therapy because of the limited information and high risk of infections. Rituximab Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody that targets the CD20 molecule present on mature B cells, which are the precursors of autoantibody- producing plasma cells. Rituximab can selectively deplete B-cells by mechanisms including antibody-dependent cell- mediated cytotoxicity, complement-mediated cytotoxicity and inhibition of cell proliferation with direct induction of B-cell apoptosis (Smith, 2003). Rituximab has been found to be useful in treating primary autoimmune hemolytic anaemia and thrombocytopenia (Quartier et al, 2001; Stasi et al, 2001) and several reports have shown that PRCA was successfully treated with rituximab in patients with B-cell lymphoproliferative disorders mainly consisting of CLL (Batlle et al, 2002; Ghazal, 2002; Gupta et al, 2002; Hegde et al, 2002; Ru & Liebman, 2003; Pantelidou et al, 2004; Narra et al, 2006). The maximum time for onset of response was 4 weeks. In two cases, where PRCA and the primary disorder were simultaneously diag- nosed, rituximab led to response in both PRCA and the primary disorder (Narra et al, 2006). One patient had a response to rituximab lasting only 4 weeks, but then responded to alemtuzumab (Ru & Liebman, 2003). No signiﬁcant side effects were reported in any of these patients treated with rituximab. Dungarwalla et al (2007) have shown that the results of rituximab therapy in patients with severe, resistant and life- threatening PRCA refractory to conventional immunosuppres- sion are disappointing. In their pilot study, all three of these patients with idiopathic PRCA did not respond to a conven- tional dose of rituximab (375 mg/m2) weekly for 4 weeks. Other therapeutic options Intravenous immunoglobulin In immunocompromised hosts, such as recipients of organ transplantation (Wong et al, 1999), patients infected with human immunodeﬁciency virus (HIV) (Frickhofen et al, 1990) or receiving chemotherapy (Song et al, 2002; Isobe et al, 2004), acute or chronic anaemia can develop following parvovirus B19 infection due to the lack of the production of speciﬁc antibodies. Chronic B19 infection-related PRCA is a treatable anaemia and demonstration of the virus DNA in blood by the polymerase chain reaction or dot-blot hybridization assays is essential. Intravenous immunoglobulin (IVIG) contains neu- tralizing antibody against parvovirus B19 and has been reported to be effective for chronic B19 infection-related anaemia in immunocompromised hosts. Recurrence of anae- mia is common in HIV-infected patients with low CD4+ T-cell counts (<0Æ08 0Æ1 · 109/l) and requires additional IVIG (Ramratnam et al, 1995). Anti-retroviral therapy may resolve chronic anaemia in HIV-infected patients (Mylonakis et al, Review 1999). IVIG may also be effective for PRCA due to parvovirus B19 in patients treated with rituximab (Sharma et al, 2000; Song et al, 2002). Alemtuzumab causes prolonged, severe CD4 and CD8 lymphopenia (Keating et al, 2002) and PRCA due to parvovirus B19 infection in a patient with cutaneous T-cell lymphoma treated with alemtuzumab has been reported (Herbert et al, 2003). Tacrolimus (FK506) is often associated with chronic B19 infection-associated anaemia in organ transplant recipients and cessation of tacrolimus or replace- ment with other immunosuppressants results in an improve- ment of anaemia (Wong et al, 1999). Thymectomy Surgical resection of thymomas has been recommended as the initial treatment of thymoma-associated PRCA, with an expected haematological response rate of 25–30% (Zeok et al, 1979). In recent reports, resection of the thymoma by itself was effective in remitting the anaemia in only a small percentage of patients (Mamiya et al, 1997; Thompson & Steensma, 2006) and a signiﬁcant fraction of patients developed PRCA after thymectomy (Suzuki et al, 2003; Thompson & Steensma, 2006; Hirokawa et al, 2008). Although the pathogenesis of thymo- ma-associated PRCA remains to be elucidated, there exist two potential mechanisms. Thymoma itself alters the subset and/or the repertoires of T lymphocytes, leading to the production of autoaggressive T-cell clones (Hoffacker et al, 2000). Another intriguing possibility is that thymectomy may represent a risk for the development of systemic autoimmune disorders over years (Gerli et al, 1999). Thompson and Steensma (2006) reported that surgical resection of thymoma was insufﬁcient for normalization of erythropoiesis in all 13 patients so treated, but immunosup- pressive therapy was effective as an adjuvant treatment. Immunosuppressive therapy including CS, CY and CsA has been reported to be useful in cases with thymoma-associated PRCA (Marmont et al, 1975; Garcia Vela et al, 1993; Charles et al, 1996; Thompson & Steensma, 2006), but optimal management of this disorder has remained unclear. Recently, it has been reported that thymoma-associated PRCA showed an excellent response to CsA and CsA-containing regiments were effective in preventing relapse (Hirokawa et al, 2008). Splenectomy, plasmapheresis, and bone marrow transplan- tation have been used on rare occasions and can be tried if all else fails. Peptide-based EPO receptor agonist Krantz and Kao (1967), for the ﬁrst time, reported that plasma from a patient with PRCA inhibited haem synthesis by the patient’s own bone marrow cells in vitro. The serum of patients with anti- EPO antibody-related PRCA also inhibited the growth of erythroid progenitor cells in vitro (Casadevall et al, 2002). PRCA due to autoantibodies against endogenous EPO occurs but is rare in patients who have never been treated with ª 2008 The Authors Journal Compilation ª 2008 Blackwell Publishing Ltd, British Journal of Haematology, 142, 505–514 509