Acquired Pure Red Cell Aplasia Associated with Malignant Lymphomas: A Nationwide Cohort Study in Japan
Authors: Hirokawa Makoto , Sawada Ken-ichi , Fujishima Naohito , Kawano Fumio , Kimura Akiro , Watanabe Takashi , Arai Ayako , Matsui Toshimitsu , Nakao Shinji , Urabe Akio , Omine Mitsuhiro , Ozawa Keiya 
Published: April 2020

Abstract
Pure red cell aplasia (PRCA) has been reported in association with lymphoma as one of the autoimmune diseases seen during the course of lymphoid malignancies. However, the relation of PRCA with the underlying lymphomas remains unclear. The aim of this study was to clarify the histologic subtypes of lymphomas, the chronological sequence of anemia and lymphoma, and the response to treatment, and eventually to establish the treatment guideline for lymphoma-associated PRCA. We conducted a nationwide survey in Japan. From a cohort of 185 patients with PRCA, 8 patients with lymphoma were evaluated. Complete response (CR), partial response (PR) and no response (NR) were defined as the achievement of normal hemoglobin levels without transfusion, the presence of anemia but without transfusion dependence, and the continued presence of transfusion-dependence, respectively. Patient age at the onset of PRCA ranged from 48 to 82 years (median age, 68 years) with an equal male to female ratio. Histologic subtypes varied and the lymphoma was of the B-cell type in four cases and of the T-cell type in four. Four patients had coexisting anemia and lymphoma. One patient developed PRCA before the onset of lymphoma. Three other patients developed PRCA following lymphoma, two of whom developed anemia during remission. Anemia responded to chemotherapy and/or immunosuppressive therapy in seven of eight patients. In four responding patients, PRCA remained in durable remission without maintenance immunosuppressive therapy (27, 76, 97 and 127 months), which is a different feature from that of idiopathic PRCA (Sawada K, et al. Haematologica2007;92:1021). Four patients were alive, and two of these four remained in remission for both lymphoma and PRCA. Effective chemotherapy was associated with remission of anemia in patients with concurrent lymphoma and PRCA. In patients with PRCA presenting before or after the onset of lymphoma, immunosuppressive therapy was effective for improving anemia. In conclusion, chemotherapy should be introduced for patients with coexisting lymphoma and PRCA. Additional immunosuppressive therapy may be necessary for PRCA that has failed to respond to chemotherapy. Durable maintenance-free remission of anemia may be obtained in lymphoma-associated PRCA.
Table 1. Patient characteristics and induction therapy for PRCA
Age/Sex Histologic subtypes Days from lymphoma to PRCA Disease status of lymphoma Induction therapy for PRCA * Response of PRCA Response of lymphoma *(/), in sequential administration; (-), in combination. 76/F DLBCL −114 - Steroid CR - 75/M DLBCL −13 On disease R-CHOP/CsA NR/CR PR 62/M ATLL 0 On disease CHOP-CsA CR PD 82/F MZL 0 On disease Steroid NR NR 58/F AILT 35 On disease CHOP CR CR 48/M Follicular 720 On disease Steroid/CHOP NR/CR CR 64/M T-LBL 205 CR Steroid PR - 71/F AILT 801 CR Steroid/CsA PR/PR -