Eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after allogeneic haematopoietic stem cell transplantation

Br J Clin Pharmacol. 2021 Apr;87(4):2023-2031. doi: 10.1111/bcp.14607. Epub 2020 Dec 7.

Abstract

Aims: The purpose of this study is to examine the safety and efficacy of eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT).

Methods: Forty-three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed.

Result: Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty-five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P = .035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5-0.9, P = .022), platelet engraftment time (HR = 1.0, 95%CI 1.0-1.0, P = .012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5-43.3, P = .016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver-operating characteristic curve, the optimal cut-off value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver-operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability.

Conclusion: Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d.

Keywords: children; eltrombopag; haematopoietic stem cell transplantation; thrombocytopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / therapeutic use
  • Child
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Hydrazines
  • Pyrazoles
  • Retrospective Studies
  • Thrombocytopenia* / drug therapy
  • Thrombocytopenia* / etiology

Substances

  • Benzoates
  • Hydrazines
  • Pyrazoles
  • eltrombopag