Justus Julie Lillian Pimentel, Beltrame Miriam P, de Azambuja Ana Paula, Schluga Yara C, Martins Edna A, Rocha Maria Tadeu Lemes, Rodrigues Adriana Mello, Loth Gisele, Lima Alberto Cardoso Martins, Bonfim Carmem
Flow Cytometry Laboratory, Clinics Hospital, Federal University of Paraná, Curitiba, Brazil; Post-Graduation Program in Children and Adolescent Health, Clinics Hospital, Federal University of Parana, Curitiba, Brazil.
Flow Cytometry Laboratory, Clinics Hospital, Federal University of Paraná, Curitiba, Brazil; Post-Graduation Program in Children and Adolescent Health, Clinics Hospital, Federal University of Parana, Curitiba, Brazil.
Cytotherapy. 2024 Sep;26(9):980-987. doi: 10.1016/j.jcyt.2024.04.073. Epub 2024 May 1.
Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3CD31CD45RA cells.
We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT. We analyzed the distribution of peripheral blood subsets of T, B and natural killer lymphocytes and assessed the impact of underlying disease, HCT type, stem cell source, recipient age, conditioning regimen, graft-versus-host disease (GVHD) occurrence and cytomegalovirus (CMV) reactivation on immune recovery.
At day 100, patients under 10 years exhibited higher RTE CD4 and CD8CD31CD45RA counts compared with older patients (5.3 versus 2.2 cells/µL, P = 0.022 and 48 versus 72.8 cells/µL, P = 0.049, respectively). Patients with haploidentical HCT had lower RTE CD4 counts compared with those with unrelated or related donors (2.4 versus 4.4 versus 7.9 cells/µL, P = 0.024). Administration of rabbit anti-thymocyte globulin negatively impacted RTE CD4 production (median, 6.5 versus 2.4 cells/µL, P = 0.007). At day 180, the presence of GVHD had a negative influence on RTE production (11.7 versus 56.8 cells/µL, P < 0.001), particularly higher-grade acute GVHD (without, 56.8 cells/µL, grade 1-2, 28.1 cells/µL, grade 3-4, 6.0 cells/µL, P < 0.001). Patients with CMV reactivation had higher CD8CD31CD45RA compared with those without reactivation (median, 204.6 versus 100.2 cells/µL, P = 0.022). At day 360, no variables significantly affected RTE recovery. Overall survival at 5-year follow-up was 87.7%, with a median of 1170 days (range, 122-3316). Multivariate analysis showed that age >10 years (P = 0.038), negative CMV donor serology (P = 0.0029) and acute GVHD (P = 0.0026) had a negative impact on survival.
This study highlights variations in RTE production based on patient age, donor type and immunosuppression regimen employed.
造血细胞移植（HCT）后胸腺生成的充分重建对于长期免疫重建至关重要，可能影响患者生存率。本研究旨在通过定量近期胸腺迁出细胞（RTE），特别是CD3CD31CD45RA细胞，评估儿科HCT受者的免疫重建情况。
我们对2013年至2020年间接受首次异基因HCT的186例儿科患者进行了回顾性分析，这些患者在移植后的前100天内存活，并在HCT后的三个时间点进行免疫恢复评估：第100天、第180天和第360天。我们分析了T、B和自然杀伤淋巴细胞外周血亚群的分布，并评估了基础疾病、HCT类型、干细胞来源、受者年龄、预处理方案、移植物抗宿主病（GVHD）的发生以及巨细胞病毒（CMV）再激活对免疫恢复的影响。
在第100天，10岁以下患者的RTE CD4和CD8CD31CD45RA计数高于年龄较大的患者（分别为5.3对2.2细胞/微升，P = 0.022；48对72.8细胞/微升，P = 0.049）。与无关或相关供者的患者相比，单倍体相合HCT患者的RTE CD4计数较低（2.4对4.4对7.9细胞/微升，P = 0.024）。给予兔抗胸腺细胞球蛋白对RTE CD4的产生有负面影响（中位数，6.5对2.4细胞/微升，P = 0.007）。在第180天，GVHD的存在对RTE的产生有负面影响（11.7对56.8细胞/微升，P < 0.001），特别是较高等级的急性GVHD（无，56.8细胞/微升；1-2级，28.1细胞/微升；3-4级，6.0细胞/微升，P < 0.001）。与未再激活的患者相比，CMV再激活的患者CD8CD31CD45RA较高（中位数，204.6对100.2细胞/微升，P = 0.022）。在第360天，没有变量显著影响RTE的恢复。5年随访的总生存率为87.7%，中位数为1170天（范围，122 - 3316）。多变量分析显示，年龄>10岁（P = 0.038）、CMV供者血清学阴性（P = 0.0029）和急性GVHD（P = 0.0026）对生存有负面影响。
本研究强调了基于患者年龄、供者类型和所采用的免疫抑制方案，RTE产生存在差异。
