Panpan Zhu, Luxin Yang, Yibo Wu, Jimin Shi, Xiaoyu Lai, Lizhen Liu, Yishan Ye, Jian Yu, Yanmin Zhao, Xiaolin Yuan, Huarui Fu, Zhen Cai, He Huang, Yi Luo
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Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; <i>P</i> = 0.038) and DFS (HR, 1.532; <i>P</i> = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8<sup>+</sup> T-cell risk system based on graft CD8<sup>+</sup> T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8<sup>+</sup> T-cell dose was negatively correlated with donor age (<i>P</i> < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (<i>P</i> < 0.001).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>A higher CD8<sup>+</sup> T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 1","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1484","citationCount":"0","resultStr":"{\"title\":\"Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation\",\"authors\":\"Panpan Zhu, Luxin Yang, Yibo Wu, Jimin Shi, Xiaoyu Lai, Lizhen Liu, Yishan Ye, Jian Yu, Yanmin Zhao, Xiaolin Yuan, Huarui Fu, Zhen Cai, He Huang, Yi Luo\",\"doi\":\"10.1002/cti2.1484\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>A higher dose of graft CD8<sup>+</sup> T cells (≥ 0.85 × 10<sup>8</sup> kg<sup>−1</sup>) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; <i>P</i> = 0.002) and disease-free survival (DFS; HR, 1.751; <i>P</i> < 0.001) in the training cohort, according to multivariate Cox regression analysis. 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引用次数: 0
摘要
目的 本研究调查了基于抗胸腺细胞球蛋白（ATG）的髓鞘消融性单倍体造血干细胞移植（haplo-HSCT）外周血移植物的细胞组成。 方法 回顾性评估2016年1月至2020年2月期间基于ATG的髓鞘消融单倍体造血干细胞移植培训队列的临床特征，并在2020年3月至2021年6月期间的验证队列中进行确认。 结果 根据多变量 Cox 回归分析，在训练队列中，较高剂量的移植物 CD8+ T 细胞（≥ 0.85 × 108 kg-1）可显著改善总生存期（OS；危险比 [HR]，1.750；P = 0.002）和无病生存期（DFS；HR，1.751；P < 0.001）。单核细胞（MNC）剂量越高，OS（HR，1.517；P = 0.038）和DFS（HR，1.532；P = 0.027）越好。患者年龄较大（46 岁）、供体年龄较大（≥ 50 岁）和疾病风险指数（rDRI）较高也与 OS 有关。经过 LASSO Cox 回归分析后，使用提名图模型构建了基于移植物 CD8+ T 细胞剂量、供体年龄和 rDRI 的移植物 CD8+ T 细胞风险系统。该系统显示了可接受的区分度，C 指数分别为 0.62 和 0.63。移植物 CD8+ T 细胞剂量与供体年龄呈负相关（P < 0.001），与动员前外周血中较高的淋巴细胞百分比呈正相关（P < 0.001）。 结论 外周血移植物中 CD8+ T 细胞剂量越高，基于 ATG 的髓脱性单倍体造血干细胞移植患者的存活率越高。淋巴细胞百分比较高的年轻供者可提高患者的存活率，但 rDRI 风险居中。
Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation
Objective
This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT).
Methods
Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021.
Results
A higher dose of graft CD8+ T cells (≥ 0.85 × 108 kg−1) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8+ T-cell risk system based on graft CD8+ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8+ T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001).
Conclusion
A higher CD8+ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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