Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Front Immunol. 2022 Sep 20;13:954716. doi: 10.3389/fimmu.2022.954716. eCollection 2022.
Lymphocyte neogenesis from primary lymphoid organs is essential for a successful reconstitution of immunity after allogeneic hematopoietic stem cell transplantation (HSCT). This single-center retrospective study aimed to evaluate T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) as surrogate markers for T and B cell recovery, as predictors for transplantation-related outcomes in adult acute myeloid leukemia (AML) patients.
Ninety adult patients diagnosed with AML and treated with HSCT between 2010 and 2015 were included in the study. TREC and KREC levels were measured by quantitative PCR at 1, 3, 6, and 12 months after transplantation.
Overall, excision circle levels increased between 3 and 6 months post-HSCT for TREC (p = 0.005) and 1 and 3 months for KREC (p = 0.0007). In a landmark survival analysis at 12 months post-HSCT, TREC levels were associated with superior overall survival (HR: 0.52, 95% CI: 0.34 - 0.81, p = 0.004). The incidence of viral infections within the first 100 days after transplantation was associated with lower TREC levels at 6 months (p = 0.0002). CMV reactivation was likewise associated with lower TREC levels at 6 months (p = 0.02) post-HSCT. KREC levels were not associated with clinical outcomes in statistical analyzes.
Results from the present study indicate that TREC measurement could be considered as part of the post-HSCT monitoring to identify AML patients with inferior survival after transplantation. Further prospective studies are warranted to validate these findings.
从初级淋巴器官生成淋巴细胞对于异基因造血干细胞移植 (HSCT) 后成功重建免疫至关重要。本单中心回顾性研究旨在评估 T 细胞受体切除环 (TREC) 和 κ 缺失重组切除环 (KREC) 作为 T 和 B 细胞恢复的替代标志物,以及作为成人急性髓细胞白血病 (AML) 患者移植相关结局的预测因子。
本研究纳入了 2010 年至 2015 年间接受 HSCT 治疗的 90 例 AML 成年患者。在移植后 1、3、6 和 12 个月通过定量 PCR 测量 TRECs 和 KRECs 水平。
总体而言,TREC 的切除环水平在 HSCT 后 3 至 6 个月(p = 0.005)和 KREC 的 1 至 3 个月(p = 0.0007)之间增加。在 HSCT 后 12 个月的生存里程碑分析中,TREC 水平与总体生存更好相关(HR:0.52,95%CI:0.34-0.81,p = 0.004)。移植后 100 天内病毒感染的发生率与 6 个月时的 TRECs 水平较低相关(p = 0.0002)。CMV 再激活也与 HSCT 后 6 个月时的 TRECs 水平较低相关(p = 0.02)。在统计分析中,KREC 水平与临床结局无关。
本研究结果表明,TREC 测量可被视为 HSCT 监测的一部分,以识别移植后生存较差的 AML 患者。需要进一步的前瞻性研究来验证这些发现。