title: Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration.
abstract: Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newly-diagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day × four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m(2) × 4 rituximab was combined with three 4-day cycles of 28 mg/m(2) (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥ 100 × 10(9)/L) or partial (50-99 × 10(9)/L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50 × 10(9)/L at a median 17 months (range 4-67) projecting 44% event-free survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P<0.01). Adverse events were generally mild-moderate, but 3 patients developed serum sickness and 2 colitis; there were no sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became hypogammaglobulinemic and half had increased frequency of minor infections; 9 of 12 evaluable patients recovered their IgG levels. Rituximab combined with three cycles of dexamethasone provides apparently better results to reported findings with rituximab alone, dexamethasone alone, or the combination with one cycle of dexamethasone. The results suggest medical cure may be achievable in immunothrombocytopenia, especially in women and in patients within two years of diagnosis. (clinicaltrials.gov identifier:02050581).
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA jbussel@med.cornell.edu.
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seery
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Imahiyerobo
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Michaela V
authors.initials: MV
authors.lastname: Thompson
authors.affiliation: Research Triangle Institute, Chapel Hill, NC, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Catellier
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Ithamar G
authors.initials: IG
authors.lastname: Turenne
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA Albert Einstein College of Medicine, MD PhD program, Bronx, NY, USA.
authors.forename: Vivek L
authors.initials: VL
authors.lastname: Patel
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Basciano
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA Genentech, South San Francisco, CA, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Elstrom
authors.affiliation: Departments of Pediatrics and Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA Department of Medicine, Østfold Hospital Trust, Fredrikstad, Norway.
authors.forename: Waleed
authors.initials: W
authors.lastname: Ghanima
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D012189:Retrospective Studies; D000069283:Rituximab; D013156:Splenectomy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003907:Dexamethasone
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