Huang Jingtao, Pan Zengkai, Wang Luxiang, Zhang Zilu, Huang Jiayu, Jiang Chuanhe, Cai Gang, Yin Tong
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Clin Exp Med. 2024 Jan 27;24(1):22. doi: 10.1007/s10238-023-01270-3.
The quality of immune reconstitution (IR) is crucial for the outcome of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is closely connected with infection, relapse and graft-versus-host disease (GvHD) which are the most important causes for transplantation failure. However, the IR pattern in the early stage after allo-HSCT, particularly haploidentical (HID) HSCT, remains unclear. In this retrospective study, we examined the T cell reconstitution of patients within the initial 30 days (n = 173) and 100 days (n = 122) after allo-HSCT with myeloablative condition (MAC), of which > 70% were HID HSCT, to assess the influence of IR on the transplant outcomes. By comparing 78 patients with good IR (GIR) to 44 patients with poor IR (PIR), we observed that GIR was associated with lower risk for Epstein-Barr virus (EBV) reactivation and cytomegalovirus (CMV) reactivation, but had no significant impacts on the survival outcomes (i.e., overall survival, event-free survival) and cumulative incidences of GvHD. Importantly, we found lymphocyte reconstitution pattern at day 30 after allo-HSCT would be a surrogate for IR evaluated at day 100. In the Cox proportional hazard model, early reconstitution of CD4, CD4CD25, CD4CD45RO, CD4CD25CD27, and CD8 T cells at day 30 was reversely correlated with risk of EBV reactivation. Finally, we constructed a predictive model for EBV reactivation with CD8 and CD4CD45RO T cell proportions of the training cohort (n = 102), which was validated with a validation cohort (n = 37). In summary, our study found that the quality of IR at day 30 had a predictive value for the risk of EBV reactivation, and might provide guidance for close monitoring for EBV reactivation.
免疫重建（IR）的质量对于接受异基因造血干细胞移植（allo-HSCT）患者的预后至关重要，并且与感染、复发及移植物抗宿主病（GvHD）密切相关，而这些是导致移植失败的最重要原因。然而，allo-HSCT后早期，尤其是单倍体相合（HID）HSCT后的IR模式仍不清楚。在这项回顾性研究中，我们检查了接受清髓预处理（MAC）的allo-HSCT后最初30天内（n = 173）和100天内（n = 122）患者的T细胞重建情况，其中超过70%为HID HSCT，以评估IR对移植结局的影响。通过比较78例免疫重建良好（GIR）患者和44例免疫重建不良（PIR）患者，我们观察到GIR与较低的EB病毒（EBV）激活和巨细胞病毒（CMV）激活风险相关，但对生存结局（即总生存、无事件生存）和GvHD的累积发生率无显著影响。重要的是，我们发现allo-HSCT后第30天的淋巴细胞重建模式可作为第100天评估的IR的替代指标。在Cox比例风险模型中，第30天CD4、CD4CD25、CD4CD45RO、CD4CD25CD27和CD8 T细胞的早期重建与EBV激活风险呈负相关。最后，我们构建了一个基于训练队列（n = 102）中CD8和CD4CD45RO T细胞比例的EBV激活预测模型，并用验证队列（n = 37）进行了验证。总之，我们的研究发现第30天的IR质量对EBV激活风险具有预测价值，并可能为密切监测EBV激活提供指导。
