Responses and Outcome of Immunosuppressive Therapy in Thymoma-Associated Pure Red Cell Aplasia: A Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group.

Abstract

Background: Secondary pure red cell aplasia (PRCA) is associated with various underlying diseases and thymoma accounts for a significant part of secondary PRCA. Thymoma-associated PRCA is generally believed to be an organ-specific autoimmune disease as well as idiopathic form, and immunosuppressive therapy including corticosteroids (CS), cyclophosphamide (CY) and cyclosporine A (CsA) have been proven useful. However, efficacy and long-term outcome of immunosuppressive therapy for secondary PRCA could be distinct among its underlying diseases. Up to the present, the overall long-term response and relapse rates after immunosuppressive therapy in thymoma-associated PRCA are largely unknown.Objectives: We conducted a nationwide survey of immunosuppressive therapy for PRCA in Japan to elucidate the long-term relapse-free survival (RFS) and overall survival (OS) of this disorder. This report is a summary focusing on CsA therapy for thymoma-associated PRCA.Methods: The first questionnaires were sent to 109 medical centers. 273 patients were enrolled from 45 institutions. Secondary questionnaires were sent and the data on 185 patients were collected. 174 patients were eligible for further analysis and we selected 42 of 174 patients (24%) (median age, 64.5 years; range, 26 to 82 years) as thymoma-associated PRCA. Complete remission (CR), partial remission (PR) and no response (NR) were defined as the achievement of normal hemoglobin levels, the presence of anemia but with transfusion-independence and the continued presence of transfusion-dependence, respectively. RFS was estimated as transfusion-free survival without the dose escalation more than 50% of maintenance-dose. Survival was estimated by the Kaplan-Meier method and statistical difference was calculated by the generalized Wilcoxon test.Results. Surgical removal of thymoma was reported in 31 patients, and 17 patients developed PRCA after thymectomy with a median interval of 77 months (range; 1 to 366 months). Five patients underwent surgery without any immunosuppressive therapy after the diagnosis of PRCA, and no patients who achieved response were recognized. The efficacy (CR+PR) of primary treatment was seen in 19 out of 20 patients treated with CsA (95%), 6 out of 14 patients with CS (43%) and 1 of 1 with CY (100%), respectively. Relapse rates in CsA-responders and CS-responders were 0% (median observation period, 18 months) and 50% (34 months), respectively. The RFS in CsA- and CS-responders were significantly different (p=0.018). CsA-responders became independent of blood transfusion within two weeks after starting treatment. The OS did not differ substantially between the CsA- and CS-responders (p=0.663). Most CsA-responders were still on maintenance therapy, and only two patients were alive in CR after stopping therapy.Conclusion: CsA showed an excellent response in thymoma-associated PRCA. However, most patients are still receiving CsA for maintenance therapy. Therefore, other therapeutic modalities may be required to cure this disorder as is the case with idiopathic PRCA.