- Eltrombopag Therapy in Children With Rare Disorders Associated With Thrombocytopenia. [Journal Article]
- JPJ Pediatr Hematol Oncol 2019 Jun 12
- Eltrombopag (ELT) is a thrombopoietin receptor activator that has shown efficacy in chronic immune thrombocytopenia. We report the outcome of ELT therapy in 4 children who were treated for rare hemat…
Eltrombopag (ELT) is a thrombopoietin receptor activator that has shown efficacy in chronic immune thrombocytopenia. We report the outcome of ELT therapy in 4 children who were treated for rare hematological disorders, including Pearson syndrome, DiGeorge syndrome, posttransplant allogeneic poor graft function (PGF), and Wiskott-Aldrich syndrome. The ELT tolerance in the analyzed group was good, with the exception of the child with Pearson syndrome, who experienced an exacerbation of cataracts and had to discontinue treatment. Thromboembolic events were observed in one child, who continued ELT therapy despite achieving normalized platelet counts. Independence from PLT transfusions was observed at the 4-week timepoint of therapy in patients with DiGeorge syndrome and PGF who responded to ELT. Discontinuation of therapy was successful in one child, who sustained the normal CBC values afterward. In 2 patients, an increase in neutrophil counts was observed during ELT therapy without additional intervention, and a positive correlation between neutrophil and platelet values during ELT therapy was observed in the child with PGF. ELT is effective in rare pediatric disorders, but response patterns are determined by the underlying disease. ELT shows promising results in patients, but constitutional hematopoiesis defects reduce the chances of a response.
- Eltrombopag: wielding a double-edged sword? [Journal Article]
- BloodBlood 2019 Jun 13; 133(24):2555-2556
- Thrombopoietin Receptor Agonists: Can These Be the Future Answer to the Deadly Thrombocytopenia in Dengue Fever? [Review]
- CCureus 2019 Apr 01; 11(4):e4361
- Dengue is considered the most prevalent mosquito-borne viral disease worldwide and sometimes turns out to be life-threatening. Thrombocytopenia is frequently observed in mild and severe cases of deng…
Dengue is considered the most prevalent mosquito-borne viral disease worldwide and sometimes turns out to be life-threatening. Thrombocytopenia is frequently observed in mild and severe cases of dengue. Severe thrombocytopenia, with a platelet count much below the normal range and hemorrhagic manifestation, is considered a fatal consequence of dengue that needs proper and timely management. The development of the dengue vaccine is quite challenging due to the existence of four different serotypes of the virus. Currently, neither a specific antiviral therapy nor a vaccine is available, and the common treatment modalities include fluid replacement therapy and platelet transfusions. Besides dengue, thrombocytopenia is correlated with many other diseases, particularly immune thrombocytopenic purpura (ITP). Thrombopoietin receptor (TPO-R) agonist, which is responsible for increasing platelet count, is a novel treatment option for chronic ITP patients. At present, two TPO-R agonists - eltrombopag and romiplostim - approved by the US Food and Drug Administration (USFDA) have been successfully used for the treatment of chronic ITP and other thrombocytopenic conditions. However, to date, only a single case study reported the use of romiplostim to enhance the platelet count in a myeloma patient suffering from dengue-associated thrombocytopenia. The objective of this review is to propose to the medical fraternity to consider using these TPO-R agonists to treat dengue hemorrhagic patients with thrombocytopenia and to conduct relevant researches to find out the usefulness of these molecules. This review is completely based on hypotheses and articles showing the positive response with romiplostim in dengue after going through a web-based search on various search engines. Furthermore, this review highlights the need for good-quality, randomized controlled trials and meta-analyses to detect the safety and efficacy of romiplostim and eltrombopag therapy for patients suffering from dengue-related thrombocytopenia.
- Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy. [Journal Article]
- IJInt J Hematol 2019 Jun 10
- Eltrombopag, an oral thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA) and has higher exposure in patients of East Asian origin. We evaluated th…
Eltrombopag, an oral thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA) and has higher exposure in patients of East Asian origin. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with AA refractory or intolerant to immunosuppressive therapy (IST). Twenty-one patients (15 with non-severe AA, six with severe AA) with platelet counts < 30,000/µL received eltrombopag in a dose-escalation fashion (25, 50, 75, or 100 mg once daily) depending on individual platelet responses; the responders continued eltrombopag treatment beyond 6 months. The primary endpoint was hematologic response at 6 months, defined as improvements in blood counts or transfusion requirements. Ten (48%) patients achieved hematologic responses in at least one lineage at 6 months. Six patients achieved tri- and/or bi-lineage responses with continuation of eltrombopag treatment, with two patients no longer requiring eltrombopag treatment. The most common adverse events were nasopharyngitis and abnormal hepatic function, with the majority being grade 1 or 2. Cytogenetic abnormalities were observed in three patients; however, no progression to myelodysplastic syndrome/other malignancy was observed. Eltrombopag can safely restore multi-lineage hematopoiesis in Japanese patients with AA refractory or intolerant to IST.Clinical Trial registration NCT02148133.
- Iron mobilization in a real life cohort of aplastic anemia patients treated with eltrombopag. [Letter]
- AJAm J Hematol 2019 Jun 06
- [Acquired aplastic anemia]. [Journal Article]
- RKRinsho Ketsueki 2019; 60(5):417-422
- Acquired aplastic anemia (AA) is a hematopoietic disorder caused by an immunologic attack on hematopoietic stem cells (HSCs). The presence of cells with a paroxysmal nocturnal hemoglobinuria (PNH) ph…
Acquired aplastic anemia (AA) is a hematopoietic disorder caused by an immunologic attack on hematopoietic stem cells (HSCs). The presence of cells with a paroxysmal nocturnal hemoglobinuria (PNH) phenotype or with copy-number neutral loss of heterozygosity of chromosome 6p (6pLOH) suggests an immune-mediated pathophysiology underlying AA. Recently, genomic studies have revealed clonal hematopoiesis by HSCs with altered genes. PIGA, DNMT3A, ASXL1, BCOR, 6pLOH, and HLA class I allele mutations are common in patients with AA. The genomic landscape of AA is distinct from that of the myelodysplastic syndrome or age-related clonal hematopoiesis. This suggests that escape from an autoimmune attack is strongly associated with clonal hematopoiesis in AA. Eltrombopag (EPAG), a thrombopoietin receptor agonist, has recently emerged as a novel therapeutic agent for AA. Further studies are needed to clarify whether EPAG induces clonal expansion of these clones.
- Eltrombopag: Efficacy and Safety in Steroid Refractory Lupus-Associated Immune Thrombocytopenia. [Journal Article]
- JCJ Clin Rheumatol 2019 Jun 03
- CONCLUSIONS: Eltrombopag is a new drug in our arsenal for treatment of ITP in lupus. It is a rapidly effective, safe, and orally administered medication. It indirectly contributes to reduction in the dose of steroids and immunosuppressants, thereby minimizing their cumulative adverse effects. It is a promising and safe option for the treatment of lupus-associated thrombocytopenia, but this needs further confirmation from multicenter, multiethnic, randomized controlled trials.
- Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. [Review]
- TATher Adv Hematol 2019; 10:2040620719837906
- Primary immune thrombocytopenia (ITP) is a bleeding disorder that conventionally has been treated with steroids or other immunosuppressive treatments. The introduction of thrombopoietin receptor agon…
Primary immune thrombocytopenia (ITP) is a bleeding disorder that conventionally has been treated with steroids or other immunosuppressive treatments. The introduction of thrombopoietin receptor agonists (TPO-RAs), which increase platelet production, dramatically changed the treatment landscape for ITP by providing patients with well-tolerated, long-term treatment options. Two TPO-RAs, eltrombopag and romiplostim, have been approved in the United States and European Union for the treatment of ITP. Some patients do not benefit from the first TPO-RA they receive, so it is assumed that the alternate TPO-RA would have the same outcome. However, eltrombopag and romiplostim have distinct pharmacodynamic and pharmacokinetic properties and may have different tolerability and efficacy in individual patients with ITP. Published retrospective studies showed that >75% of patients who switched to the alternate TPO-RA maintained or achieved a response with the new treatment. Notably, most patients who switched due to lack of efficacy with the first TPO-RA responded to the alternate TPO-RA, which demonstrates an absence of cross-resistance between the two drugs. Therefore, switching to the alternate TPO-RA if the first TPO-RA fails to demonstrate a response should be considered before the use of a less-preferable option.
- Management of acquired aplastic anemia in children : A single center experience. [Journal Article]
- TATransfus Apher Sci 2019 May 10
- Acquired aplastic anemia (AAA) is a rare and potentially life threatening disorder. We retrospectively compared the outcomes of 29 children with AAA who received immunosuppressive therapy (IST) or un…
Acquired aplastic anemia (AAA) is a rare and potentially life threatening disorder. We retrospectively compared the outcomes of 29 children with AAA who received immunosuppressive therapy (IST) or underwent hematopoietic stem cell transplantation (HSCT). Median age at diagnosis was 9.0 years (range, 2-18 years) and median follow-up period was 36 months (range, 3-108 months). Viral infection associated/post hepatitis AAA was in 6 patients (20.6%). According to the initial laboratory findings, 8 patients were classified as very severe AA (vSAA), 8 as severe AA (SAA), and 13 patients as transfusion-dependent moderate AA (MAA). Out of 13, 5 transfusion-dependent MAA patients progressed SAA in median one month (range, 1-5 months), another 6 MAA patients developed remission or became transfusion free during follow-up. Eight patients underwent upfront matched family donor (MFD) HSCT at median 6 months (range, 1-9 months) and achieved complete response (100%). Fifteen cycles of IST were given to 10 (34%) patients lacking MFD at median 3 months (range, 2-6 months). Fifty percent of patients had complete/partial response after IST protocol. Three patients who were unresponsive to IST, proceeded to alternative donor HSCT, in 2nd or 3rd year after the diagnosis and only 1 patient was sustained remission. Several drugs such as mycophenolatemofetil, high-dose cyclophosphamide, levamisole and eltrombopag have been investigated in order to improve the outcome of patients with AAA. Early intervention in AAA patients results in significantly better outcomes.
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- Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). [Journal Article]
- PPlatelets 2019 May 30; :1-4
- Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and/or autoreactive T cells destroy platelets and megakaryocytes in the spleen and bone marrow, respectively. …
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and/or autoreactive T cells destroy platelets and megakaryocytes in the spleen and bone marrow, respectively. Thrombopoietin receptor agonists (TPO-RA e.g. Romiplostim and Eltrombopag) have made a substantial contribution to the treatment of patients with ITP, which are refractory to first-line treatments and approximately 30% demonstrate sustained elevated platelet counts after drug tapering. How TPO-RA induce these sustained responses is not known. We analyzed the efficacy of a murine TPO-RA in a well-established murine model of active ITP. Treatment with TPO-RA (10 ug/kg, based on pilot dose escalation experiments) significantly raised the platelet counts in ITP-mice. Immunomodulation was assessed by measuring serum IgG anti-platelet antibody levels; TPO-RA-treated mice had significantly reduced IgG anti-platelet antibodies despite the increasing platelet counts. These results suggest that TPO-RA is not only an efficacious therapy but also reduces anti-platelet humoral immunity in ITP.