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降钙素原水平阈值与嵌合抗原受体 T 细胞治疗患者的抗生素使用。

Procalcitonin level threshold and antibiotic use in patients receiving chimeric antigen receptor T-cell therapy.

机构信息

Intensive Care Unit, Westmead Hospital, Sydney, Australia.

Faculty of Medicine and Health, Sydney Medical School, University of Sydney, Sydney, Australia.

出版信息

Hematology. 2024 Dec;29(1):2381989. doi: 10.1080/16078454.2024.2381989. Epub 2024 Jul 31.

Abstract

BACKGROUND

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy are vulnerable to infection and sepsis. Treatment course is frequently complicated by cytokine release syndrome which is often clinically and biochemically indistinguishable from sepsis. Procalcitonin (PCT) levels have been examined as a promising biomarker for infection in this cohort of patients.

METHODS

In this study, we measured daily PCT levels for patients for fourteen days (or hospital discharge) after receiving CAR T-cells to determine threshold PCT values specific for infection compared to those without infection.

RESULTS

We present preliminary results of our enrolled cohort to date (sixteen patients). Infection was present in only 12.5% of patients. However, those diagnosed with sepsis had elevated PCT levels with a peak mean of 2.6 µg/L observed on the seventh day post-treatment compared to those without infection remaining below 0.5 µg/L. Furthermore, we observed a trend for early and liberal antibiotic administration within our cohort.

CONCLUSION

Our study highlights the challenges of antimicrobial stewardship in managing CAR T-cell therapy recipients. Our preliminary results underscore the utility of PCT in the risk-stratification and diagnosis of those patients at high risk for infectious complications after receiving CAR T-cell therapy and continue to advocate for a PCT threshold of 1.5 µg/L for diagnosing sepsis. Additionally, in the setting of CRS and lymphodepletion, where white cell count and CRP value are unreliable, a PCT value of < 0.5 µg/L may help exclude sepsis.

摘要

背景

接受嵌合抗原受体(CAR)T 细胞疗法的患者易感染和发生败血症。治疗过程中经常会出现细胞因子释放综合征,其在临床上和生化上与败血症难以区分。降钙素原(PCT)水平已被作为该患者群体感染的有前途的生物标志物进行了研究。

方法

在这项研究中,我们对接受 CAR T 细胞治疗后 14 天(或出院)的患者每天测量 PCT 水平,以确定与无感染患者相比,感染的特定 PCT 值阈值。

结果

我们目前报告了入组患者的初步结果(16 例)。感染仅见于 12.5%的患者。然而,那些被诊断为败血症的患者 PCT 水平升高,治疗后第 7 天的平均峰值为 2.6μg/L,而无感染的患者 PCT 水平仍低于 0.5μg/L。此外,我们观察到在我们的队列中早期和自由使用抗生素的趋势。

结论

我们的研究强调了在管理接受 CAR T 细胞疗法的患者时,对抗菌药物管理的挑战。我们的初步结果强调了 PCT 在风险分层和诊断接受 CAR T 细胞治疗后发生感染性并发症风险高的患者中的作用,并继续提倡使用 1.5μg/L 的 PCT 阈值来诊断败血症。此外,在 CRS 和淋巴细胞耗竭的情况下,白细胞计数和 CRP 值不可靠,PCT 值<0.5μg/L 可能有助于排除败血症。

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