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年龄相关的免疫细胞动力学影响异基因造血细胞移植后的结果。

Age-related immune cell dynamics influence outcomes after allogeneic haematopoietic cell transplantation.

机构信息

Onco-Haematology Paediatric Department, Children's Hospital, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.

Haematology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.

出版信息

Br J Haematol. 2023 Jul;202(1):122-134. doi: 10.1111/bjh.18822. Epub 2023 Apr 24.

Abstract

An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post-transplant immune recovery have been largely investigated across multiple cohorts issuing heterogeneous results. Differences in outcomes in adult and paediatric populations suggest an age-related contribution to post-transplant immune reconstitution; however, it is unclear how recipient and donor age may affect the dynamics of single immune cells. Here, we retrospectively collected and analysed immunological data of 174 patients (58 children and 116 adults) consecutively transplanted for haematological disorders in our centre. We show that trajectories of specific immune cells were strictly dependent on recipient age and pretransplant virus exposure, with the strongest effect seen on T CD4+ and B-cell counterparts, while donor age and transplant platforms had a minimal impact. This mirrored different kinetics of immune reconstitution in adult and paediatric patients, with major divergences in immune cell composition in late post-transplant phases, featuring better survival, relapse-free survival and cumulative incidence of pathogen-specific infections in younger patients. Altogether, these findings underpin the importance of recipient age on post-transplant immune cell recovery and define the basic dynamics of the immune reconstitution in paediatric and adult populations as a benchmark for future studies.

摘要

有效的免疫重建是异基因造血细胞移植(HCT)治疗血液系统疾病成功的基础。影响移植后免疫恢复的因素已在多个队列中进行了广泛研究,但结果存在差异。成人和儿科患者的结果差异表明,年龄是影响移植后免疫重建的一个因素;然而,尚不清楚受者和供者的年龄如何影响单个免疫细胞的动态变化。在这里,我们回顾性地收集和分析了 174 例(58 例儿童和 116 例成人)连续在我们中心接受血液系统疾病 HCT 治疗的患者的免疫数据。我们发现,特定免疫细胞的轨迹严格依赖于受者年龄和移植前病毒暴露,在 T 细胞 CD4+和 B 细胞中观察到最强的影响,而供者年龄和移植平台的影响最小。这反映了成人和儿科患者免疫重建的不同动力学,在移植后晚期,免疫细胞组成存在较大差异,年轻患者的生存、无复发生存和病原体特异性感染的累积发生率更好。总之,这些发现强调了受者年龄对移植后免疫细胞恢复的重要性,并定义了儿科和成人人群免疫重建的基本动力学,为未来的研究提供了基准。

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