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中华移植杂志(电子版) doi: 10.3877/cma.j.issn.1674-3903.2024.01.000

论著

重型β-地中海贫血患儿异基因造血干细胞移植后淋巴细胞亚群动态分析
李赞1, 许芝彬2, 冯志金1, 张雄1,()   
  1. 1. 525099 茂名市人民医院血液科 南方医科大学附属茂名医院血液科 广东医科大学附属茂名临床医学院
    2. 510120 广州医科大学附属第一医院 广州呼吸健康研究院器官移植科
  • 收稿日期:2023-10-23
  • 通信作者: 张雄
  • 基金资助:
    2022年茂名市科技计划项目(2022128)

Dynamic analysis of lymphocyte subsets in children with severe β-thalassemia after allogeneic hematopoietic stem cell transplantation

Zan Li1, Zhibin Xu2, Zhijin Feng1, Xiong Zhang1,()   

  1. 1. Department of Hematology, Maoming People′s Hospital, Maoming Hospital Affiliated to Southern Medical University, Maoming Clinical College of Medicine, Guangdong Medical University, Maoming 525099, China
    2. Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China
  • Received:2023-10-23
  • Corresponding author: Xiong Zhang
引用本文:

李赞, 许芝彬, 冯志金, 张雄. 重型β-地中海贫血患儿异基因造血干细胞移植后淋巴细胞亚群动态分析[J]. 中华移植杂志(电子版), doi: 10.3877/cma.j.issn.1674-3903.2024.01.000.

Zan Li, Zhibin Xu, Zhijin Feng, Xiong Zhang. Dynamic analysis of lymphocyte subsets in children with severe β-thalassemia after allogeneic hematopoietic stem cell transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), doi: 10.3877/cma.j.issn.1674-3903.2024.01.000.

目的

分析重型β-地中海贫血患儿异基因造血干细胞移植(allo-HSCT)术前和术后各时间节点淋巴细胞亚群重建情况。

方法

选取茂名市人民医院2021年12月至2023年8月收治的22例接受亲缘供者allo-HSCT的重型β-地中海贫血患儿为研究对象,动态监测所有患儿allo-HSCT术前以及术后10、30和60 d淋巴细胞亚群变化情况,包括CD3 T细胞比例、CD3 CD4 T细胞比例、CD3 CD8 T细胞比例、CD19 B细胞比例、CD16 CD56 NK细胞比例和CD4/CD8比值。比较HLA全相合与不全相合以及不同性别患儿各时间节点淋巴细胞亚群变化情况。受者回输供者外周血干细胞当天,同时检测亲缘供者的淋巴细胞亚群情况,分析供者免疫情况与患儿术后aGVHD发生的相关性。计量资料以均值±标准差(±s)表示,采用成组t检验或重复测量方差分析进行比较;计数资料以频数表示,采用Fisher确切概率法进行比较。P<0.05为差异有统计学意义。

结果

22例患儿移植成功率100%,均脱离输血,其中HLA全相合15例,HLA不全相合7例,两组患儿性别构成、年龄以及三系植入时间差异均无统计学意义。患儿术后NK细胞比例和B细胞比例恢复相对较快,NK细胞比例在术后10 d和30 d均超过术前水平(P均<0.05),术后60 d回落至术前水平。B细胞比例在术后30 d短暂回落,术后60 d升至高于术后30 d水平,但仍低于术前水平(P均<0.05)。CD3 T细胞比例和CD8 T细胞比例均在术后10 d出现短暂回落(P均<0.05),术后30 d和60 d恢复至术前水平,但差异均无统计学意义(P均>0.05)。CD4 T细胞比例术后各时间点均低于术前水平,但术后60 d与术前相比差异无统计学意义(P>0.05)。术后各时间点CD4/CD8比值均低于术前水平,但差异均无统计学意义(P均>0.05)。HLA全相合与不全相合患儿以及不同性别患儿术前和术后各时间点淋巴细胞亚群差异均无统计学意义(P均>0.05),发生与未发生aGVHD的患儿亲缘供者的淋巴细胞亚群比例差异无统计学意义(P>0.05)。

结论

重型β-地中海贫血患儿allo-HSCT术后淋巴细胞亚群会产生波动,HLA全相合与不全相合及不同性别患儿术后淋巴细胞亚群变化没有差异;亲缘供者淋巴细胞亚群水平与患儿发生aGVHD无关。

Objective

To analyze the reconstitution of lymphocyte subset at various time points before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe β-thalassemia.

Method

Twenty-two children with severe β-thalassemia who completed allo-HSCT from December 2021 to August 2023 in Maoming People′s Hospital were selected as the study objects. The changesof lymphocyte subsets, including CD3+ T cell ratio, CD3+ CD4+ T cell ratio, CD3+ CD8+ T cell ratio, CD19+ B cell ratio, CD16+ CD56+ NK cell ratio and CD4+ /CD8+ ratio, were dynamically monitored before and 10, 30 and 60 days after allo-HSCT in all children. To compare the changes of lymphocyte subsets at each time point between HLA complete and incomplete match children and children of different genders. On the day of donor peripheral blood stem cell reinfusion, lymphocyte subsets of related donors were also measured to analyze the correlation between donor immunity and the occurrence of postoperative acute graft-versus-host disease (aGVHD) in children. Measurement data were expressed as mean±standard deviation (±s) and compared using group t-test or repeated measures analysis of variance; enumeration data were expressed as frequency and compared using Fisher′s exact test. P<0.05 was considered statistically significant.

Results

The success rate of allo-HSCT was 100% in 22 cases, all of which were separated from blood transfusion, including 15 cases of HLA complete match and 7 cases of HLA incomplete matched. There was no significant difference in gender composition, age and three-lineage implantation time between the two groups. The proportion of NK cells exceeded the preoperative level at 10 d and 30 d after allo-HSCT (P<0.05), and decreased to the preoperative level at 60 d after allo-HSCT (P>0.05). The proportion of CD19+ B cells decreased transiently at 30 d after operation and rose to a higher level than 30 d at 60 d after allo-HSCT, but it was still lower than the preoperative level (P<0.05 for all). The proportion of CD3+ T cells and CD8+ T cells showed a transient decrease at 10 d after allo-HSCT (P<0.05 for all), and recovered to the preoperative level at 30 d and 60 d after allo-HSCT, but the differences were not statistically significant (P>0.05 for all). The proportion of CD4+ T cells was lower than the preoperative level at all time points after allo-HSCT, but there was no significant difference between 60 d after allo-HSCT and preoperative level (P>0.05). The CD4+ /CD8+ ratio at each time point after surgery was lower than the preoperative level, but the differences were not statistically significant (P>0.05). There was no statistically significant difference in the changes of lymphocyte subsets between HLA complete and incomplete match children as well as children of different genders at each time points before and after allo-HSCT (P>0.05). There was no significant association in the proportion of lymphocyte subsets between related donors of children who developed and those who did not develop aGVHD (P>0.05).

Conclusion

Lymphocyte subsets fluctuate after allo-HSCT in children with β-thalassemia major, and there is no difference in lymphocyte subsets between HLA complete and incomplete match and between genders; the level of lymphocyte subsets in related donors is not associated with aGVHD in children.

表1 allo-HSCT治疗的22例重型β地中海贫血患儿基线资料
表2 重型β地中海贫血患儿allo-HSCT术前和术后各时间点淋巴细胞亚群比例(±s)
表3 HLA全相合与不全相合患儿allo-HSCT术前和术后各时间点淋巴细胞亚群比例(±s)
表4 不同性别患儿allo-HSCT术前和术后各时间点淋巴细胞亚群比例(±s)
表5 发生与未发生aGVHD的患儿亲缘供者淋巴细胞亚群比例
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