course, but it is generally believed that immunosuppressive therapy may promote recovery [4]. We now report on three patients who developed epoetin-associated pure red cell aplasia, who were treated with immunosuppressive therapy, and who have now been re-challenged with another epoetin.