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

被引：220

作者：

Froissart, Antoine ^{[2
]}

Buffet, Marc ^{[1
]}

Veyradier, Agnes ^{[4
]}

Poullin, Pascale ^{[5
]}

Provot, Francois ^{[6
]}

Malot, Sandrine ^{[1
]}

Schwarzinger, Michael ^{[7
]}

Galicier, Lionel ^{[8
]}

Vanhille, Philippe ^{[10
]}

Vernant, Jean-Paul ^{[2
]}

Bordessoule, Dominique ^{[11
]}

Guidet, Bertrand ^{[3
]}

Azoulay, Elie ^{[9
]}

Mariotte, Eric ^{[9
]}

Rondeau, Eric ^{[12
]}

Mira, Jean-Paul ^{[13
]}

Wynckel, Alain ^{[14
]}

Clabault, Karine ^{[15
]}

Choukroun, Gabriel ^{[16
]}

Presne, Claire ^{[16
]}

Pourrat, Jacques ^{[17
]}

Hamidou, Mohamed ^{[18
]}

Coppo, Paul ^{[1
]}

机构：

[1] Univ Paris 06, Hop St Antoine, AP HP, Dept Hematol, Paris, France

[2] Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Serv Hematol Clin & Therapie Cellulaire, Paris, France

[3] Univ Paris 06, Hop St Antoine, AP HP, Serv Reanimat Med, Paris, France

[4] Hop Antoine Beclere, AP HP, Serv Hematol Biol, Clamart, France

[5] Hop Conception, Serv Hemapherese, Marseille, France

[6] Hop Albert Calmette, Serv Nephrol, Lille, France

[7] Univ Paris 06, INSERM, UMR S 707, Paris, France

[8] Univ Paris 07, Hop St Louis, AP HP, Serv Immunopathol, Paris, France

[9] Univ Paris 07, Hop St Louis, AP HP, Serv Reanimat Polyvalente, Paris, France

[10] Ctr Hosp Valenciennes, Serv Nephrol, Valenciennes, France

[11] CHU Dupuytren, Serv Hematol Clin & Therapie Cellulaire, Limoges, France

[12] Univ Paris 06, Hop Tenon, AP HP, Serv Nephrol, Paris, France

[13] Univ Paris 05, Hop Cochin, AP HP, Serv Reanimat Polyvalente, Paris, France

[14] Hop Maison Blanche, Serv Nephrol, Reims, France

[15] Hop Charles Nicolle, Serv Reanimat Med, Rouen, France

[16] Hop Sud, Serv Nephrol Med Interne, Amiens, France

[17] CHU Rangueil, Serv Nephrol & Immunol Clin, F-31054 Toulouse, France

[18] Hop Hotel Dieu, Serv Med Interne A, Nantes, France

来源：

CRITICAL CARE MEDICINE | 2012年 / 40卷 / 01期

关键词：

cardiac disorder; coma; hemolytic uremic syndrome; rescue therapy; thrombosis; thrombotic microangiopathy; thrombotic thrombocytopenic purpura; VON-WILLEBRAND-FACTOR; HEMOLYTIC-UREMIC-SYNDROME; FACTOR-CLEAVING PROTEASE; ANTI-ADAMTS13; ANTIBODIES; PROGNOSTIC VALUE; IGG ANTIBODIES; PLATELET COUNT; ADAMTS13; THERAPY; AUTOANTIBODIES;

D O I：

10.1097/CCM.0b013e31822e9d66

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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. (Crit Care Med 2012; 40:104-111)

引用

页码：104 / 111

页数：8

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