Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis leading to anemia and other clinical manifestations. Transfusions are often required to support hemoglobin at tolerable levels. A PNH patient with aplastic anemia was treated with the complement inhibitor eculizumab, followed by concurrent treatment with recombinant human erythropoietin (rHuEpo). Eculizumab alone reduced hemolysis, increased PNH red blood cell (RBC) mass, and decreased transfusions. Addition of rHuEpo during eculizumab therapy, enhanced erythropoiesis, further increased PNH RBC mass and hemoglobin levels, and rendered the patient transfusion independent for more than two years. These data show that driving erythropoiesis during eculizumab treatment provided further benefit to a patient with PNH and underlying bone marrow failure.Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder resulting from clonal expansion of a hematopoietic stem cell containing a somatic mutation of the PIG-A gene, which results in a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins from the surface of red blood cells (RBCs).1 Absence of the GPI-anchored terminal complement inhibitor CD59 on RBCs results in an increase in complement-mediated RBC lysis leading to anemia and other clinical manifestations of the disease.2–5 Currently, no approved therapies effectively reduce intravascular hemolysis in PNH, and patients are often dependent on transfusions to artificially support hemoglobin levels.2
Eculizumab is a novel humanized monoclonal antibody directed against the complement protein C5.6 Eculizumab was previously shown to safely and effectively reduce intravascular hemolysis and transfusion requirements in patients with PNH.7–9 Herein, we report a case study of a PNH patient with evidence of underlying aplastic anemia who was treated with eculizumab and thereafter received recombinant human erythropoietin (rHuEpo) in an effort to increase PNH RBC production during complement inhibition and thereby further reduce transfusion requirements.
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