Pure red cell aplasia associated with hemolytic anemia refractory to standard measures and resolved by rituximab in an elderly patient

Abstract

Acquired pure red cell aplasia (PRCA) simultaneously associated with autoimmune hemolytic anemia (AIHA) has been very rarely described so far [1, 2]. We describe the case of an elderly woman, who was diagnosed as having idiopathic PRCA associated with AIHA which was unresponsive to two lines of immunosuppressive treatment and was then resolved by rituximab given as salvage therapy. A 68-year-old woman kept under our attention because of severe malaise, pallor and fatigue. Her past medical history was unremarkable; in particular, she denied any personal or familiar history of hereditary hemolytic anemia or autoimmune diseases. A past blood count had shown normal hemoglobin. Physical examination at admission was unremarkable, with the exception of pallor and mild jaundice; the patient did not present either spleen or liver enlargement. A comprehensive laboratory evaluation revealed no abnormalities other than those related to anemia and hemolysis. Indeed, severe normochromic and normocytic anemia (hemoglobin, Hb = 2.7 g/dl) was revealed. Reticulocytes were not detectable; white blood cell and platelet counts were normal. Increased indirect serum bilirubin, urinary urobilinogen and serum lactate dehydrogenase were present; serum haptoglobin was undetectable. Direct and indirect Coombs tests were positive. A warm-reactive antibody of the IgG isotype was eluted from the red blood cells (RBC). Serologic tests for parvovirus B19, HIV, Hepatitis virus, human cytomegalovirus, and Epstein-Barr virus were negative. Moreover, no clinical and/or laboratory signs of associated autoimmune disease were detected. Chest X-ray and total body CT scan showed normal findings. On the blood film, spherocytes and polychromasia were found. A bone marrow (BM) aspirate and a trephine biopsy demonstrated normal representation of myeloid and megakaryocytic precursors, but nearly absent erythroid precursors. Based on these findings, a diagnosis of AIHA combined to PRCA was made. Given the symptomatic anemia and the very low Hb levels, the patient received repeated administration of RBC concentrates. Methylprednisolone 2 mg/kg was given for 4 weeks without any benefit; equally ineffective was the concomitant treatment with cyclosporine-A (CSA) during the following 4 weeks. Therefore, in the light of reported experiences concerning the treatment of AIHA [3] and PRCA [2], the patient was offered rituximab as salvage therapy for which she gave her informed consent. Rituximab was administered intravenously at the dose of 375 mg/m as a 4-h infusion, once weekly for a total of four doses, without any adverse reaction or side effects (July 2007). Progressive increase of Hb levels and achievement of transfusion independence followed the rise in reticulocytes after the fourth dose of rituximab. Serum hemolytic parameters normalized, as well as the serologic finding of an auto-antibody also disappeared. A BM aspirate demonstrated no abnormal findings and, in particular, the full recovery of the erythroid matrix. The patient, 10 months after rituximab therapy, shows normal Hb and reticulocyte levels, and she is no longer received immunosuppressive therapy. Treatment of PRCA and of AIHA usually employs immunosuppressive drugs, mainly steroids and CSA, or immunomodulating agents [1]. However, conventional immunosuppressive treatments are often unsatisfactory for which rituximab has been successfully used as salvage therapy in the pediatric setting [2]. Our L. Scaramucci (&) P. Niscola M. Ales M. Giovannini A. Tendas L. Cupelli A. Siniscalchi D. Piccioni T. Dentamaro A. Perrotti P. de Fabritiis Hematology Unit, Sant’Eugenio Hospital, Piazzale dell’Umanesimo 10, 00144 Rome, Italy e-mail: scaramucci.laura@gmail.com