title: Severe refractory autoimmune hemolytic anemia with five-year complete hematologic response to third course of treatment with rituximab: a case report.
abstract: BACKGROUND
  Rituximab is an emerging treatment for autoimmune hemolytic anemia. We report the case of a patient with a five-year complete hematologic response to a third course of treatment with rituximab. Cases of response to rituximab re-treatments have been reported, but none to our knowledge that failed multiple prior treatments and achieved as durable a response.
  
  
  METHODS
  A 45-year-old Hispanic man presented at age 26 with darkening urine and cold intolerance. His blood tests revealed elevated lactic dehydrogenase and bilirubin, a hemoglobin level of 7.4g/dL, and a positive Coombs test for complement C3 and immunoglobulin G antibody. A diagnosis of autoimmune hemolytic anemia was made. After failing multiple therapies including prednisone, splenectomy, immunoglobulin, cyclosporine, danocrine and azathioprine, our patient was treated with a four-week course of rituximab at a dose of 375mg/m2 weekly, 10 years following initial presentation. He achieved a rapid and complete hematologic response that lasted 25 months. Re-treatment with the same course of rituximab prompted a second response that lasted 18 months. A third re-treatment has achieved an ongoing five-year complete hematologic response.
  
  
  CONCLUSIONS
  This is an unusual case of a durable five-year remission of autoimmune hemolytic anemia with rituximab re-treatment following relapse after two prior courses of rituximab and despite the persistence of immunoglobulin G and complement-coated red blood cells. No mechanistic explanations for improved response to rituximab re-treatment in autoimmune hemolytic anemia have been reported in the literature. Future studies of rituximab or other B cell-targeting antibodies in the treatment of autoimmune hemolytic anemia should explore autoantibody immunoglobulin G subclass switching and alterations in complement inhibitory proteins on red blood cell membranes as potential correlates of hematologic response.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Abadie
authors.affiliation: Division of Hematology/Oncology, University of California, 400 Parnassus Ave, Ste 502, San Francisco, CA 94143-0324, USA. khege@celgene.com.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Hege
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D017701:Reticulocyte Count; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006454:Hemoglobins; D007155:Immunologic Factors; D000069283:Rituximab