title: Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria.
abstract: BACKGROUND
  Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, hematopoietic stem cell disorder that manifests with hemolytic anemia and bone marrow failure. Eculizumab has been shown to improve anemia, decrease intravascular hemolysis, and reduce the risk of thrombosis.
  
  
  METHODS
  This is a retrospective, single-center study of patients treated with eculizumab and categorized according to response criteria. Complete response (CR) was defined as transfusion independence with normal hemoglobin for age/sex, absence of symptoms, and lactate dehydrogenase <1.5 times the upper limit of normal. A good partial response (GPR) was defined as decreased transfusions from pretreatment and lactate dehydrogenase <1.5 upper limit of normal without thrombosis. These patients did not achieve normal hemoglobins for age and sex. A suboptimal response was defined as unchanged transfusion needs and persistent of symptoms.
  
  
  RESULTS
  Thirty patients with PNH clones were treated with eculizumab and classified as complete responders (four patients), good partial responders (16), and suboptimal responders (10) over 863 patient-months of treatment. Complete responders had a decrease in red cell clone size, while good partial responders had an increase. Thirteen patients treated did not meet inclusion criteria for the clinical trials of eculizumab due to lack of transfusions or thrombocytopenia; eight had at least a GPR.
  
  
  CONCLUSIONS
  Eculizumab is efficacious in patients with PNH, but responses can vary and may depend on underlying marrow failure, underlying inflammatory conditions and red cell clone size following treatment. Normalization of hemoglobin with decrease in red cell clone size may predict CR.
authors.affiliation: Division of Hematology, Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.forename: Donna
authors.initials: D
authors.lastname: Dorr
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; C481642:eculizumab