title: A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.
abstract: The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse.
authors: Division of Nephrology, Department of Medicine, Western University, London, ON, Canada.
authors: William F
authors: WF
authors: Clark
authors: Department of Pathology, University of Ottawa, Ottawa, ON, Canada.
authors: Gail
authors: G
authors: Rock
authors: Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors: David
authors: D
authors: Barth
authors: Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: Donald M
authors: DM
authors: Arnold
authors: Division of Hematology and Thromboembolism, Department of Medicine and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: Kathyrn E
authors: KE
authors: Webert
authors: Division of Hematology, Department of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Paul R
authors: PR
authors: Yenson
authors: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: John G
authors: JG
authors: Kelton
authors: Division of Nephrology, Department of Medicine, Western University, London, ON, Canada.
authors: Lihua
authors: L
authors: Li
authors: Division of Clinical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: Steven R
authors: SR
authors: Foley
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab
keywords: ADAMTS13; plasma exchange; rituximab; thrombotic microangiopathy; thrombotic thrombocytopenic purpura