title: Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center.
abstract: OBJECTIVE
  To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura.
  
  
  METHODS
  Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine.
  
  
  METHODS
  Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France.
  
  
  METHODS
  Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange.
  
  
  METHODS
  Add-on rituximab therapy, four infusions over 15 days.
  
  
  RESULTS
  One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred.
  
  
  CONCLUSIONS
  Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, AP-HP, Groupe Hospitalier Pitié-Salpétrière, UPMC Univ Paris 6, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Froissart
authors.forename: Marc
authors.initials: M
authors.lastname: Buffet
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.forename: François
authors.initials: F
authors.lastname: Provôt
authors.forename: Sandrine
authors.initials: S
authors.lastname: Malot
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzinger
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Eric
authors.initials: E
authors.lastname: Mariotte
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Alain
authors.initials: A
authors.lastname: Wynckel
authors.forename: Karine
authors.initials: K
authors.lastname: Clabault
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourrat
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy*; D000069283:Rituximab; D016879:Salvage Therapy; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab