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      Persistent Anemia in a Patient with Diffuse Large B Cell Lymphoma: Pure Red Cell Aplasia Associated with Latent Epstein-Barr Virus Infection in Bone Marrow


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          We report a case of pure red cell aplasia (PRCA), which was initially suspected as a result of bone marrow involvement of diffuse large B cell lymphoma. Persistent anemia without an obvious cause was observed in a 47-yr-old man diagnosed with relapsed diffuse large B cell lymphoma. The bone marrow study showed only erythroid hypoplasia without the evidence of bone marrow involvement with lymphoma cells, thus PRCA was suggested. However, parvovirus infection was excluded as a potential cause of PRCA because of negative IgM anti-parvovirus B19 antibody and negative parvovirus PCR in the serum. Latent Epstein-Barr virus (EBV) infection of bone marrow was suggested by in situ hybridization with EBV-encoded small RNA (EBER) that showed a strong positive expression in bone marrow cells. Thus, PRCA was thought to be associated with latent EBV infection in bone marrow cells. Although the finding of unexplained anemia is a possible predictor of bone marrow involvement with lymphoma cells, PRCA as a result of a viral infection including EBV should be considered in lymphoma patients. This is the first report of the occurrence of PRCA associated with latent EBV infection in a patient with non-Hodgkin's lymphoma.

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          Pure red cell aplasia due to parvovirus following treatment with CHOP and rituximab for B-cell lymphoma.

          A 26-year-old woman, diagnosed with diffuse large B-cell lymphoma, was treated with CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone), rituximab and radiotherapy. She developed transfusion-dependant anaemia, which persisted following chemotherapy. Bone marrow aspirate and biopsy were consistent with pure red cell aplasia and parvovirus infection. Serology was negative for previous or acute infection but parvovirus DNA was detected by polymerase chain reaction. Administration of intravenous immunoglobulin (1 g/kg) resulted in reticulocytosis and recovery of her haemoglobin. We hypothesize that rituximab caused depletion of her normal B cells, resulting in an inability to mount a primary immune response to parvovirus infection.
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            Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab.

            Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.
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              Pure red cell aplasia--a rare disease with multiple causes.

              Pure red cell aplasia (PRCA) is a relatively rare disease although multiple factors are implied in the pathogenesis of its development. A slow progressive normocytic-normochromic anemia and reticulocytopenia, without leukopenia and thrombocytopenia in a patient who, except pallor, does not show abnormal findings on physical examination, should arise the suspicion that he has PRCA. Search for underlying diseases or infections and intake of drugs may help for the establishment of the diagnosis of acquired PRCA. Lack of erythroblasts in the bone marrow with normal development of the other hemopoietic series, as well as high level of serum erythropoietin are important clues for the diagnosis. Elimination of potentially causative factors, administration of immunosuppressive agents and/or recombinant erythropoietin, preferably epoetin beta, may induce remission and complete recovery.

                Author and article information

                J Korean Med Sci
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                September 2007
                30 September 2007
                : 22
                : Suppl
                : S167-S170
                Division of Hematology and Oncology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea.
                [* ]Department of Pathology, Korea University Medical Center, Seoul, Korea.
                []Department of Laboratory Medicine, Korea University Medical Center, Seoul, Korea.
                []Department of Laboratory Medicine, Hallym University Chunchon Sacred Heart Hospital, Chunchon, Korea.
                Author notes
                Address for correspondence: Seok Jin Kim, M.D. Division of Oncology and Hematology, Department of Internal Medicine, Korea University Medical Center, 126-1 Anamdong 5-ga, Seongbuk-gu, Seoul 136-705, Korea. Tel: +82.2-920-6722, Fax: +82.2-920-6520, kstwoh@ 123456korea.ac.kr
                Copyright © 2007 The Korean Academy of Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 13 July 2006
                : 06 November 2006
                Case Report

                lymphoma,red-cell aplasia,epstein-barr virus
                lymphoma, red-cell aplasia, epstein-barr virus


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