Use of Blood Transfusions In Paroxysmal Nocturnal Hemoglobinuria Patients with and without Aplastic Anemia Enrolled In the Global PNH Registry

Abstract

Abstract 2241 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis which can lead to life-threatening complications including thrombosis, kidney disease, pulmonary hypertension, pain, anemia, and severe fatigue. PNH clones occur in a number of patients with concomitant aplastic anemia (AA) and other bone marrow disorders (BMD). Some patients with PNH and/or BMD may require red blood cell (RBC) transfusions to treat anemia due to hemolysis or bone marrow hypoplasia. Aims: To characterize the use of RBC transfusions among PNH patients with and without underlying AA. Methods: Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry regardless of the proportion of cells with deficiency of glycosylphosphatidyl-inositol anchored proteins (GPI-AP), bone marrow pathology, symptoms, or treatments. Sites collect clinical history at enrollment and additional data every 6 months. Demographic data, use of transfusions and other treatments, lab results, and symptoms are summarized for PNH patients with and without AA. Results: As of June 30, 2010 there were 655 enrolled patients in the Registry (53% female, median age 43). At enrollment, 28% of patients had history of AA and 45% had no history of BMD. Patients with underlying AA had lower median GPI-AP deficient granulocytes than those without BMD (median = 53% vs. 86%, respectively, p Conclusions: A substantial proportion (56%) of patients with PNH, but not all, required at least one transfusion in the year prior to enrolling in the registry, independent of underlying AA. The proportion of patients who had at least one transfusion increased with clone size. Among patients who had at least one transfusion, there was a trend for patients with underlying AA to receive more RBC units than patients without BMD. PNH patients with AA have fewer GPI-AP deficient granulocytes but demonstrate elevated hemolysis similar to patients without history of BMD when patients with similar clone sizes were compared. This Global PNH Registry, which remains open to accrual (pnhregistry@iconplc.com), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment. Disclosures: Schrezenmeier: Alexion Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Brodsky: Alexion Pharmaceuticals, Inc.: Membership on an entity9s Board of Directors or advisory committees. Muus: Celgene: Membership on an entity9s Board of Directors or advisory committees; Alexion: Membership on an entity9s Board of Directors or advisory committees; Amgen: Membership on an entity9s Board of Directors or advisory committees; Novartis: Membership on an entity9s Board of Directors or advisory committees. Bessler: Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity9s Board of Directors or advisory committees; Taligen: Consultancy. Szer: Alexion Pharmaceuticals, Inc.: Membership on an entity9s Board of Directors or advisory committees. Maciejewski: Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Socie: Alexion: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Urbano-Ispizua: Alexion: Membership on an entity9s Board of Directors or advisory committees. Kanakura: Alexion: Membership on an entity9s Board of Directors or advisory committees. Hoechsmann: Alexion: Speakers Bureau. Rosse: Alexion: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Khursigara: Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell: Alexion Pharma International: Employment, Equity Ownership. Bedrosian: Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen: Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.