title: Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria.
abstract: BACKGROUND
  Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and the subsequent production of blood cells with a deficiency of surface proteins that protect the cells against attack by the complement system. We tested the clinical efficacy of eculizumab, a humanized antibody that inhibits the activation of terminal complement components, in patients with PNH.
  
  
  METHODS
  Eleven transfusion-dependent patients with PNH received infusions of eculizumab (600 mg) every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12. Clinical and biochemical indicators of hemolysis were measured throughout the trial.
  
  
  RESULTS
  Mean lactate dehydrogenase levels decreased from 3111 IU per liter before treatment to 594 IU per liter during treatment (P=0.002). The mean percentage of PNH type III erythrocytes increased from 36.7 percent of the total erythrocyte population to 59.2 percent (P=0.005). The mean and median transfusion rates decreased from 2.1 and 1.8 units per patient per month to 0.6 and 0.0 units per patient per month, respectively (P=0.003 for the comparison of the median rates). Episodes of hemoglobinuria were reduced by 96 percent (P<0.001), and measurements of the quality of life improved significantly.
  
  
  CONCLUSIONS
  Eculizumab is safe and well tolerated in patients with PNH. This antibody against terminal complement protein C5 reduces intravascular hemolysis, hemoglobinuria, and the need for transfusion, with an associated improvement in the quality of life in patients with PNH.
authors.affiliation: Department of Haematology, Leeds Teaching Hospitals National Health Science Trust, Leeds, United Kingdom. peter.hillmen@panp-tr.northy.nhs.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Claire
authors.initials: C
authors.lastname: Hall
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Marsh
authors.forename: Modupe
authors.initials: M
authors.lastname: Elebute
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bombara
authors.forename: Beth E
authors.initials: BE
authors.lastname: Petro
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Cullen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Richards
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rollins
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Mojcik
authors.forename: Russell P
authors.initials: RP
authors.lastname: Rother
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017707:Erythrocyte Transfusion; D005260:Female; D006456:Hemoglobinuria / Q000175:diagnosis / Q000188:drug therapy; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy* / Q000628:therapy / Q000652:urine; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D017701:Reticulocyte Count; D016482:Urinalysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab; D007770:L-Lactate Dehydrogenase