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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作者单位:南京医科大学第一附属医院

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Effect of graft composition on the prognosis of allogeneic hematopoietic stem cell transplantation
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Department of Hematology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital

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    摘要:

    目的:探讨移植物中单个核细胞(mononuclear cells,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(regulatory T cell,Treg)细胞剂量及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+细胞(≥6.90×106/kg)(P=0.000)、CD3+T细胞(≥6.24×108/kg)(P=0.042)和CD8+T细胞(≥1.05×108/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/kg)、高剂量CD3+T细胞和CD4+/CD8+T细胞比值<3.57组有更好的OS,高剂量MNC组有更好的PFS(P=0.061)。多因素分析显示,CD4+/CD8+T细胞比值< 3.57组有更好的OS(HR=0.288,95%CI:0.084-0.988,P=0.048)。1年和3年累积复发率(cumulative incidence of relapse,CIR)分别为18.2%和26.8%,高剂量MNC和CD8+T细胞组的患者有更低的CIR。结论:移植物细胞组分对异基因造血干细胞移植预后有着重要影响,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CIR。

    Abstract:

    Objective: To investigate the impact of the graft content of 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=0.000), 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 recurrence rates (CIR) were 18.2% and 26.8%, respectively. Patients in the higher MNC and CD8+ T-cell groups had lower CIR. Conclusion: High CD34+ cell, CD3+ T cells and CD8+ T cells were associated with faster reconstruction of neutrophils and high CD34+ cells promoted platelet engraftment. Patients with CD4+/CD8+ T cells <3.57 had better OS.

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  • 收稿日期:2022-10-08
  • 最后修改日期:2023-04-17
  • 录用日期:2023-07-09
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