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异体相合造血干细胞输注联合间充质干细胞治疗 ALL 患者。

Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.

机构信息

Air Force Medical Center, PLA, Road Fucheng 30, Beijing, 100142, P.R. China.

Department of Experimental Hematology& Biochemistry, Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P.R. China.

出版信息

Bone Marrow Transplant. 2022 Jul;57(7):1086-1094. doi: 10.1038/s41409-022-01688-5. Epub 2022 Apr 25.

Abstract

Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients.

摘要

尽管单倍体造血干细胞移植(haplo-HSCT)几乎为所有急性淋巴细胞白血病(ALL)患者提供了立即进行移植的机会,但它表现出更高的移植物失败和移植物抗宿主病(GVHD)发生率。间充质干细胞(MSCs)的特征在于其具有促进造血和免疫调节的能力。因此,我们设计了haplo-HSCT 和 MSCs 联合用于 ALL 患者的方案。110 例 ALL 患者接受了单倍体造血干细胞联合异基因 MSCs,56 例未输注 MSC 的 ALL 患者作为对照。与未输注 MSC 的患者相比,输注 MSC 的患者在第 100 天发生≥2 级急性 GVHD(aGVHD)和≥3 级 aGVHD 的累积发生率分别为 40.00%和 9.09%(P=0.79)和 22.79%(P=0.03)。与未输注 MSC 的患者相比,输注 MSC 的患者在第 3 年发生慢性 GVHD(cGVHD)和广泛型 cGVHD 的累积发生率分别为 22.27%和 10.27%(P=0.19)和 22.21%(P=0.04)。输注 MSC 组和未输注 MSC 组在 3 年复发率、非复发死亡率、无白血病生存率和总生存率方面无显著差异。多变量分析表明,MSC 输注可降低广泛型 cGVHD 的风险。我们的数据表明,haplo-HSCT 联合 MSCs 可能为 ALL 患者提供一种有效且安全的治疗方法。

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