ABSTRACT
BACKGROUND: We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm(3) within the first 12 weeks. These patients were followed for the next year. METHODS: Platelet counts were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. RESULTS: Eight of the 11 initial responders maintained a platelet count over 150,000/mm(3) without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm(3) without the need for further intervention. CONCLUSIONS: Rituximab resulted in sustained efficacy with platelet counts of 50,000/mm(3) or higher in 11 of 36 patients (31%).
Subject(s)
Antibodies, Monoclonal/administration & dosage , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Adolescent , Antibodies, Monoclonal, Murine-Derived , Child , Child, Preschool , Chronic Disease , Female , Follow-Up Studies , Hemorrhage , Humans , Infant , Male , Platelet Count , Recurrence , Remission Induction , RituximabABSTRACT
We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50,000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.
Subject(s)
Antibodies, Monoclonal/toxicity , Antibodies, Monoclonal/therapeutic use , Immunologic Factors/toxicity , Immunologic Factors/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Adolescent , Antibodies, Monoclonal, Murine-Derived , Child , Child, Preschool , Humans , Hypotension/chemically induced , Patient Selection , Prospective Studies , Rituximab , Serum Sickness/chemically induced , Treatment OutcomeABSTRACT
The possibility of concomitant immunity and its potential mechanisms in Onchocerca volvulus infection were examined by analyzing cytokine and antibody responses to infective larval (third-stage larvae [L3] and molting L3 [mL3]), adult female worm (F-OvAg), and skin microfilaria (Smf) antigens in infected individuals in a region of hyperendemicity in Cameroon as a function of age. Peripheral blood mononuclear cell interleukin 5 (IL-5) responses to F-OvAg and Smf declined significantly with age (equivalent to years of exposure to O. volvulus). In contrast, IL-5 secretion in response to L3 and mL3 remained elevated with increasing age. Gamma interferon responses to L3, mL3, and F-OvAg were low or suppressed and unrelated to age, except for responses to Smf in older subjects. IL-10 levels were uniformly elevated, regardless of age, in response to L3, mL3, and F-OvAg but not to Smf, for which levels declined with age. A total of 49 to 60% of subjects had granulocyte-macrophage colony-stimulating factor responses to all O. volvulus antigens unrelated to age. Analysis of levels of stage-specific immunoglobulin G3 (IgG3) and IgE revealed a striking, age-dependent dissociation between antibody responses to larval antigens (L3 and a recombinant L3-specific protein, O. volvulus ALT-1) which were significantly increased or maintained with age and antibody responses to F-OvAg, which decreased. Levels of IgG1 to L3 and F-OvAg were elevated regardless of age, and levels of IgG4 increased significantly with age, although not to O. volvulus ALT-1, which may have unique L3-specific epitopes. Immunofluorescence staining of whole larvae showed that total anti-L3 immunoglobulin levels also increased with the age of the serum donor. The separate and distinct cytokine and antibody responses to adult and infective larval stages of O. volvulus which are age related are consistent with the acquisition of concomitant immunity in infected individuals.
