The impact of helper T cell reconstitution on clinical outcomes after HLA-haploidentical allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancy
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摘要: 目的 探讨恶性血液病患者半相合造血干细胞移植后辅助性T细胞重建对临床预后的影响。方法 纳入2020年7月—2022年12月于西安交通大学第一附属医院血液内科接受半相合造血干细胞移植的恶性血液病患者46例，通过流式细胞术检测移植后外周血T细胞亚群，以供者作为健康对照，分析移植后T细胞重建的规律。通过ROC曲线、Kaplan-Meier生存分析、χ2检验等分析辅助性T细胞重建对移植后患者总生存期(OS) 和急性移植物抗宿主病(aGVHD)的影响。结果 移植后辅助性T细胞恢复较慢，移植后12个月仍显著低于对照组，但呈上升趋势。移植后3个月辅助性T细胞计数 < 70/μL组及移植后9个月辅助性T细胞计数 < 95/μL组OS更差。移植后3个月辅助性T细胞计数 < 90/μL组aGVHD的发生率更高。结论 恶性血液病患者半相合造血干细胞移植后辅助性T细胞恢复较慢，移植后辅助性T细胞重建不良预示更差的OS和更高的aGVHD发生率。可通过动态监测辅助性T细胞重建情况筛选潜在预后不良患者。
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关键词:
- 辅助性T细胞 /
- 半相合造血干细胞移植 /
- 临床预后 /
- 急性移植物抗宿主病
Abstract: Objective To explore the impact of helper T cell reconstitution on clinical outcomes in patients with hematologic malignancies after HLA-haploidentical allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Forty-six patients who received HLA-haploidentical allo-HSCT in the Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from July 2020 to December 2022 were analyzed. T lymphocyte subsets were detected by flow cytometry at different time after transplantation. The clinical data of healthy donors were used as controls to analyze the regularity of T cell reconstitution after transplantation. ROC curves, Kaplan-Meier survival analysis and Chi-square tests were used to analyze the effects of helper T cell reconstitution on overall survival(OS) and acute graft versus host disease(aGVHD).Results Helper T cell recovered slowly after transplantation which were significantly lower than those of healthy controls at 12 months after transplantation, but showed an increasing trend. Helper T cell count < 70/μL after 3 months of transplantation and < 95/μL at 9 months after transplantation predicted poor OS. Helper T cell count < 90/μL at 3 months after transplantation predicted a high incidence of aGVHD.Conclusion The reconstruction of helper T cell after allo-HSCT was slow. Poor reconstruction of helper T cell after transplantation predicted worse OS and a higher incidence of aGVHD. Patients with potentially poor prognosis could be screened by monitoring of helper T cell reconstruction. -
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表 1 移植患者临床特征
临床特征 数值 移植时年龄/岁 34.5(25.0，48.3) 男性/例(%) 27(58.7) 疾病类型/例(%) AML 26(56.5) ALL 16(34.8) MDS 4(8.7) 供者类型/例(%) 子女供父母 17(37.0) 父母供子女 16(34.8) 兄弟姐妹供 13(28.3) 随访时间/月 17.3(13.7，20.9) MNC输注量/(×108/kg) 8.61(7.31，10.71) CD34+细胞输注量/(×106/kg) 6.11(5.24，7.97) 中性粒细胞植入时间/d 11(10，12) 血小板植入时间/d 12(11，14) 
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表 2 移植组与对照组T细胞的比较
M(P25，P75) 免疫细胞计数/μL 移植后3个月 移植后6个月 移植后9个月 移植后12个月 对照组 辅助性T细胞 90.62
(53.30，153.66)1)125.74
(86.44，253.86)1)265.43
(148.69，341.91)1)285.64
(175.15，499.95)1)484.92
(334.99，565.49)杀伤性T细胞 368.31
(235.93，645.09)437.69
(308.78，696.73)707.19
(497.77，1 059.15)1)1 000.02
(657.74，1 410.30)1)445.85
(335.99，569.29)与对照组比较，1)P < 0.05。
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表 3 辅助性T细胞与移植后OS及aGVHD的相关性
项目 移植3个月 移植后6个月 移植后9个月 移植后12个月 r P r P r P r P 辅助性T细胞与OS -0.429 0.003 - - -0.321 0.041 - - 辅助性T细胞与aGVHD -0.528 < 0.001 - - - - - -
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