Luo Fenglian, Luo Zhiming, Luo Yun, Zeng Hanqing, Chen Ying, Cao Chun
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Transplant Cell Ther. 2025 Jun 28. doi: 10.1016/j.jtct.2025.06.023.
Thrombocytopenia remains a significant clinical challenge following peripheral blood stem cell transplantation (PBSCT), with delayed platelet engraftment (DPE) associated with increased morbidity and mortality. While current strategies including platelet transfusions and recombinant human thrombopoietin (rhTPO) are widely used, their clinical utility is constrained by suboptimal efficacy, high costs, and administration challenges. Herombopag, a novel second-generation thrombopoietin receptor agonist (TPO-RA), presents potential advantages due to its oral bioavailability and unique mechanism of action. This retrospective study aimed to comprehensively compare herombopag with rhTPO in terms of hematopoietic recovery, safety profile, and economic impact in both autologous (auto-) and allogeneic (allo-) PBSCT settings.
We conducted a retrospective cohort analysis of 106 consecutive PBSCT patients (56 auto-PBSCT, 50 allo-PBSCT) treated between January 2022 and October 2024. Patients were stratified into two intervention groups: oral herombopag (5 mg/day) versus subcutaneous rhTPO (15,000 U/day), initiated when platelet counts dropped below 30 × 10⁹/L. Primary endpoints included time to neutrophil and platelet engraftment, while secondary endpoints encompassed bleeding events, transfusion requirements, infectious complications (CMV, EBV, BKV), GVHD incidence, drug-related toxicities, and overall treatment costs. Rigorous statistical analyses were performed using SPSS v26.0, employing appropriate parametric and nonparametric tests with statistical significance set at P < .05.
Engraftment Kinetics: In auto-PBSCT, comparable results were observed between groups for both neutrophil (herombopag: 12.25 ± 1.30 days versus rhTPO: 12.43 ± 1.35 days; P = .615) and platelet engraftment (13.32 ± 1.31 versus 13.61 ± 1.23 days; P = .403). Allo-PBSCT patients receiving herombopag demonstrated significantly faster hematopoietic recovery: neutrophil engraftment (12.76 ± 1.81 versus 13.80 ± 1.71 days; P = .042) and platelet engraftment (15.76 ± 2.59 versus 17.72 ± 2.81 days; P = .013).
Bleeding events were markedly reduced with herombopag in both auto-PBSCT (7.1% versus 42.9%; P = .005) and allo-PBSCT (8.0% versus 40.0%; P = .020) cohorts. Platelet transfusion requirements were significantly lower in herombopag-treated patients (auto-PBSCT: 1.11 ± 1.10 versus 2.04 ± 1.07 units, P = .002; allo-PBSCT: 1.64 ± 1.85 versus 3.56 ± 1.96 units, P = .001).
Comparable rates of viral reactivation (CMV, EBV, BKV), GVHD, and manageable liver function abnormalities were observed between groups. No thrombotic complications or significant survival differences were noted at 2-year follow-up (OS/PFS, P>0.05).
Herombopag demonstrated substantial cost savings, reducing medication expenses by 87% in auto-PBSCT (median 138.13 versus 1041.04 USD; P = .000) and 84% in allo-PBSCT (211.25 versus 1315 USD; P = .000).
Our findings establish herombopag as an effective and cost-saving alternative to rhTPO, particularly in the allo-PBSCT setting where it demonstrated superior engraftment kinetics. The significant reduction in bleeding complications and transfusion requirements, coupled with its convenient oral administration, positions herombopag as an attractive therapeutic option. While the safety profiles were comparable, herombopag's economic advantages and potential immunomodulatory effects warrant further investigation. Study limitations include its retrospective nature and moderate sample size, highlighting the need for prospective randomized controlled trials to validate these observations.
This study provides robust evidence that herombopag is a safe, effective, and economically favorable therapy for post-PBSCT thrombocytopenia. Its demonstrated benefits in accelerating platelet recovery, reducing hemorrhagic complications, and lowering healthcare costs suggest it should be considered as a preferred therapeutic option, especially for allo-PBSCT recipients. These findings have important implications for optimizing supportive care in hematopoietic stem cell transplantation.
血小板减少症仍然是外周血干细胞移植（PBSCT）后的一项重大临床挑战，血小板植入延迟（DPE）与发病率和死亡率增加相关。虽然目前包括血小板输注和重组人血小板生成素（rhTPO）在内的策略被广泛使用，但其临床效用受到疗效欠佳、成本高昂和给药挑战的限制。海曲泊帕，一种新型第二代血小板生成素受体激动剂（TPO-RA），因其口服生物利用度和独特的作用机制而具有潜在优势。这项回顾性研究旨在全面比较海曲泊帕与rhTPO在自体（auto-）和异基因（allo-）PBSCT环境下的造血恢复、安全性和经济影响。
我们对2022年1月至2024年10月期间接受治疗的106例连续PBSCT患者（56例自体PBSCT，50例异基因PBSCT）进行了回顾性队列分析。患者被分为两个干预组：口服海曲泊帕（5mg/天）与皮下注射rhTPO（15,00 U/天），当血小板计数降至30×10⁹/L以下时开始使用。主要终点包括中性粒细胞和血小板植入时间，次要终点包括出血事件、输血需求、感染并发症（CMV、EBV、BKV）、移植物抗宿主病（GVHD）发生率、药物相关毒性和总体治疗成本。使用SPSS v26.0进行了严格的统计分析，采用适当的参数和非参数检验，设定统计学显著性为P < 0.05。
植入动力学：在自体PBSCT中，两组中性粒细胞（海曲泊帕：12.25±1.30天对rhTPO：12.43±1.35天；P = 0.615）和血小板植入（13.32±1.31对13.61±1.23天；P = 0.403）的结果相当。接受海曲泊帕的异基因PBSCT患者表现出明显更快的造血恢复：中性粒细胞植入（12.76±1.81对13.80±1.71天；P = 0.042）和血小板植入（15.76±2.59对17.72±2.81天；P = 0.013）。
在自体PBSCT（7.1%对%42.9；P = 0.005）和异基因PBSCT（8.0%对40.0%；P = 0.020）队列中，海曲泊帕显著减少了出血事件。接受海曲泊帕治疗的患者血小板输血需求显著更低（自体PBSCT：1.11±1.10对2.04±1.07单位，P = 0.00；异基因PBSCT：1.64±1.85对3.56±1.96单位，P = 0.001）。
两组之间观察到病毒重新激活（CMV、EBV、BKV）、GVHD和可控制的肝功能异常发生率相当。在2年随访中未发现血栓并发症或显著的生存差异（总生存期/无进展生存期，P>0.05）。
海曲泊帕显示出大幅成本节约，在自体PBSCT中药物费用降低了87%（中位数138.13对1041.04美元；P = 0.000），在异基因PBSCT中降低了84%（211.25对1315美元；P = 0.000）。
我们的研究结果表明，海曲泊帕是rhTPO的一种有效且节省成本的替代药物，特别是在异基因PBSCT环境中，它显示出更好的植入动力学。出血并发症和输血需求的显著减少，加上其方便的口服给药方式，使海曲泊帕成为一个有吸引力的治疗选择。虽然安全性相当，但海曲泊帕的经济优势和潜在的免疫调节作用值得进一步研究。研究局限性包括其回顾性性质和中等样本量，这突出了需要进行前瞻性随机对照试验来验证这些观察结果。
本研究提供了有力证据，表明海曲泊帕是PBSCT后血小板减少症的一种安全、有效且经济实惠的治疗方法。它在加速血小板恢复、减少出血并发症和降低医疗成本方面的显著益处表明，它应被视为首选治疗选择，特别是对于异基因PBSCT接受者。这些发现对优化造血干细胞移植的支持性护理具有重要意义。
