Acquired red cell aplasia associated with monoclonal gammopathy of undetermined significance

Pure red cell aplasia (PRCA) is characterized by normocytic normochromic anemia, severe reticulocytopenia, and a total absence or marked reduction of erythroid precursors in the bone marrow. It can be congenital, as in Diamond Blackfan anemia, or acquired. Acquired PRCA is further divided into primary (idiopathic) or secondary. The causes of secondary acquired PRCA include viral infections (Parvovirus B19, HIV, EBV, and CMV), connective tissue disorders (SLE, rheumatoid arthritis), lymphoproliferative disorders (chronic lymphocytic leukemia, Large granular lymphocytic leukemia, Hodgkin & NonHodgkin lymphomas), solid tumors (thymomas, carcinomas), pregnancy, and drugs/toxins [1]. Secondary acquired PRCA due to plasma cell dyscrasias is mostly anecdotal in medical literature with only a few published case reports, mostly in patients with multiple myeloma [2–7] and in even fewer cases associated with monoclonal gammopathy of undetermined significance, MGUS [2,6,8,9]. In a case series that screened for plasma cell dyscrasia in 51 patients initially diagnosed with idiopathic PRCA, 12 patients (24%) were found to have a monoclonal gammopathy – 10 patients with multiple myeloma and two with MGUS [2]. We herein report a case of pure red cell aplasia in a 61-year-old woman with MGUS. The discussion will review the current understanding of the presumed pathogenesis of paraprotein-related PRCA as well as several treatment options that have been proposed. Our patient first presented to her primary care provider (PCP) because of three-week-history of progressive fatigue and dizziness. She has a history of macrocytic anemia of unclear etiology of three years duration, IgG Kappa MGUS, right and left breast cancer diagnosed 13 and 10 years prior respectively, both treated with lumpectomy, radiation therapy, and hormonal therapy, radiation pneumonitis (in remission), and asthma. Her baseline Hemoglobin (Hb) ranged from 10 to 11 g/dL (N 11.5–15.5) with a mean corpuscular volume (MCV) of 107 fL (N 80–100). Monoclonal protein concentration at the time of MGUS diagnosis three years prior was 0.6 gm/dL but no bone marrow biopsy was performed at the time. She is a nonsmoker with no significant history of alcohol use. Review of systems was unrevealing for the possible source (s) of bleeding. A complete blood count (CBC) obtained by her PCP showed severe anemia with a hemoglobin of 3.7 g/dL and she was subsequently sent to a local emergency department (ED). A repeat complete blood count in the ED confirmed a Hb of 3.6 g/dL with an MCV of 102.4 fL, mean cell hemoglobin (MCH) of 36.7 pg (N 27.0–33.0), platelet count of 465 10/mL (N 140–400) and absolute reticulocyte count of 0.01 10/uL (N 0.02–0.08). The white blood cell and differential were within normal limits as were prothrombin time (PT), activated partial thromboplastin time (aPTT), basic metabolic panel and hepatic function panel. The peripheral blood smear showed normochromic normocytic red blood cell morphology. Following transfusion further workup revealed a serum iron of 214 ug/dL (N 50–170), ferritin of 566 ng/mL (N 10–120), vitamin B12 of 1570 pg/mL (N 213–816) and serum folate of 13.6 ng/mL (N 7.0–31.4). Stool for occult blood was negative. The lactate dehydrogenase, haptoglobin, and thyroid stimulating hormone levels were within normal limits. The serum protein electrophoresis was positive for monoclonal proteins at a concentration of 0.3 g/dL. Urine protein electrophoresis and immunofixation were normal as was serumfree kappa to lambda ratio. PCR for Parvovirus B19 DNA was negative. She had an upper endoscopy and colonoscopy, both of which were unremarkable. A bone marrow biopsy revealed normocellular marrow with erythroid hypoplasia, kappa clonal plasma cells (6%) and increased eosinophils (10%). Fluorescence in situ hybridization analysis for myelodysplastic syndrome did not show any abnormalities and the chromosomal analysis revealed normal female karyotype. She was discharged with stable hemoglobin of 9.0 g/dL, having received 5 units of packed red blood cells.