Pure red cell aplasia with follicular lymphoma showing regression and progression parallel to lymphoma

Abstract

Malignant lymphomas occasionally accompany autoimmune diseases. Pure red cell aplasia (PRCA) is thought to arise via an autoimmune mechanism and rarely occurs in lymphoma. Here, we report a case of follicular lymphoma accompanying PRCA, in which lymphoma and PRCA showed parallel regression and progression in response to chemotherapy for lymphoma. An 83-year-old Japanese man presented with a chief complaint of dizziness. He was found to be anemic, and had a gastric ulcer and retroperitoneal mass. Biopsy of the gastric lesion suggested malignant lymphoma, and he was referred to our hospital. The initial laboratory results were as follows: hemoglobin, 73 g/L; mean corpuscular volume, 92.6 fL; and reticulocyte count, 2 9 10/L. Computed tomography (CT) imaging showed general lymphadenopathy, and excision biopsy of the axillary lymph node confirmed grade 1 follicular lymphoma. Fluorescence in situ hybridization (FISH) analysis of the lymph node was positive for fusion of the Bcl-2 and IgH genes. Bone marrow examination showed no lymphoma infiltration. He received six courses of R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone) chemotherapy and complete response was achieved. Even after completion of chemotherapy, his anemia persisted and he required regular transfusion of red blood cells. White blood cell and platelet counts were normal. Bone marrow examination showed remarkable erythroid hypoplasia without dysplasia, and lymphoma infiltration was not detected by FISH analysis. CT imaging indicated that thymoma was absent. Hemolytic anemia was unlikely, as lactic dehydrogenase, bilirubin, and haptoglobin were normal. The patient further did not show indications of thymoma or hemolytic anemia in his clinical course. Nine months after completion of chemotherapy, his anemia spontaneously resolved and he no longer required transfusions. Approximately 2 years after the initial therapy, CT imaging showed enlarged abdominal lymph nodes and the patient was diagnosed with recurrent lymphoma. He was observed without therapy, and 1 year after the recurrence, the disease gradually progressed accompanied by concomitant progression of anemia. At initiation of salvage therapy, hemoglobin was 82 g/L and reticulocyte count was 5 9 10/L. Bone marrow examination again showed erythroid hypoplasia without dysplasia or infiltration of lymphoma. Immunoglobulin M (IgM) antibody to parvovirus B19 was negative. With modified R-ESHAP chemotherapy (rituximab, etoposide, methylprednisolone, cytarabine, and carboplatin), his lymphoma achieved partial response. His anemia also improved; hemoglobin was 100 g/L and reticulocyte count was 85 9 10/L. However, as he suffered severe discitis, he could not continue chemotherapy. His lymphoma grew slowly, and his anemia progressed again. Bone marrow examination showed neither dysplasia nor infiltration of lymphoma. Rituximab mono-therapy was ineffective for lymphoma and anemia. Seven months after salvage chemotherapy, at the time of this report, the patient is alive with slowly progressive lymphoma and red blood cell transfusion dependence. His clinical course is shown in Fig. 1. PRCA has been reported to occur rarely in lymphoma [1–4]. In most reported cases, PRCA improved after the chemotherapy for lymphoma. However, steroids and other immunosuppressive agents, such as cyclophosphamide [5] and rituximab [6], used for lymphoma therapy are also G. Yamamoto H. Maki M. Ichikawa M. Kurokawa (&) Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: kurokawa-tky@umin.ac.jp