First-line hetrombopag combined with immunosuppressive therapy for paediatric severe aplastic anaemia: A prospective randomized controlled trial.

Although the thrombopoietin receptor agonist hetrombopag (HPAG) improves response in adults with severe aplastic anaemia (SAA), its efficacy in paediatric patients remains unclear. In this single-centre, prospective trial, 54 children with newly diagnosed SAA were randomized to receive standard immunosuppressive therapy (IST) alone (n = 27) or combined with HPAG (IST+HPAG, n = 27). The primary end-point was complete response (CR) rate (CRR) at 6 months. Baseline characteristics were balanced. At 6 months, the CRRs were comparable (59.3% vs. 62.9%, p = 0.948) and overall response (OR) rates (ORRs) identical (85.2%) between HPAG+IST and IST groups. At 12 months, ORRs remained identical (77.8%) and CRRs were 62.9% vs. 74.1% (p = 0.875). Time to response showed no significant differences. In children older than 9 years, the 3-month CRR was significantly higher with IST+HPAG (44.4% vs. 27.3%, p = 0.049). Eight grade ≥3 adverse events (primarily elevated liver enzymes) occurred in the IST+HPAG group, all manageable without treatment discontinuation. Rates of clonal events were comparable (23.8% vs. 26.3%). Adding HPAG to first-line IST did not significantly improve early or sustained haematological response rates in paediatric SAA. Routine upfront combination therapy is not warranted for most patients.