Sun Wei, Sun Yuqian, Mo Xiaodong, Ma Rui, He Yun, Zhang Yuanyuan, Chen Yuhong, Wang Fengrong, Chen Huan, Chen Yao, Yan Chenhua, Han Wei, Xu Lanping, Wang Yu, Zhang Xiaohui, Liu Kaiyan, Huang Xiaojun
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
J Transl Int Med. 2025 May 8;13(2):128-137. doi: 10.1515/jtim-2025-0018. eCollection 2025 Apr.
Haploidentical stem cell transplantation (haplo-HSCT) has demonstrated promising results in patients without severe comorbidities. There is also an increasing need for haplo-HSCT in patients with severe comorbidities. However, the high risk of treatment-related mortality (TRM) hindered its extensive application. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-HSCT in patients with severe comorbidities.
This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia, myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML); (2) patients with no HLA-matched sibling donor or matched unrelated donor available but with a haplo-HSCT donor; (3) patients with hematopoietic cell transplantation comorbidity index (HCT-CI) scores ≥3. The primary endpoint was 2-year TRM.
From June 2018 to November 2022, a total of 72 patients were enrolled. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) at day 100 was 20.8%. The cumulative incidences of cytomegalovirus (CMV) viremia and Epstein‒Barr (EB) viremia at day 100 were 72.2% and 31.9%, respectively. The cumulative incidence of 2-year TRM was 25.1%. The cumulative incidence of 2-year relapse was 8.6%. The probabilities of 2-year overall survival and leukemia-free survival were 71.9% and 65.6%, respectively.
This study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for patients with severe comorbidities. The study was registered as a clinical trial (NCT03412409).
单倍体相合干细胞移植(haplo-HSCT)已在无严重合并症的患者中显示出有前景的结果。对于有严重合并症的患者,对单倍体相合干细胞移植的需求也日益增加。然而,治疗相关死亡率(TRM)的高风险阻碍了其广泛应用。我们旨在研究一种新型预处理方案(Bu/Flu/Cy/ATG),随后对有严重合并症的患者进行单倍体相合干细胞移植。
这项前瞻性单臂临床试验在中国北京大学血液病研究所进行。符合以下条件的患者被纳入研究:(1)诊断为急性白血病、骨髓增生异常综合征(MDS)或慢性粒单核细胞白血病(CMML);(2)没有HLA匹配的同胞供体或匹配的无关供体,但有单倍体相合干细胞移植供体;(3)造血细胞移植合并症指数(HCT-CI)评分≥3。主要终点是2年TRM。
2018年6月至2022年11月,共纳入72例患者。所有患者均实现中性粒细胞植入。100天时II-IV级急性移植物抗宿主病(aGVHD)的累积发生率为20.8%。100天时巨细胞病毒(CMV)血症和EB病毒血症的累积发生率分别为72.2%和31.9%。2年TRM的累积发生率为25.1%。2年复发的累积发生率为8.6%。2年总生存率和无白血病生存率分别为71.9%和65.6%。
本研究表明,一种新型预处理方案联合单倍体相合干细胞移植可能是有严重合并症患者的一种有前景的选择。该研究已注册为一项临床试验(NCT03412409)。