Qian Jiejing, Huang Xianbo, Mei Chen, Ren Yanling, Fan Cuihua, Ouyang Guifang, Wang Shasha, Xu Yu, Zhuang Sujing, Yang Weijuan, Jin Jie, Tong Hongyan
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Hematological disorders, Hangzhou, China; Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological Maligancies, Hangzhou, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, China.
Department of hematology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
Transplant Cell Ther. 2025 Sep 8. doi: 10.1016/j.jtct.2025.09.005.
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) offers curative potential for hematologic malignancies but is often limited by high incidences of graft-versus-host disease (GVHD), delayed engraftment, and transplant-related mortality-especially when donors are aged ≥40 years. Umbilical cord blood (UCB) infusion may mitigate these risks by promoting immune tolerance and hematopoietic recovery. However, the efficacy of this strategy in the context of older donors remains insufficiently studied.
This study aimed to evaluate the efficacy and safety of combining UCB infusion with haplo-HSCT using older (≥40 years) haploidentical donors in patients with hematologic malignancies.
This was a multicenter, prospective, single-arm phase II clinical trial registered in the Chinese Clinical Trial Registry (ChiCTR2200062553). A total of 45 patients diagnosed with myeloid or lymphoid malignancies received haplo-HSCT with donors aged ≥40 years, followed by UCB infusion within 24 hours. The primary endpoint was the cumulative incidence of grade II-IV acute GVHD by day +100. Secondary endpoints included hematopoietic engraftment, overall survival (OS), disease-free survival (DFS), GVHD-free, relapse-free survival (GRFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and adverse events (AEs).
All patients achieved neutrophil engraftment (median: 12 days) and most achieved platelet engraftment (median: 13 days). Grade II-IV and III-IV acute GVHD occurred in 22.29% and 8.89% of patients, respectively. The 2-year CIR and NRM were 11.49% and 2.44%, respectively. The estimated 2-year OS, DFS, and GRFS were 95.39%, 86.24%, and 76.59%, respectively. Infectious complications were manageable, and adverse events were consistent with expectations for this patient population.
Haplo-HSCT combined with UCB infusion is a safe and effective strategy for patients lacking young donors, offering rapid hematopoietic recovery, low GVHD incidence, and favorable survival outcomes. This approach provides a viable option for donor-limited settings and supports broader application of haploidentical transplantation in aging populations.
单倍型造血干细胞移植（haplo-HSCT）为血液系统恶性肿瘤提供了治愈潜力，但常因移植物抗宿主病（GVHD）发生率高、植入延迟和移植相关死亡率而受限，尤其是当供体年龄≥40岁时。输注脐带血（UCB）可能通过促进免疫耐受和造血恢复来减轻这些风险。然而，在老年供体背景下该策略的疗效仍研究不足。
本研究旨在评估在血液系统恶性肿瘤患者中，将UCB输注与使用年龄较大（≥40岁）的单倍型供体进行haplo-HSCT相结合的疗效和安全性。
这是一项在中国临床试验注册中心（ChiCTR2200062553）注册的多中心、前瞻性、单臂II期临床试验。共有45例诊断为髓系或淋巴系恶性肿瘤的患者接受了年龄≥40岁供体的haplo-HSCT，随后在24小时内输注UCB。主要终点是至+100天时II-IV级急性GVHD的累积发生率。次要终点包括造血植入、总生存期（OS）、无病生存期（DFS）、无GVHD无复发生存期（GRFS）、复发累积发生率（CIR）、非复发死亡率（NRM）和不良事件（AE）。
所有患者均实现中性粒细胞植入（中位时间：12天），大多数患者实现血小板植入（中位时间：13天）。II-IV级和III-IV级急性GVHD分别发生在22.29%和8.89%的患者中。2年CIR和NRM分别为11.49%和2.44%。估计2年OS、DFS和GRFS分别为95.39%、86.24%和76.59%。感染性并发症可控，不良事件与该患者群体的预期一致。
haplo-HSCT联合UCB输注对于缺乏年轻供体的患者是一种安全有效的策略，可实现快速造血恢复、低GVHD发生率和良好的生存结果。这种方法为供体受限的情况提供了一个可行的选择，并支持单倍型移植在老年人群中更广泛的应用。
