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:Early de-escalation of antibiotic therapy in hospitalized cellular therapy adult patients with febrile neutropenia.
Early de-escalation of antibiotic therapy in hospitalized cellular therapy adult patients with febrile neutropenia.
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发热性中性粒细胞减少症(FN)是造血细胞移植(HCT)和嵌合抗原受体(CAR)T 细胞治疗患者常见的肿瘤急症,需要立即开始广谱抗生素治疗。关于中性粒细胞减少患者抗生素降阶梯(DE)的数据有限,指南建议也不一致。
本研究实施了一项广谱抗生素降阶梯临床方案:患者退热满 72 小时且无临床感染证据时,可进行抗生素 DE。主要终点是实施 DE 方案前后两组抗生素治疗天数的差异。次要终点包括索引住院期间后续菌血症发生率、30 天死亡率和住院时间。通过回顾性病历审查,比较按照抗生素降阶梯方案接受异基因 HCT、自体 HCT 或 CAR-T 细胞治疗的患者(方案实施后组)与未按方案治疗者(方案实施前组)的结局。方案实施前组于 2018 年 2 月至 9 月接受 HCT/CAR-T 细胞治疗(n=64),实施后组于 2019 年 2 月至 9 月接受治疗(n=67)。实施后组抗生素中位疗程显著短于实施前组:6 天(范围 3–60 天)对 8 天(范围 3–31 天)(p=0.034)。各项次要终点均无差异。
我们认为,对于接受至少 3 天广谱抗生素、已退热且无明确感染证据的中性粒细胞减少 HCT 或 CAR-T 细胞治疗患者,抗生素 DE 是安全有效的做法。采用该方案可显著减少抗生素使用天数,且不损害患者结局。
Febrile neutropenia (FN) is an oncologic emergency frequently encountered in hematopoietic cell transplant (HCT) and chimeric antigen receptor (CAR) T-cell therapy patients, which requires immediate initiation of broad-spectrum antibiotics. Data regarding antibiotic de-escalation (DE) in neutropenic patients are limited, and guideline recommendations vary. A clinical protocol for antibiotic DE of broad-spectrum agents was implemented if patients were afebrile after 72 hours and had no clinical evidence of infection. The primary endpoint was the difference in the number of antibiotic therapy days between the pre-and post-DE protocol implementation group.
Secondary endpoints included rates of subsequent bacteremia during index hospitalization, 30-day mortality, and hospital length of stay. Retrospective chart reviews were conducted to assess outcomes for patients who received allogeneic HCT, autologous HCT, or CAR T-cell therapy under the antibiotic de-escalation protocol (post-DE) compared to those who did not (pre-DE).
The pre-DE group underwent HCT/CAR T-cell from February 2018 through September 2018 (n=64), and the post-DE group from February 2019 through September 2019 (n=67). The median duration of antibiotics was significantly lower in the post-DE group (6 days; range 3-60 days) compared to the pre-DE group (8 days; range 3-31 days) (p=0. 034). There were no differences in any secondary endpoints.
We conclude that antibiotic DE in neutropenic HCT or CAR T-cell therapy patients treated with broad-spectrum antibiotics for at least three days who are afebrile and without documented infection appears to be a safe and effective practice. Adopting it significantly reduces the number of days of antibiotics without compromising patient outcomes.
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