Scientific Letter
Safety and efficacy of the use of eltrombopag in a case of severe acquired bone marrow aplasia
Eficacia y seguridad en el uso del eltrombopag en un caso de aplasia medular adquirida grave
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(b) Peripheral blood platelet count from initiation of eltrombopag to present.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acquired bone marrow aplasia is a disorder with an estimated incidence of 1–2 cases per million inhabitants per year<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> characterised by low bone marrow cellularity that results in pancytopaenia. The first-line treatment in children is matched related donor haematopoietic stem cell transplantation (HSCT), and if this option is not available, immunosuppressive therapy<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>; should the latter fail, the next step is matched unrelated donor HSCT. Eltrombopag, a thrombopoietin analogue, has been recently introduced as a possible treatment of refractory aplasia. There is published evidence of its effectiveness in adults, but its role in paediatric patients has yet to be evaluated.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a girl aged 11 years with severe acquired bone marrow aplasia whose test results showed trilineage peripheral blood recovery after starting treatment with eltrombopag.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient initially presented with generalised ecchymosis and petechiae, asthenia and metrorrhagia of 15 days’ duration. The blood panel revealed severe pancytopaenia with findings suggestive of hyporegenerative anaemia (haemoglobin, 7.6<span class="elsevierStyleHsp" style=""></span>g/dL; reticulocytes, 0.69%), a platelet count of 8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1000/μL and a neutrophil count of 0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1000/μL, with no abnormalities in blood chemistry or findings suggestive of haemolysis or coagulopathy. There was no excess of blasts in the peripheral blood smear and serology tests were negative. The patient underwent bone marrow aspiration and biopsy, the findings of which were compatible with severe bone marrow aplasia. We ruled out paroxysmal nocturnal haemoglobinuria, and the chromosome fragility test was negative.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Since the patient did not have an HLA-matched relative, she started immunosuppressive therapy with thymoglobulin and ciclosporin combined with granulocyte-colony stimulating factor (G-CSF). The initial response was good, and the patient showed a favourable partial response at day 60 of treatment. She later exhibited progressive deterioration, and by day 120 the findings of the evaluation were consistent with a nonresponder profile, with the patient requiring weekly transfusions. Due to the failure of immunosuppressive therapy, the patient was considered eligible for unrelated-donor HSCT given the lack of a related donor. After an unsuccessful search for a potential donor that lasted 6 months, given the severity of her bone marrow aplasia, the decision was made to initiate treatment with eltrombopag with a dose of 50<span class="elsevierStyleHsp" style=""></span>mg administered orally every 24<span class="elsevierStyleHsp" style=""></span>h. The laboratory tests at 3 weeks already evinced a trilineage response, and from week 7, sustained levels of haemoglobin of 12<span class="elsevierStyleHsp" style=""></span>g/dL and sustained counts of at least 50<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>platelets/μL and at least 1500<span class="elsevierStyleHsp" style=""></span>neutrophils/μL. On week 15 we started tapering off the dose of ciclosporin, which was eventually discontinued on week 44 with no evidence of an impact on cell counts.</p><p id="par0025" class="elsevierStylePara elsevierViewall">At present, after 16 months of treatment with eltrombopag at a dose of 50<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, 5 of them as monotherapy, the follow-up bone marrow workup shows mildly low counts with increased counts of all haematopoietic stem cell lineages compared to previous evaluations. Peripheral blood values remained stable (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient has not exhibited any adverse effects at any point during the follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Acquired idiopathic bone marrow aplasia is the most frequent form of aplasia in children. In severe cases, like the one presented here, it can be life-threatening due to the risk of haemorrhage and infection, and it is essential that optimal treatment is initiated early. In our patient, management started with the first-line treatment, consisting of a combination of thymoglobulin and ciclosporin,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> but she turned out to be part of the 30% of patients that do not respond to this therapy. Several approaches have been tried in this group of patients. The first clinical trial of eltrombopag for treatment of bone marrow aplasia was conducted by Olnes et al. in 2012 in adult patients. Subsequent trials have corroborated the beneficial role of this thrombopoietin analogue in increasing the counts of not only platelets, but also the three lineages of peripheral blood cells<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> in adult patients with bone marrow aplasia. In the paediatric population, clinical trials of eltrombopag have only been performed in patients with chronic primary immune thrombocytopaenia<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> or with failure of platelet recovery following HSCT,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> with favourable outcomes in both. The current literature does not offer any data of its use in children with idiopathic bone marrow aplasia.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The case presented here is relevant because it is the first to illustrate the effectiveness of this drug in the treatment of paediatric bone marrow aplasia, with a sustained cellular response that persisted after one year of treatment. We ought to highlight that we found no evidence of adverse effects in the 16-month follow-up, although this time frame was too short to assess long-term toxicity.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although our findings suggest that eltrombopag or other thrombopoietin receptor agonists may provide an alternative approach to the treatment of this disease in children, specific clinical trials need to be conducted to confirm this hypothesis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rubio-San-Simón A, Rodríguez IL, Gómez FV, Vivanco Martínez JL, Alonso VP. Eficacia y seguridad en el uso del eltrombopag en un caso de aplasia medular adquirida grave. An Pediatr (Barc). 2019;90:246–247.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2927 "Ancho" => 2337 "Tamanyo" => 298993 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Haemoglobin levels and peripheral blood neutrophil counts from initiation of eltrombopag to present. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 27 | 31 | 58 |
| 2024 September | 59 | 25 | 84 |
| 2024 August | 52 | 51 | 103 |
| 2024 July | 39 | 34 | 73 |
| 2024 June | 42 | 23 | 65 |
| 2024 May | 39 | 31 | 70 |
| 2024 April | 60 | 35 | 95 |
| 2024 March | 45 | 19 | 64 |
| 2024 February | 37 | 29 | 66 |
| 2024 January | 33 | 17 | 50 |
| 2023 December | 32 | 32 | 64 |
| 2023 November | 32 | 37 | 69 |
| 2023 October | 24 | 32 | 56 |
| 2023 September | 25 | 30 | 55 |
| 2023 August | 33 | 15 | 48 |
| 2023 July | 39 | 24 | 63 |
| 2023 June | 24 | 44 | 68 |
| 2023 May | 29 | 18 | 47 |
| 2023 April | 29 | 14 | 43 |
| 2023 March | 38 | 19 | 57 |
| 2023 February | 49 | 19 | 68 |
| 2023 January | 26 | 14 | 40 |
| 2022 December | 49 | 17 | 66 |
| 2022 November | 60 | 25 | 85 |
| 2022 October | 58 | 58 | 116 |
| 2022 September | 32 | 20 | 52 |
| 2022 August | 49 | 55 | 104 |
| 2022 July | 42 | 42 | 84 |
| 2022 June | 34 | 35 | 69 |
| 2022 May | 44 | 31 | 75 |
| 2022 April | 38 | 26 | 64 |
| 2022 March | 57 | 49 | 106 |
| 2022 February | 43 | 25 | 68 |
| 2022 January | 49 | 26 | 75 |
| 2021 December | 45 | 44 | 89 |
| 2021 November | 46 | 38 | 84 |
| 2021 October | 61 | 62 | 123 |
| 2021 September | 36 | 28 | 64 |
| 2021 August | 34 | 39 | 73 |
| 2021 July | 32 | 25 | 57 |
| 2021 June | 35 | 34 | 69 |
| 2021 May | 33 | 35 | 68 |
| 2021 April | 130 | 63 | 193 |
| 2021 March | 93 | 27 | 120 |
| 2021 February | 52 | 24 | 76 |
| 2021 January | 52 | 20 | 72 |
| 2020 December | 46 | 17 | 63 |
| 2020 November | 59 | 13 | 72 |
| 2020 October | 58 | 18 | 76 |
| 2020 September | 62 | 15 | 77 |
| 2020 August | 38 | 6 | 44 |
| 2020 July | 41 | 17 | 58 |
| 2020 June | 37 | 9 | 46 |
| 2020 May | 38 | 27 | 65 |
| 2020 April | 22 | 16 | 38 |
| 2020 March | 37 | 7 | 44 |
| 2020 February | 75 | 14 | 89 |
| 2020 January | 55 | 22 | 77 |
| 2019 December | 38 | 17 | 55 |
| 2019 November | 36 | 14 | 50 |
| 2019 October | 19 | 9 | 28 |
| 2019 September | 32 | 7 | 39 |
| 2019 August | 17 | 15 | 32 |
| 2019 July | 21 | 21 | 42 |
| 2019 June | 27 | 20 | 47 |
| 2019 May | 34 | 14 | 48 |
| 2019 April | 47 | 37 | 84 |
| 2019 March | 8 | 7 | 15 |
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