Zhou Miao, Li Tongyu, Zhang Ping, Lai Yanli, Sheng Lixia, Ouyang Guifang
Department of Hematology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, Zhejiang, 315000, People's Republic of China.
Ningbo Clinical Research Center for Hematologic Malignancies, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, Zhejiang, 315000, People's Republic of China.
Ann Hematol. 2024 May;103(5):1697-1704. doi: 10.1007/s00277-024-05711-1. Epub 2024 Mar 27.
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) stands as a pivotal treatment for hematologic malignancies, often considered the sole effective treatment option. A frequent complication following allo-HSCT is poor graft function (PGF), with one of its primary manifestations being persistent thrombocytopenia (PT), comprising prolonged isolated thrombocytopenia (PIT) and secondary failure of platelet recovery (SFPR). Conventional treatment methods have had poor efficacy and a high transplantation-associated mortality rate. In recent years, the efficacy of eltrombopag has been reported in the treatment of post-transplantation PT, and additional thrombopoietin receptor agonists (TPO-RA) have been developed. Herombopag is a next-generation TPO-RA which has strong proliferation-promoting effects on human TPO-R-expressing cells (32D-MPL) and hematopoietic progenitor cells in vitro. We reviewed eighteen patients with transplantation-associated thrombocytopenia who received herombopag when eltrombopag was ineffective or poorly tolerated and evaluated its efficacy including effects on survival. Herombopag was administered at a median time of 197 days post-transplantation. Six patients achieved complete response (CR), with a median time to CR of 56 days. Five patients achieved partial response (PR), and the median time to PR was 43 days. Seven patients were considered to have no response (NR). The overall response (OR) rate was 61.1%, and the cumulative incidence (CI) of OR was 90.2%. No patients developed herombopag-associated grade 3-4 toxicity. The median follow-up period was 6.5 months. Twelve patients survived and six patients died, with an overall survival rate of 66.7%. This is the first study to demonstrate the efficacy and safety of herombopag in transplantation-associated thrombocytopenia after failing eltrombopag, introducing a new approach in the treatment of PT following allo-HSCT.
异基因造血干细胞移植(Allo-HSCT)是血液系统恶性肿瘤的关键治疗方法,常被视为唯一有效的治疗选择。异基因造血干细胞移植后常见的并发症是移植物功能不良(PGF),其主要表现之一是持续性血小板减少(PT),包括持续性孤立性血小板减少(PIT)和血小板恢复继发失败(SFPR)。传统治疗方法疗效不佳且移植相关死亡率高。近年来,已报道艾曲泊帕在治疗移植后血小板减少方面的疗效,并且已开发出其他血小板生成素受体激动剂(TPO-RA)。海曲泊帕是新一代TPO-RA,在体外对表达人TPO-R的细胞(32D-MPL)和造血祖细胞具有强大的促增殖作用。我们回顾了18例移植相关血小板减少患者,这些患者在艾曲泊帕无效或耐受性差时接受了海曲泊帕治疗,并评估了其疗效,包括对生存的影响。海曲泊帕在移植后中位197天给药。6例患者达到完全缓解(CR),达到CR的中位时间为56天。5例患者达到部分缓解(PR),达到PR的中位时间为43天。7例患者被认为无反应(NR)。总缓解(OR)率为61.1%,OR的累积发生率(CI)为90.2%。没有患者出现与海曲泊帕相关的3-4级毒性。中位随访期为6.5个月。12例患者存活,6例患者死亡,总生存率为66.7%。这是第一项证明海曲泊帕在艾曲泊帕治疗失败后的移植相关血小板减少中的疗效和安全性的研究,为异基因造血干细胞移植后血小板减少的治疗引入了一种新方法。