细胞因子释放综合征严重程度及其与 T 细胞富含haploidentical 相关供体移植后感染的关系。
Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation.
机构信息
Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin; BMT & Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
BMT & Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Center of International Blood and Marrow Transplant Research, Milwaukee, Wisconsin; Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
出版信息
Biol Blood Marrow Transplant. 2020 Sep;26(9):1670-1678. doi: 10.1016/j.bbmt.2020.06.006. Epub 2020 Jun 17.
An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity. In our study cohort, which was stratified into 3 groups by severity of CRS, 80% of the patients developed infections within 180 days of HCT. Significantly higher proportions of patients with CRS grade 2 (89%) and grade ≥3 (90%) than patients with CRS grade 0-1 (68%) had at least 1 infection in the first 100 days (P = .04). Bloodstream infections (BSIs) were seen more frequently in patients with CRS grade 2 and grade ≥3 in the first 6 months. Multivariable analysis for time to infection showed that CRS grade ≥3 was independently associated with an elevated risk of any infection compared with CRS grade 0-1 (hazard ratio [HR], 3.05; P = .007). CRS grade ≥3 was also associated with a higher hazard of viral (HR, 3.42; P = .04) and bacterial infections (HR, 2.83; P = .03) compared with CRS grade 0-1. After adjusting for time to neutrophil engraftment as a time-dependent covariate, CRS grade ≥3 still had a significant effect on viral infections (HR, 2.49; P = .03), but not on bacterial infections (HR, 1.32; P = .57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day +100 was higher in patients with severe CRS. Severe CRS developing after post-transplantation cyclophosphamide-based haploHCT is independently associated with viral infections and an increased risk of bacterial infections, likely through delayed neutrophil engraftment.
在 T 细胞完全同种异体造血细胞移植（haploHCT）后，已描述了感染风险增加。haploHCT 后细胞因子释放综合征（CRS）是一种已知现象，但 CRS 严重程度对感染风险的影响仍未得到探索。我们回顾性评估了 2012 年至 2018 年间 78 例连续成年 haploHCT 受者的 CRS 发展情况（根据 Lee 等人的标准进行分级），并检查了 CRS 严重程度与感染相关的发病率和死亡率。在我们的研究队列中，根据 CRS 的严重程度分为 3 组，80%的患者在 HCT 后 180 天内发生感染。CRS 分级 2 级（89%）和分级≥3 级（90%）的患者比 CRS 分级 0-1 级（68%）的患者在第 100 天内至少有 1 次感染的比例显著更高（P=0.04）。在第 6 个月内，CRS 分级 2 级和分级≥3 级的患者中更频繁地出现血流感染（BSI）。多变量分析显示，与 CRS 分级 0-1 级相比，CRS 分级≥3 级与任何感染的风险增加独立相关（危险比[HR]，3.05；P=0.007）。与 CRS 分级 0-1 级相比，CRS 分级≥3 级也与病毒（HR，3.42；P=0.04）和细菌（HR，2.83；P=0.03）感染的风险增加相关。在调整中性粒细胞植入作为时间依赖协变量后，CRS 分级≥3 级对病毒感染仍有显著影响（HR，2.49；P=0.03），但对细菌感染没有影响（HR，1.32；P=0.57）。CRS 分级也是感染密度（整体、细菌和病毒）的重要预测因素。在严重 CRS 患者中，第 100 天感染相关死亡率更高。移植后环磷酰胺为基础的 haploHCT 后发生的严重 CRS 与病毒感染和细菌感染风险增加独立相关，这可能是通过延迟中性粒细胞植入引起的。
Zotero 插件