Successful Treatment of Refractory Idiopathic Aplastic Anemia with Rituximab

We report the first case of refractory idiopathic aplastic anemia who responded to Rituximab (anti-CD 20 monoclonal antibody). The patient is a 22 year old Hispanic male construction worker who presented with a two week history of weakness, dyspnea on exertion and gum bleeding was found to have a platelet count of 11 × 10⁹/L, hemoglobin of 7.4 g/dL, and white blood cell count of 1.6 × 10⁹/L with 30% neutrophils. A bone marrow biopsy showed hypocellular marrow with relative lymphocytosis of mixed B and T cells and a normal chromosome analysis. A paroxysmal nocturnal hemoglobinuria (PNH) panel was negative. Serological studies did not show any evidence of HBV, HCV, CMV or EBV infection, but did show previous infection with parvo B19. He was initially treated with horse antithymocyte globulin (ATG) at a dose of 40 mg/kg for four days and cyclosporine. After ten weeks of treatment he was still requiring weekly packed red blood cell and platelet transfusions and G-CSF support. At that time he was treated with rabbit antithymocyte globulin and cyclosporine was continued. He had a partial recovery with absolute neutrophil count remaining mostly above 1 × 10⁹/L, but he was still requiring red blood cell and platelet transfusions with baseline hemoglobin of 6 gm/dL and platelet count of less than 20 × 10⁹/L. A bone marrow biopsy done ten weeks after the rabbit ATG treatment showed hypocellular marrow (20% cellularity) with trilineage hematopoiesis, with no evidence of dysplasia. Due to his transfusion dependence after eight months from his rabbit ATG treatment, he received Rituximab at a dose of 375 mg/m² weekly for four weeks. He had a dramatic improvement of hemoglobin to 11.5 gm/dL and white blood cell count to 3.5 × 10⁹/L, with an absolute neutrophil count of 2 × 10⁹/L, although his platelet count remained at 20 × 10⁹/L. He remains transfusion independent for a follow-up period of 8 months after the Rituximab treatment. Review of literature showed partial to good responses with Rituximab in

1. aplastic anemia patient who refused treatment with ATG and cyclosporine (Hansen PB et al),

2. aplastic anemia associated with CLL (Bharwani L et al),

3. severe aplastic anemia induced by fludarabine and cyclophosphamide in a patient with B-CLL (Castiglioni MG et al) and,

4. refractory Diamond-Blackfan anemia (Morimoto A et al).