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 newlydiagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day x 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 x 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 ≥100x10 9 /L) or partial (50-99x10 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 50x10 9 /L at a median 17 months (range 4-67) projecting 44% eventfree 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) Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration
Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed. Six adult and two pediatric patients were identified (six male, two female). Age range at first biopsy was 1-47 (median, 31) years. Underlying diseases included thrombocytopenia-absent radius syndrome, congenital thrombocytopenia with radial-ulnar synostosis, MYH9-related disorder, shortened telomere syndrome, congenital thrombocytopenia with ANKRD26 mutation, and familial platelet disorder with predisposition to acute myeloid leukemia. Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis. Two patients had marrow hypoplasia and two had unremarkable marrow morphology. Three patients-all in the myelodysplastic/myeloproliferative neoplasm-like group-developed disease progression characterized by erythroid and myeloid dysplasia, elevated bone marrow blasts, and new cytogenetic abnormalities. Unlike non-familial myeloid neoplasms, congenital thrombocytopenia patients in the myelodysplastic/myeloproliferative neoplasm-like group had a long and indolent clinical course (average age at disease progression, 47 years). In summary, three distinct morphologic types of congenital thrombocytopenia were identified: a hyperplastic myelodysplastic/myeloproliferative neoplasm-like group, a hypoplastic bone marrow failure-like group, and a group with relatively normal marrow morphology. Emergence of cytogenetic abnormalities and dysplasia in non-megakaryocyte lineages correlated with disease progression.
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