Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated By Prolonged Thrombocytopenia: A Comprehensive Review

Background:Given the improved survival rates observed among post- HCT patients, a convergence with the general population's lifespan underscores the urgency of addressing the associated long-term complications. A salient concern in this regard is post-transplant thrombocytopenia, a protracted condition that poses a substantial risk of morbidity for post-HCT patients. Despite the magnitude of this issue, a universally recognized treatment protocol for post-transplant thrombocytopenia has yet to be established. Thrombopoietin receptor (TpoR) agonists, including both first-generation and second-generation agents, have emerged as pivotal interventions due to their demonstrated efficacy in augmenting platelet production. The utilization of these agents is progressively expanding across diverse thrombocytopenic conditions. Consequently, we embarked on an exhaustive literature review to deliver an updated and comprehensive assessment of the use of TpoR agonists. Our aim is to explore the efficacy and safety of these agents specifically in the context of treating prolonged post-HCT thrombocytopenia

methodology: A comprehensive search strategy was employed in the PubMed database, covering the period from 1996 to the first of November 2023, with the aim of thoroughly investigating the utilization of TpoR agonists in addressing thrombocytopenia following HCT. The predefined search strategy incorporated medical subject headings (MeSH) terms such as “Thrombopoietin,” “Hematopoietic Stem Cell Transplantation,” and “Thrombocytopenia.” The articles identified underwent assessment for eligibility by two independent reviewers, considering relevance. Subsequently, the selected articles were retrieved and subjected to full-text assessment by two reviewers independently, adhering to inclusion and exclusion criteria

results:We identified 64 reports on the utility of TpoR agonists, five of them were randomized controlled trials and the rest were retrospective observational studies and case series, with a total number of 1730 patients. Second-generation TpoR agonists appear more convenient than subcutaneous recombinant human thrombopoietin (rhTpo) as they can be orally administered and exhibit similar efficacy in platelet recovery, as indicated by recent trial results. Among these agents, avatrombopag, unlike eltrombopag, does not require any dietary restrictions, which could be more favorable for patients. However, eltrombopag remains the most extensively studied agent

Conclusion: Clinical studies of second-generation TpoR agonists, including romiplostim, eltrombopag, avatrombopag, and herombopag demonstrated promising effectiveness in promoting platelet recovery post-HCT, albeit with variations in response rates. Second-generation TpoR agonists seem to be more convenient than subcutaneous rhTpo as they are orally administered with a reasonable platelet recovery as. shows a simplified flowchart for the suggested use of second-generation TpoR agonists in post-HCT thrombocytopenia. Nevertheless, the overall efficacy and safety of TpoR agonist agents post-HCT necessitate further exploration through larger, well-structured clinical trials to optimize their use and ensure their place in standard clinical practice

No relevant conflicts of interest to declare.