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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

Froissart, Antoine MD; Buffet, Marc MD; Veyradier, Agnès MD, PhD; Poullin, Pascale MD; Provôt, François MD; Malot, Sandrine RN; Schwarzinger, Michael PhD; Galicier, Lionel MD; Vanhille, Philippe MD; Vernant, Jean-Paul MD; Bordessoule, Dominique MD; Guidet, Bertrand MD; Azoulay, Elie MD, PhD; Mariotte, Eric MD; Rondeau, Eric MD; Mira, Jean-Paul MD, PhD; Wynckel, Alain MD; Clabault, Karine MD; Choukroun, Gabriel MD, PhD; Presne, Claire MD; Pourrat, Jacques MD; Hamidou, Mohamed MD; Coppo, Paul MD, PhD

doi: 10.1097/CCM.0b013e31822e9d66
Clinical Investigations

Objective: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura.

Design: 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.

Setting: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France.

Patients: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange.

Intervention: Add-on rituximab therapy, four infusions over 15 days.

Measurements and Main 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.

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From the Service d'Hématologie Clinique et de Thérapie Cellulaire (AF, J-PV), AP-HP, Groupe Hospitalier Pitié-Salpétrière, UPMC Univ Paris 6, Paris, France; Département d'Hématologie (MB, SM, PC), Service de Réanimation Médicale (BG), AP-HP, Hôpital Saint-Antoine, UPMC Univ Paris 6, Paris, France; Service d'Hématologie Biologique (AV), AP-HP, Hôpital Antoine Béclère, Clamart, et U770 INSERM, Université Paris-Sud 11, Le Kremlin-Bicêtre, France; Service d'Hémaphérèse (PP), Hôpital de la Conception, Marseille, France; Service de Néphrologie (FP), Hôpital Albert Calmette, Lille, France; INSERM UMR S 707 (MS), and UPMC, Univ Paris 06, Paris, France; Service d'Immunopathologie (LG), Service de Réanimation Polyvalente (EM, EA), AP-HP, Hôpital Saint-Louis, Université Paris 7 Denis Diderot, Paris, France; Service de Néphrologie (PV), Centre Hospitalier de Valenciennes, Valenciennes, France; Service d'Hématologie Clinique et de Thérapie Cellulaire (DB), CHU Dupuytren, Limoges, France; Service de Néphrologie (ER), AP-HP, Hôpital Tenon, UPMC Univ Paris 6, Paris, France; Service de Réanimation Polyvalente (J-PM), AP-HP, Hôpital Cochin, Université Paris 5, Paris, France; Service de Néphrologie (AW), Hôpital Maison Blanche, Reims, France; Service de Réanimation Médicale (KC), Hôpital Charles Nicolle, Rouen, France; Service de Néphrologie-Médecine Interne (GC, CP), Hôpital Sud, Amiens, France; Service de Néphrologie et Immunologie Clinique (JP), CHU Rangueil, Toulouse, France; Service Médecine Interne A (MH), Hôpital Hôtel-Dieu, Nantes, France.

* See also p. 317.

Supported, in part, by grants from the Etablissement Français du Sang (CS/2002/009) and the GIS-Institut des Maladies Rares (GIS MR0428).

This work was presented at the 50th Annual Meeting of the American Society of Hematology (Abstract #890) and the 2010 Congress of the French Society of Hematology.

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: paul.coppo@sat.aphp.fr

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins