Long-Term Relapse-Free Survival and Overall Survival of Patients with Acquired Primary Idiopathic Pure Red Cell Aplasia Receiving Cyclosporine: A Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group.

Background: The efficacy of corticosteroids (CS), cyclophosphamide (CY) and cyclosporine (CsA) for the patients with primary or secondary pure red cell aplasia (PRCA) is between 30–56%, 7–20% and 75–87%, respectively. Although it is evident that the efficacy of CsA is the highest amongst these three drugs, CsA has remained second to third-line therapy largely because the long-term relapse-free survival (RFS) and overall survival (OS) after CsA therapy are unknown. Objectives: We conducted a nationwide survey of immunosuppressive therapy for PRCA in Japan to elucidate the long-term RFS and OS of CsA therapy for acquired primary idiopathic (API-) PRCA. Methods: Questionnaires were sent to 109 medical centers. From 1990 through 2006, we identified 174 adult patients with acquired PRCA. The underlying diseases could affect RFS and OS of immunosuppressive therapy. We, therefore, selected 64 patients (38%, median age, 56 years; range, 18 to 89 years) with API-PRCA according to the classification proposed by Dessypris and Lipton. Complete remission (CR), partial remission (PR) and no response (NR) was 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 and qui square test. Results: The efficacy (CR+PR) of primary treatment was seen in 24 of 32 patients treated with CsA (75%), 16 of 26 patients with PSL (62%), 0 of 3 patients with CY (0%), 0 of 1 patient with anabolic steroid and was undetermined in 2 patients because of short observation periods (<1 week). Overall, 60 of 64 API-PRCA patients (94%) responded to primary or subsequent immunosuppressive therapy, and 41 and 15 patients were maintained CsA±CS (CsA-responders) or CS alone (CS-responders), respectively. The median RFS in CsA-responders was 52 months and longer than that seen in CS-responders (16 months) (p<0.01), in the median follow-up period of 36 and 8 months, respectively. In CsA-responders, three patients died due to renal failure, liver failure associated with hepatitis C infection and infection after transformation to aplastic anemia. However, overall survival was not significantly different between the two groups (p=0.104). In CsA-responders, the cease of maintenance therapy was strongly correlated with relapse (p<0.001). Eleven of 14 patients relapsed with a median interval of 10 months after discontinuing CsA (range 1.5 to 40 months), whereas only 4 of 27 patients relapsed during maintenance therapy. Conclusions: We, for the first time, demonstrated that CsA ensures prolonged PFS than CS in API-PRCA. However, most patients are still receiving CsA for maintenance therapy. Therefore, other therapeutic modalities may be required to cure API-PRCA.