review Acquired pure red cell aplasia: updated review of treatment Kenichi Sawada,1 Naohito Fujishima1 and Makoto Hirokawa1,2 1Department of Internal Medicine III, Division of Haematology, Akita University Graduate School of Medicine, and 2Oncology Centre, Akita University Graduate School of Hospital, Akita, Japan OnlineOpen: This article is available free online at www.blackwell-synergy.com Summary Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immuno- logically-mediated disease. Although vigorous immunosup- pressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of ﬁrst choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs. Keywords: pure red cell aplasia, corticosteroids, cyclospor- ine A, cyclophosphamide, alemtuzumab, rituximab. Pure red cell aplasia (PRCA), a disorder ﬁrst characterized in 1922 (Kaznelson, 1922), is a syndrome characterized by severe normochromic, normocytic anaemia associated with reticulo- cytopenia and absence of erythroblasts from an otherwise normal bone marrow. PRCA may appear as a congenital disorder or occur as an acquired syndrome. The acquired form of PRCA presents either as an acute self-limited disease, predominantly seen in children, or as a chronic illness that is more frequently seen in adults. It may present as a primary Correspondence: Kenichi Sawada, Department of Internal Medicine III, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. E-mail: ksawada@doc.med.akita-u.ac.jp Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. haematological disorder in the absence of any other disease, or secondary to parvovirus infection, collagen vascular disease, leukaemia, lymphoma, thymoma, solid tumors, treatment with recombinant human erythropoietin (EPO) or other drugs, ABO-incompatible haematopoietic stem cell transplantation and pregnancy. Depending on the cause, the course can be acute and self-limiting or chronic with rare spontaneous remissions (Dessypris, 1988; Dessypris & Lipton, 2004). Primary, or secondary PRCA not responding to treatment of the underlying diseases, is treated as an immunologically- mediated disease, based on a number of studies implicating a pathological role of serum auto-antibodies, natural killer (NK) cell-mediated or T lymphocyte-mediated effects impairing various stages and mechanisms of erythropoiesis as extensively reviewed by Fisch et al (2000). The major objective in the treatment of PRCA is to induce a remission with the recovery of erythropoiesis, thus providing relief from transfusions and avoiding transfusion-associated problems. The therapeutic plan usually focuses on the sequential use of various immu- nosuppressive therapies until a remission is obtained. Remis- sions have been achieved by treatment with corticosteroids (CS), cyclophosphamide (CY), cyclosporine A (CsA), anti- thymocyte globulin (ATG), splenectomy, and plasmapheresis (Dessypris & Lipton, 2004). More recently, the efﬁcacies of the anti-CD20 monoclonal antibody, rituximab (Zecca et al, 2001), and anti-CD52 monoclonal antibody, alemtuzumab (Willis et al, 2001), to induce remissions of therapy-resistant PRCA have also been reported. In general, remission can be easily achieved in the majority of patients. To date, the efﬁcacy of CS, CY and CsA for patients with primary or secondary PRCA has been reported to be between 30–62%, 7–20% and 65–87%, respectively (Clark et al, 1984; Dessypris, 1988; Raghavachar, 1990; Marmont, 1991; Lacy et al, 1996; Mamiya et al, 1997). The efﬁcacy of a combination of CY and CS for refractory patients has been reported to be between 40–60% (Clark et al, 1984; Dessypris, 1988, Mamiya et al, 1997). Since the initial cases were successfully treated by Totterman et al (1984), CsA has established itself as one of the leading drugs for the treatment ª 2008 The Authors First published online 28 May 2008 Journal Compilation ª 2008 Blackwell Publishing Ltd, British Journal of Haematology, 142, 505–514 doi:10.1111/j.1365-2141.2008.07216.x