title: A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura.
abstract: The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 10(9)/L and 38% > 150 × 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.
authors.affiliation: Department of Haematology, University College London Hospital, London, United Kingdom. m.scully@ucl.ac.uk
authors.forename: Marie
authors.initials: M
authors.lastname: Scully
authors.forename: Vickie
authors.initials: V
authors.lastname: McDonald
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.forename: Beverley J
authors.initials: BJ
authors.lastname: Hunt
authors.forename: Ian
authors.initials: I
authors.lastname: Longair
authors.forename: Hannah
authors.initials: H
authors.lastname: Cohen
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D051722:ADAM Proteins / Q000276:immunology; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D012008:Recurrence; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D007155:Immunologic Factors; D000069283:Rituximab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human