Rudakova Tatiana A, Vlasova Julia Yu, Paina Olesya V, Slesarchuk Olga A, Gorodnova Marina A, Schegoleva Tatiana S, Goloshchapov Oleg V, Bykova Tatiana A, Morozova Elena V, Zubarovskaya Lyudmila S, Moiseev Ivan S, Kulagin Alexander D
RM Gorbacheva Research Institute, Pavlov University, Saint Petersburg, Russia.
Front Med (Lausanne). 2025 Mar 27;12:1551066. doi: 10.3389/fmed.2025.1551066. eCollection 2025.
Hematopoietic stem cell transplantation (HSCT) offers a potential cure for various hematologic malignancies and non-malignant disorders but is often accompanied by severe complications, one of the most challenging being transplant-associated thrombotic microangiopathy (TA-TMA). Eculizumab, a complement inhibitor, has emerged as an effective therapeutic option for TA-TMA.
This single-center retrospective study was conducted at Pavlov University, St. Petersburg, to evaluate the efficacy of eculizumab in 14 adult and pediatric patients who developed high-risk TA-TMA following HSCT between 2015 and 2023. Treatment response was assessed by monitoring organ functions, blood counts, transfusion requirements, the presence of schistocytes in peripheral blood, and increased serum lactate dehydrogenase (LDH). The primary endpoint was overall survival at 100 days from eculizumab administration. Secondary endpoints included the cumulative incidence of a 25% decrease in serum lactate dehydrogenase levels and to the limit of the normal range for age from the date of the initiation of eculizumab, the cumulative incidence of a 50% increase in platelet count or stable platelet levels ≥ 20×10/l was 74% (95% CI, 32-92) with median time 21 days (range: 1-104), cumulative incidence of platelet level ≥ 50×10/l, and 1 year from the date of the initiation of eculizumab.
Overall survival at 100 days was 57% (95%CI, 36-90). The cumulative incidence of LDH decreased by 25% was 89% (95% CI, 26-99) with a median time of 11 days (range: 2-27). Cumulative incidence of LDH ≤ 1.5 upper reference limits (URLs) after eculizumab therapy was 73% (95% CI, 34-91) with a median time of 22 days (range: 2-170). The cumulative incidence of a 50% increase in platelet level or stable platelet level ≥ 20×10/l was 74% (95% CI, 32-92) with a median time of 21 days (range: 1-104). The cumulative incidence of platelet level ≥ 50×109/l was 56% (95% CI, 22-80) with a median time of platelet increase of 75 days (range: 5-384). Complete response was documented in 57% of the group.
In summary, eculizumab is a well-tolerated promising therapeutic intervention for TA-TMA, but more studies are needed to establish its timing and dosage regimen in TA-TMA.
造血干细胞移植（HSCT）为各种血液系统恶性肿瘤和非恶性疾病提供了潜在的治愈方法，但常伴有严重并发症，其中最具挑战性的之一是移植相关血栓性微血管病（TA-TMA）。依库珠单抗，一种补体抑制剂，已成为TA-TMA的有效治疗选择。
本单中心回顾性研究在圣彼得堡的巴甫洛夫大学进行，以评估依库珠单抗对2015年至2023年间HSCT后发生高危TA-TMA的14例成人和儿童患者的疗效。通过监测器官功能、血细胞计数、输血需求、外周血中裂体细胞的存在以及血清乳酸脱氢酶（LDH）升高来评估治疗反应。主要终点是从依库珠单抗给药起100天的总生存率。次要终点包括从依库珠单抗开始使用之日起血清乳酸脱氢酶水平降低25%并降至年龄正常范围上限的累积发生率、血小板计数增加50%或血小板水平稳定≥20×10⁹/L的累积发生率，以及从依库珠单抗开始使用之日起1年时血小板水平≥50×10⁹/L的累积发生率。
100天的总生存率为57%（95%CI，36 - 90）。LDH降低25%的累积发生率为89%（95%CI，26 - 99），中位时间为11天（范围：2 - 27）。依库珠单抗治疗后LDH≤1.5倍参考上限（URLs）的累积发生率为73%（95%CI，34 - 91），中位时间为22天（范围：2 - 170）。血小板水平增加50%或血小板水平稳定≥20×10⁹/L的累积发生率为74%（95%CI，32 - 92），中位时间为21天（范围：1 - 104）。血小板水平≥50×10⁹/L的累积发生率为56%（95%CI，22 - 80），血小板增加的中位时间为75天（范围：5 - 384）。该组中有57%记录了完全缓解。
总之，依库珠单抗是一种耐受性良好的、对TA-TMA有前景的治疗干预措施，但需要更多研究来确定其在TA-TMA中的使用时机和剂量方案。
