title: Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic anemia.
abstract: OBJECTIVE
  To evaluate the sustained response to low-dose (LD) rituximab in autoimmune hemolytic anemia (AIHA), the ex vivo effect on anti-RBC antibody production by mitogen-stimulated direct antiglobulin test (MS-DAT), and the in vitro dose effect of the drug on the production of anti-RBC antibodies.
  
  
  METHODS
  Thirty two patients, 18 warm (W) AIHA and 14 cold hemagglutinin disease (CHD), were treated with LD rituximab (100 mg fixed dose ×4 weekly infusions) along with a short course of oral prednisone. Complete clinical examination, blood counts, and hemolytic markers were performed at enrollment and at month 6, 12, 24, and 36.
  
  
  RESULTS
  Hematological parameters significantly improved at all time points compared to enrollment. The overall response was 90%, 100%, 100%, and 89% and the relapse-free survival 87%, 79%, 68%, and 68% at 6, 12, 24, and 36 months, respectively. Response rates were slightly better in WAIHA than in CHD, and relapse risk was greater in cold than warm forms (HR 2.1, 95% CI 0.6-7.9). Four patients were retreated (one patient twice), all achieving a response, lasting a median of 18 months (range 9-30). Treatment was well tolerated without adverse events or infections. Anti-RBC antibody production by MS-DAT significantly decreased over time. In vitro studies showed that rituximab effectively inhibited anti-RBC antibody production at 50 μg/mL, 1/6 of the drug concentration after therapy with standard doses.
  
  
  CONCLUSIONS
  These data confirm that LD rituximab treatment is effective and induces sustained responses in AIHA, and that a lower dose of the drug is enough to down-regulate autoantibody production.
authors.affiliation: U.O. Ematologia e CTMO, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.forename: Anna
authors.initials: A
authors.lastname: Zaninoni
authors.forename: Francesca Guia
authors.initials: FG
authors.lastname: Imperiali
authors.forename: Eros
authors.initials: E
authors.lastname: Di Bona
authors.forename: Bruno
authors.initials: B
authors.lastname: Fattizzo
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanella
mesh_terms: D000328:Adult; D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab
keywords: autoimmune hemolytic anemia; cold hemagglutinin disease; rituximab