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一种新型细胞疗法治疗耐多药结核病的有效性

Effectiveness of a novel cellular therapy to treat multidrug-resistant tuberculosis.

作者信息

Skrahin Aliaksandr, Jenkins Helen E, Hurevich Henadz, Solodovnikova Varvara, Isaikina Yanina, Klimuk Dzmitri, Rohava Zoya, Skrahina Alena

机构信息

Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus; Belarus State Medical University, Minsk, Belarus.

Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

出版信息

Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S23. doi: 10.1016/j.ijmyco.2016.11.018. Epub 2016 Nov 29.

Abstract

BACKGROUND/OBJECTIVE: We urgently need novel treatments for multidrug-resistant tuberculosis (MDR-TB). Autologous mesenchymal stromal cell (MSC) infusion is one such possibility due to its potential to repair damaged lung tissue and boost immune responses. We aimed to assess the safety and effectiveness of MSC to improve treatment outcomes among MDR-TB patients.

METHODS

We analyzed treatment outcomes for 108 Belarusian MDR-TB patients receiving chemotherapy. Thirty-six patients (cases) also had MSCs collected, extracted, cultured, and reinfused (average time from chemotherapy start to infusion was 49days) in optimal dose; another 36 patients (without MSC treatment) were "study controls". We identified another control group: 36 patients from the Belarusian national surveillance database (surveillance controls) 1:1 matched to cases.

RESULTS

Successful outcomes were observed in 81% of cases, 42% of surveillance controls, and 39% of study controls. After adjusting for age, odds of a successful outcome were 6.5 (95% confidence interval, 1.2-36.2, p=0.032) times greater for cases than surveillance controls. Adjusting for other potential confounders increased the effect estimate while maintaining statistical significance. Cases were less likely (p=0.01) to be culture negative at 2months than surveillance controls, indicating a poorer initial prognosis in cases before (or shortly after) infusion. Radiological improvement was more likely in cases than in study controls.

CONCLUSION

MSC treatment could vastly improve treatment outcomes for MDR-TB patients. Our findings could revolutionize therapy options and have strong implications for future directions of MDR-TB therapy research.

摘要

背景/目的:我们迫切需要针对耐多药结核病(MDR-TB)的新型治疗方法。自体间充质基质细胞(MSC)输注是一种可能的方法,因为它有修复受损肺组织和增强免疫反应的潜力。我们旨在评估MSC改善MDR-TB患者治疗效果的安全性和有效性。

方法

我们分析了108例接受化疗的白俄罗斯MDR-TB患者的治疗结果。36例患者(病例组)还采集、提取、培养并以最佳剂量回输了间充质基质细胞(从开始化疗到输注的平均时间为49天);另外36例患者(未接受MSC治疗)为“研究对照组”。我们确定了另一个对照组:从白俄罗斯国家监测数据库中选取36例患者(监测对照组),与病例组1:1匹配。

结果

病例组81%、监测对照组42%和研究对照组39%观察到成功的治疗结果。在调整年龄后,病例组成功治疗结果的几率是监测对照组的6.5倍(95%置信区间,1.2 - 36.2,p = 0.032)。调整其他潜在混杂因素后,效应估计值增加且保持统计学显著性。病例组在2个月时培养转阴的可能性低于监测对照组(p = 0.01),表明在输注前(或输注后不久)病例组的初始预后较差。病例组的影像学改善比研究对照组更明显。

结论

MSC治疗可极大地改善MDR-TB患者的治疗效果。我们的研究结果可能会彻底改变治疗选择,并对MDR-TB治疗研究的未来方向产生重大影响。

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