Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Centre for Computational Biology, University of Birmingham, Birmingham, United Kingdom.
Front Immunol. 2024 Jan 3;14:1332777. doi: 10.3389/fimmu.2023.1332777. eCollection 2023.
Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy although graft versus host disease and relapse remain major complications. We measured the serum protein expression of 92 inflammation-related markers from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation and related values to subsequent clinical outcomes. Low levels of 7 proteins at D0 were linked to GvHD whilst high levels of 7 proteins were associated with relapse. The concentration of 38 proteins increased over 14 days and higher inflammatory response at D14 was strongly correlated with patient age. A marked increment in protein concentration during this period associated with GvHD but reduced risk of disease relapse, indicating a link with alloreactive immunity. In contrast, patients who demonstrated low dynamic elevation of inflammatory markers during the first 14 days were at increased risk of subsequent disease relapse. Multivariate time-to-event analysis revealed that high CCL23 at D14 was associative of AGvHD, CXCL10 with reduced rate of relapse, and high PD-L1 with reduced overall survival. This work identifies a dynamic pattern of inflammatory biomarkers in the very early post-transplantation period and reveals early protein markers that may help to guide patient management.
异基因造血干细胞移植广泛应用于血液系统恶性肿瘤的治疗,尽管移植物抗宿主病和复发仍是主要并发症。我们检测了 49 例患者移植后第 0 天(D0)和 154 例患者移植后第 14 天(D14)的 92 种炎症相关标志物的血清蛋白表达,并将相关值与随后的临床结局相关联。D0 时低水平的 7 种蛋白与 GvHD 相关,而高水平的 7 种蛋白与复发相关。38 种蛋白在 14 天内浓度升高,D14 时更高的炎症反应与患者年龄密切相关。在此期间蛋白浓度的明显增加与 GvHD 相关,但降低了疾病复发的风险,表明与同种异体反应性免疫有关。相比之下,在最初的 14 天内炎症标志物动态升高较低的患者复发风险增加。多变量时间事件分析显示,D14 时 CCL23 升高与急性 GvHD 相关,CXCL10 与复发率降低相关,PD-L1 升高与总生存时间降低相关。这项工作确定了移植后早期炎症生物标志物的动态模式,并揭示了早期蛋白标志物,可能有助于指导患者管理。