title: [Progression of bone marrow fibrosis with reticulin and collagen hyperplasia during treatment with the thrombopoietin receptor agonist romiplostim in a patient with immune thrombocytopenia].
abstract: Romiplostim is a thrombopoietin (TPO) receptor agonist that has attracted attention as a novel drug for the treatment of refractory immune thrombocytopenia (ITP). However, bone marrow reticulin and collagen fibrosis during the long-term use of romiplostim has recently become a concern. Here, we present a patient with ITP who exhibited bone marrow fibrosis after the completion of a Japanese phase III clinical trial and long-term extension study of romiplostim. The patient was a 64-year-old woman. She was diagnosed with refractory ITP and participated in a clinical trial of romiplostim. Myeloblasts were found in her peripheral blood in Week 116 of treatment with romiplostim in the long-term extension study, and romiplostim was discontinued. In Week 118, teardrop cells appeared and she underwent a bone marrow biopsy. Results showed reticulin and collagen fiber hyperplasia and her platelet count decreased markedly to 0.4×10(4)/μl with macroscopic hematuria. Thereafter, a reduced dose of romiplostim was resumed. Approximately one year after the resumption of romiplostim, a bone marrow biopsy revealed a decrease in reticulin and collagen fibrosis. Although few patients exhibited bone marrow fibrosis with TPO and the event may be reversible, our observations indicate that careful monitoring is required for general clinical use.
authors.affiliation: Department of Hematology/Oncology, University of Yamanashi, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kirito
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
mesh_terms: D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced* / Q000276:immunology; D055728:Primary Myelofibrosis / Q000139:chemically induced* / Q000276:immunology; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D012155:Reticulin / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D013926:Thrombopoietin / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D012155:Reticulin; D013926:Thrombopoietin; C488777:romiplostim