Mikulski Damian, Kościelny Kacper, Dróżdż Izabela, Nowicki Mateusz, Misiewicz Małgorzata, Perdas Ewelina, Strzałka Piotr, Wierzbowska Agnieszka, Fendler Wojciech
Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
Department of Hematooncology, Provincial Multi-Specialized Oncology and Trauma Center, Lodz, Poland.
Infect Chemother. 2024 Sep;56(3):339-350. doi: 10.3947/ic.2024.0021. Epub 2024 Jun 4.
Autologous hematopoietic stem cell transplantation (AHSCT) is currently the backbone of the treatment of multiple myeloma (MM) and relapsed and refractory lymphomas. Notably, infections contribute to over 25% of fatalities among AHSCT recipients within the initial 100 days following the procedure. In this study, we aimed to evaluate three selected miRNAs: hsa-miR-155-5p, hsa-miR-320c, and hsa-miR-361-3p, in identifying AHSCT recipients at high risk of infectious events up to 100 days post-transplantation after discharge.
The study group consisted of 58 patients (43 with MM, 15 with lymphoma) treated with AHSCT. Blood samples were collected from all patients at the same time point: on day +14 after transplantation.
Fifteen patients (25.9%) experienced infectious complications after post-transplant discharge within the initial +100 days post-transplantation. The median time to infection onset was 44 days (interquartile range, 25-78). Four patients required hospitalization due to severe infection. High expression of hsa-miR-361-3p (fold change [FC], 1.79; =0.0139) in the patients experiencing infectious complications and overexpression of hsa-miR-320c (FC, 2.14; <0.0001) in patients requiring hospitalization were observed. In the multivariate model, both lymphoma diagnosis (odds ratio [OR], 6.88; 95% confidence interval [CI], 1.55-30.56; =0.0112) and high expression of hsa-miR-361-3p (OR, 3.00; 95% CI, 1.40-6.41; =0.0047) were independent factors associated with post-discharge infectious complications occurrence. Our model in 10-fold cross-validation preserved its diagnostic potential with an area under the receiver operating characteristic curve of 0.78 (95% CI, 0.64-0.92).
Elevated serum hsa-miR-361-3p emerges as a promising biomarker for identifying patients at risk of infection during the early post-discharge period, potentially offering optimization of the prophylactic use of antimicrobial agents tailored to the specific risk profile of each AHSCT recipient.
自体造血干细胞移植（AHSCT）目前是多发性骨髓瘤（MM）以及复发和难治性淋巴瘤治疗的支柱。值得注意的是，在AHSCT受者术后最初100天内，感染导致超过25%的死亡。在本研究中，我们旨在评估三种选定的微小RNA：hsa-miR-155-5p、hsa-miR-320c和hsa-miR-361-3p，以识别出院后至移植后100天内有感染事件高风险的AHSCT受者。
研究组由58例接受AHSCT治疗的患者组成（43例MM患者，15例淋巴瘤患者）。在同一时间点，即移植后第14天，采集所有患者的血样。
15例患者（25.9%）在移植后最初100天内出院后出现感染并发症。感染开始的中位时间为44天（四分位间距，25 - 78天）。4例患者因严重感染需要住院治疗。观察到发生感染并发症的患者中hsa-miR-361-3p高表达（倍数变化[FC]，1.79；P = 0.0139），需要住院治疗的患者中hsa-miR-320c过表达（FC，2.14；P < 0.0001）。在多变量模型中，淋巴瘤诊断（比值比[OR]，6.88；95%置信区间[CI]，1.55 - 30.56；P = 0.0112）和hsa-miR-361-3p高表达（OR，3.00；95%CI，1.40 - 6.41；P = 0.0047）都是与出院后感染并发症发生相关的独立因素。我们的模型在10倍交叉验证中保留了其诊断潜力，受试者操作特征曲线下面积为0.78（95%CI，0.64 - 0.92）。
血清hsa-miR-361-3p升高成为一种有前景的生物标志物，用于识别出院后早期有感染风险的患者，有可能优化针对每个AHSCT受者特定风险特征的抗菌药物预防性使用。
