Rechallenge with rhEPO preparations may cause an anamnes- tic antibody response, making it less possible for the antibody to either spontaneously disappear or return to clinically unimportant levels, and may induce the formation of allergic skin and systemic reactions (Weber et al, 2002). Recently, a novel peptide-based EPO receptor agonist called Hematide, which does not cross-react with anti-EPO antibod- ies, has been developed (Stead et al, 2006). Hematide is a synthetic, dimeric peptidic erythropoiesis-stimulating agent covalently linked to polyethylene glycol and is being developed for the treatment of anaemia associated with chronic renal failure and cancer. Because its primary amino acid sequence is unrelated to that of rhEPO, Hematide is unlikely to induce a cross-reactive immune response against endogenous EPO and is reported to correct anaemia induced by anti-rhEPO antibodies in a rat PRCA model (Woodburn et al, 2007). Feasibility of long-term maintenance§ Unacceptable for the dose to maintain remission May be durable but needs careful monitoring Mean time to response 2Æ5 weeks 9 weeks in patients with primary idiopathic PRCA (33% of patients achieved remission within 2 weeks) 12 weeks in patients with primary idiopathic PRCA (65% of responders achieved remission within 2 weeks) Need for maintenance therapy Required (Most patients relapsed during the taper of CS) Required in patients with primary idiopathic PRCA Required in patients with primary idiopathic PRCA (86% relapsed after discontinuation of CsA while 11% relapsed during the maintenance of CsA) Unknown: required in some patients Review recombinant human EPO (rhEPO). rhEPO-related PRCA reached a peak incidence mainly in Europe in 2001 to 2002, largely related to a change of formulation, and of uncoated rubber stoppers (leachates present), in a particular rhEPO product, Eprex, and subcutaneous administration (Casadevall et al, 2002; Rossert et al, 2004). The two most important initial steps in the management of anti-EPO antibody-mediated PRCA are transfusions for symptomatic anaemia and stopping the administration of rhEPO (Rossert et al, 2004). Since PRCA in this setting is immune-mediated, and since spontaneous remissions after cessation of rhEPO therapy are rare, immunosuppressive therapy should be provided in most cases (Verhelst et al, 2004; Rossert et al, 2005). Anti-rhEPO antibodies cross-react not only with the endogenous hormone, but also with all rhEPO molecules, including darbepoetin alfa (Casadevall et al, 2002). Table I. Treatment of pure red cell aplasia (PRCA). Agent Corticosteroids; CS (methyl-prednisolone/ prednisone/prednisolone) Response rate (CR + PR)* 30–62% Cyclosporine A; CsA 65–87% Cyclophosphamide; CY (CY + CS) Agent Corticosteroids; CS (methyl-prednisolone/ prednisone/prednisolone) Cyclosporine A; CsA Cyclophosphamide; CY (CY + CS) 7–20% (40–60%) 11 weeks Unacceptable Relapse free survival (RFS) Median overall survival (OS) 80% of patients relapse within 24 months after remission during dose-reduction Median RFS: 33 months in patients with primary idiopathic PRCA (88% of patients relapsed during CS maintenance) Median RFS: 103 months in patients with primary idiopathic PRCA (Including patients who relapsed after the discontinuation of CsA) Unknown: the duration of remission induced by CY seems to be prolonged as compared to patients induced by CS* 14-year OS in patients with primary idiopathic PRCA treated with CS or with various combinations except for CsA 12-year OS in patients with primary idiopathic PRCA responding to remission induction therapy with CsA 10-year OS was 95% and the median OS has not yet been reached in all patients Unknown Patients with primary acquired and secondary PRCA are included if not otherwise indicated. *References are indicated in the text. Referenced by Clark et al (1984). Referenced by Sawada et al (2007). §Referenced by Clark et al (1984), Sawada et al (2007), Radis et al (1995) and Reinhold-Keller et al (2000). 510 ª 2008 The Authors Journal Compilation ª 2008 Blackwell Publishing Ltd, British Journal of Haematology, 142, 505–514