CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Rectal Colonization with Multidrug-Resistant Organisms and Subsequent Bloodstream Infections in Hematological Patients Undergoing Cellular Therapies.
Rectal Colonization with Multidrug-Resistant Organisms and Subsequent Bloodstream Infections in Hematological Patients Undergoing Cellular Therapies.
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细菌感染,尤其是血流感染(BSIs),会影响接受细胞治疗的血液系统恶性肿瘤患者的总生存期。直肠被不同类型多重耐药菌(MDRO)定植与随后发生 BSIs 之间的相互作用尚未完全明确。
我们旨在描述 MDRO 定植的自然病程及其危险因素,以及在抗菌药物耐药环境下其对照细胞治疗患者随后发生 BSIs 的影响。回顾性、单中心队列研究,连续纳入2021年至2024年间在 Attikon 大学医院(希腊)接受异基因或自体造血细胞移植(HCT)或CAR-T 细胞治疗的成年血液系统恶性肿瘤患者,这些患者均有1次可用的针对碳青霉烯耐药革兰阴性杆菌(CR-GNB)和耐万古霉素屎肠球菌(VRE)的直肠筛查检测结果。采用单因素和多因素 Cox 回归识别 CR-GNB 和 VRE 定植的预测因素。
我们还研究了直肠定植与随后 BSIs 之间的一致性。共纳入182例患者(男性:64%,平均年龄:50.2 13 yr,急性髓系白血病/骨髓增生异常综合征诊断:55%,复发/难治性疾病:58%,异基因 HCT:85%)。住院和中性粒细胞减少的中位持续时间分别为 35 d 和 15 d。基线时,95%的患者 CR-GNB 和 VRE 直肠筛查均为阴性,其中在随访期间分别有 8.4% 和 23% 发生 CR-GNB 和 VRE 定植。既往同一病原体定植是随后 CR-GNB(HR: 13.0, 95% CI: 2.83 至 59.3)和 VRE(HR: 4.83, 95% CI: 2.28 至 10.2) 定植。
79 例患者发生 1 次 BSI(革兰阳性菌:60%,革兰阴性菌:38%),其中 16 例定植患者中出现 3 例一致的 CR-GNB BSI(18.7%),153 例非定植患者中出现 2 例 CR-GNB BSI(1.3%)。关于 VRE,我们在 45 例定植患者中确认了 2 例一致的 BSI(4.4%)。尽管 MDRO 患病率高,我们观察到接受细胞治疗的中性粒细胞减少患者中 CR-GNB 定植率较低,5 例患者中有 1 例发生了一致的 CR-GNB BSI。VRE 定植更为常见,但很少导致一致的 BSI。这些发现凸显了感染控制策略的重要性,并支持在该脆弱人群发热性中性粒细胞减少的经验性抗菌治疗中采用降阶梯策略。
Bacterial infections, especially bloodstream infections (BSIs), compromise the overall survival of patients with hematological malignancies undergoing cellular therapies. The interplay between rectal colonization by different types of multidrug-resistant organisms (MDRO) and subsequent BSIs is not fully determined.
We aimed to describe the natural history and risk factors for colonization by MDRO, as well as its impact on subsequent BSIs in patients treated with cellular therapies in an environment of antimicrobial resistance.
Retrospective, single-center cohort study of consecutive adult hematological malignancies patients treated with allogeneic or autologous hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell therapy between 2021 and 2024 in Attikon University Hospital (Greece), with 1 available rectal screening test for carbapenem-resistant gram-negative bacilli (CR-GNB) and vancomycin-resistant Enterococcus faecium (VRE). Univariate and multivariate Cox regression were implemented for identifying predictors of CR-GNB and VRE colonization.
We also studied the concordance between rectal colonization and subsequent BSIs. One hundred eighty-two patients were included (male: 64%, mean age: 50. 2 13 yr, acute myeloid leukemia/myelodysplastic syndrome diagnosis: 55%, relapsing/refractory disease: 58%, allogeneic HCT: 85%). Median duration of hospitalization and neutropenia was 35 and 15 d, respectively. At baseline, 95% of patients were negative on rectal screening for both CR-GNB and VRE, and of those, 8. 4% and 23% were colonized with CR-GNB and VRE during follow-up, respectively. Prior colonization with the same pathogen was independently associated with subsequent CR-GNB (HR: 13.
0, 95% CI: 2. 83 to 59. 3) and VRE (HR: 4. 83, 95% CI: 2. 28 to 10. 2) colonization. Seventy-nine patients had 1 BSIs (gram-positive: 60%, gram-negative: 38%), with three concordant CR-GNB BSIs among 16 colonized patients (18. 7%) and two CR-GNB BSIs among 153 noncolonized patients (1. 3%).
Regarding VRE, we identified two concordant BSIs among 45 colonized patients (4. 4%). Despite the high MDRO prevalence, we observed low rates of CR-GNB colonization in neutropenic patients treated with cellular therapies, with one patient out of five experiencing a concordant CR-GNB BSI. VRE colonization was more frequent, but it rarely resulted in a concordant BSI.
These findings highlight the importance of infection control strategies and support de-escalation approaches in empirical antibacterial treatment of febrile neutropenia in this vulnerable population.
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