Efficacy and Safety of Hetrombopag Versus Thrombopoietin in Promoting Platelet Engraftment After Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Multicenter, Randomized Controlled Clinical Trial

Abstract

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is pivotal for hematological malignancies but faces challenges in delayed platelet engraftment, poor graft function (PGF), and bleeding risks. Hetrombopag, a thrombopoietin receptor agonist, was evaluated to enhance platelet recovery posttransplant. Patients undergoing allo‐HSCT were randomized on Day 3 Post‐Infusion into low‐dose (2.5 mg/day), high‐dose (5 mg/day) hetrombopag groups, or a control group receiving thrombopoietin (300 U/kg/day). Endpoints included platelet/neutrophil engraftment time, PGF incidence, transfusion needs, and safety. Among 212 analyzed patients, platelet engraftment was faster in hetrombopag groups (median 13 days) versus controls (15 days; p = 0.001), with no dose‐dependent difference (p = 0.821). Neutrophil engraftment was also accelerated (13 vs. 15 days; p = 0.002). PGF incidence was lower in hetrombopag groups (5.04%) versus controls (13.7%; p = 0.042). The experimental group required fewer platelet transfusions (p = 0.021), had reduced gastrointestinal bleeding, and lower costs. Secondary platelet recovery failure showed no intergroup differences. Hetrombopag safely accelerates platelet and neutrophil engraftment, reduces PGF risk, and decreases transfusion dependency post‐allo‐HSCT. Low‐dose hetrombopag demonstrated efficacy equivalent to high‐dose, offering a cost‐effective strategy to improve transplant outcomes.Trial Registration: ChiCTR2200057764.