关键词: CD8+ T cells graft haematopoietic stem cell transplantation haploidentical donor myeloablative conditioning regimen

来  源:   DOI:10.1002/cti2.1484   PDF(Pubmed)

Abstract:
UNASSIGNED: This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT).
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要:
本研究调查了基于抗胸腺细胞球蛋白(ATG)的清髓性单倍体相合造血干细胞移植(haplo-HSCT)的外周血移植物的细胞组成。
在2016年1月至2020年2月期间,在基于ATG的清髓性单倍体HSCT的训练队列中对临床特征进行了回顾性评估,并在2020年3月至2021年6月期间的验证队列中进行了确认。
较高剂量的移植物CD8+T细胞(≥0.85×108kg-1)可显著提高总生存率(OS;风险比[HR],1.750;P=0.002)和无病生存率(DFS;HR,1.751;P<0.001)在训练队列中,根据多变量Cox回归分析。较高剂量的单核细胞(MNCs)表现出更好的OS(HR,1.517;P=0.038)和DFS(HR,1.532;P=0.027)。患者年龄较大(>46岁),年龄较大(≥50岁)和较高的精细疾病风险指数(rDRI)也与OS相关.基于移植物CD8+T细胞剂量的移植物CD8+T细胞风险系统,在LASSOCox回归分析后,使用列线图模型构建供者年龄和rDRI.它显示出可接受的歧视,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),与动员前外周血淋巴细胞百分比较高呈正相关(P<0.001)。
外周血来源的移植物中更高的CD8+T细胞剂量可改善基于ATG的清髓性单plo-HSCT患者的生存率。淋巴细胞百分比较高的年轻供体改善了具有中等rDRI风险的患者的生存率。
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