移植物细胞组分对异基因造血干细胞移植预后的影响
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R730.54

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国家自然科学基金(81470329,81600096)


Effect of graft composition on the prognosis of allogeneic hematopoietic stem cell transplantation
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    摘要:

    目的:探讨移植物中单个核细胞(mononuclear cell,MNC)、CD34+ 细胞及 T 淋巴细胞亚群剂量对移植后生存的影响。方法:回顾性分析121例行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)的血液系统恶性疾病患者,研究回输移植物中MNC、CD34+ 细胞、CD3+ T细胞、CD4+ T细胞、CD8+ T细胞、调节性T细胞(regulatory T cell, Treg)剂量及CD4+ /CD8+ T细胞比值对移植后造血重建及生存的影响。结果:中性粒细胞成功植入120例,高剂量CD34+ T细胞 (≥6.90×106 个/kg)(P < 0.001)、CD3+ T细胞(≥6.24×108 个/kg)(P=0.042)和CD8+ T细胞(≥1.05×108 个/kg)(P=0.021)与中性粒细胞更快植入相关。血小板成功植入119例,高剂量CD34+ 细胞与血小板更快植入相关(P=0.001)。53例(43.8%)患者发生急性移植物抗宿主病,28例发生慢性移植物抗宿主病。1年和3年总体生存(overall survival,OS)率为83.5%和68.0%,1年和3年无进展生存(progression-free survival,PFS)率为75.0%和64.4%。单因素分析中,高剂量MNC(≥9.79×108 个/kg)、高剂量CD3+ T细胞和CD4+ /CD8+ T细胞比值<3.57患者有更好的OS,高剂量MNC患者有更好的PFS(P=0.061)。多因素分析显示,CD4+ /CD8+ T 细胞比值<3.57患者有更好的OS(HR=0.288,95%CI:0.084~0.988,P=0.048)。1年和3年累积复发率分别为18.2%和26.8%,高剂量MNC和CD8+ T细胞患者有更低的累积复发率。结论:移植物细胞组分对异基因造血干细胞移植预后有重要影响,高剂量 CD34+ 细胞可促进血小板更快植入,回输移植物中CD4+ /CD8+ T细胞比值<3.57的患者有更好的OS和更低的累积复发率。

    Abstract:

    Objective:To investigate the impact of the graft content including mononuclear cells(MNC),CD34+ cells and T-lymphocyte subsets on post-transplant survival. Methods:A retrospective analysis of 121 patients with hematologic malignant diseases undergoing allogeneic hematopoietic stem cell transplantation(allo -HSCT)was performed to investigate the effects of the doses of MNC,CD34 + cells,CD3+ T cells,CD4+ T cells,CD8+ T cells and regulatory T(Treg)cells in the grafts on hematopoietic reconstitution and survival. Results:Neutrophils were successfully engrafted in 120 patients,and patients with high doses of CD34+ cells(≥6.90×106 /kg)(P < 0.001), CD3+ T cells(≥6.24×108 /kg)(P=0.042)and CD8+ T cells(≥1.05×108 /kg)(P=0.021)had more rapid engraftment of neutrophils. Platelets were successfully engrafted in 119 cases,and high dose CD34 + cells were associated with faster platelet reconstruction(P=0.001). Acute graft-versus-host disease(aGVHD)occurred in 53(43.8%)patients and 28 patients had chronic graft-versus-host disease (cGVHD). One and 3-year overall survival(OS)rates were 83.5% and 68.0%,and one and 3-year progression -free survival(PFS) rates were 75.0% and 64.4%. In univariate analysis,the patients with high MNC dose(≥9.79×108 /kg),high CD3 + T cells dose and CD4+ /CD8+ T cells <3.57 had better OS and the high MNC group had better PFS(P=0.061). Multivariate analysis showed that the CD4+ / CD8+ T-cell < 3.57 group had better OS(HR=0.288,95%CI:0.084~0.988,P=0.048). One and 3-year cumulative incidence of relapse(CIR)were 18.2% and 26.8%,respectively. Patients in the higher MNC and CD8 + T -cell groups had lower CIR. Conclusion:Graft components has an important impact on the prognosis of allo-HSCT. High doses of CD34+ cells promote faster platelet implantation, and patients with a CD4+ /CD8+ T-cell ratio < 3.57 in the graft have better OS and lower CIR.

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刘燕平,李芳,王佳雯,钱思轩,吴汉新,陆化,朱雨,沈文怡,洪鸣,陈丽娟,李建勇,缪扣荣,朱晗.移植物细胞组分对异基因造血干细胞移植预后的影响[J].南京医科大学学报(自然科学版),2023,(7):974-980

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  • 收稿日期:2022-10-08
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  • 在线发布日期: 2023-07-16
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