肿瘤细胞治疗研究
英文原题：Infections in the First 30 Days after Chimeric Antigen Receptor T-Cell Therapy in Patients Not Receiving Fluoroquinolone Prophylaxis.
约 204 例成人（中位年龄 64 岁，IQR：57 至 71）接受了 tisagenlecleucel（50%）和 axicabtagene（50%），此前中位接受过 3 线治疗（四分位距 [IQR]：3 至 4）。
对接受CAR-T 细胞治疗的血液系统恶性肿瘤患者常规预防性使用氟喹诺酮类药物（FQ），可能增加抗菌药物耐药、微生物组紊乱和艰难梭菌感染风险。澳大利亚并非常规使用 FQ 预防。本研究评估未接受 FQ 预防的一组患者在 CAR-T 后早期发热的病因，以了解感染（尤其是血流感染）的发生情况。这项澳大利亚双中心回顾性研究纳入 2019 至 2023 年接受标准治疗 CD19 CAR-T 的成人 DLBCL 患者。主要结局为输注日至第 30 天持续发热的原因（原文发热定义符号/时间条件有缺损，温度阈值显示为 38.0°C）。再次发热前须连续退热 72 小时。感染按共识标准分为微生物学确诊、临床定义或发热综合征。共 204 名成人接受 tisagenlecleucel（50%）或 axicabtagene（50%）治疗，中位年龄 64 岁（IQR：57–71），既往治疗中位数为 3 线（IQR：3–4）。131/204 人（64%）出现持续发热，共 161 次发热事件；其中 36 次（21%，涉及 28 人）为微生物学确诊感染，14 次（9%，14 人）为临床定义感染，110 次（69%，108 人）为不明原因发热。菌血症发生于 7/204 人（3.4%；共 9 次事件），其中 1 例为致死性多菌种菌血症。其他经微生物学确诊的感染包括艰难梭菌感染（36 例中的 7 例）、上呼吸道感染（13/36）和侵袭性真菌感染（5/36）。单因素分析中，早期微生物学确诊感染的风险因素包括使用 axicabtagene（风险比 HR=2.5，P=0.019）、3 级免疫效应细胞相关神经毒性（HR=3.4，P=0.012）以及中性粒细胞减少持续时间较长（原文绝对中性粒细胞计数阈值的指数和单位受损；HR=3.7，P=0.014）。未常规使用 FQ 预防时，早期菌血症发生率仍较低；初始持续发热多数并非感染所致。数据不支持在 CAR-T 治疗中普遍预防性使用 FQ。
Routine fluoroquinolone (FQ) prophylaxis may increase the risk of antimicrobial resistance, microbiome disruption, and Clostridioides difficile infection in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for hematological malignancy. In Australia, FQ prophylaxis is not routinely used. We evaluated the etiology of early fever following CAR-T to better understand the incidence of infections, particularly bloodstream infections, in a cohort not receiving FQ prophylaxis. This bicentric Australian retrospective study included adults receiving standard-of-care CD19 CAR-T therapy for DLBCL (2019 to 2023). The primary outcome was the cause of sustained fever ( 38.0 C on 1 days) from infusion to day 30. Recurrent fever required 72 h afebrile before a new fever. Infections were classified as microbiologically confirmed, clinically defined, or fever syndrome per consensus criteria. About 204 adults (median age 64 years, IQR: 57 to 71) received tisagenlecleucel (50%) and axicabtagene (50%), after a median of 3 prior therapies (interquartile range [IQR]: 3 to 4). Sustained fever occurred in 131/204 patients (64%), comprising 161 episodes. Of these, 36 (21%, 28pts) were microbiologically confirmed infections, 14 (9%, 14pts) were clinically defined infections, and 110 (69%, 108pts) were fevers of unknown origin. Bacteremia occurred in 7/204 patients (3.4%; 9 events), with one fatal polymicrobial bacteremia. Other microbiologically confirmed infections included C. difficile (7/36), URTI (13/36) and invasive fungal infection (5/36). Risk factors for early microbiologically confirmed infection in univariate analysis included axicabtagene product (hazard ratio [HR] = 2.5, P = .019), grade 3 immune-cell associated neurotoxicity (HR = 3.4, P = .012), and prolonged neutropenia (absolute neutrophil count .5 10 /L for 14 days; HR = 3.7, P = .014). Early bacteremia rates remain low without routine FQ prophylaxis. Initial sustained fevers are predominantly noninfectious. Our data do not support universal FQ prophylaxis in CAR-T therapy.
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