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对于接受异基因干细胞移植的患者,采用肺量计进行筛查是预测其日后发生非感染性肺综合征的一项有用指标。

Screening with spirometry is a useful predictor of later development of noninfectious pulmonary syndromes in patients undergoing allogeneic stem cell transplantation.

作者信息

Thompson Philip A, Lim Andrew, Panek-Hudson Yvonne, Tacey Mark, Hijazi Ramzi, Ng Ashley P, Szer Jeff, Ritchie David, Bajel Ashish

机构信息

Department of Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Department of Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Biol Blood Marrow Transplant. 2014 Jun;20(6):781-6. doi: 10.1016/j.bbmt.2014.02.011. Epub 2014 Feb 16.

Abstract

Noninfectious pulmonary syndromes (NIPS) frequently complicate allogeneic stem cell transplantation (allo-SCT). The most common and serious is the bronchiolitis obliterans syndrome, characterized by irreversible fixed airflow obstruction, impaired quality of life, and a high mortality. Treatment for established symptomatic disease is relatively ineffective. We therefore sought to identify potential predictive factors for development of NIPS, which may identify patients at risk in whom earlier intervention may be of benefit. Spirometry and diffusing capacity for carbon monoxide were performed before allo-SCT, day 100, and 1 year after allo-SCT. We retrospectively analyzed spirometry in consecutive patients having allo-SCT from 2004 to 2010, along with computed tomography and bronchoalveolar lavage results to identify cases of NIPS. Cases of bronchiolitis obliterans syndrome were defined as per current National Institutes of Health consensus guidelines. Spirometry results and baseline variables were compared between patients with and without NIPS to identify early predictors and risk factors for NIPS. Of 235 assessable patients, 23 (9.8%) developed NIPS. Median time of onset was day 367 (interquartile range [IQR], 144 to 544 days). Changes in forced expiratory volume in 1 second (ΔFEV1.0) was the best predictor of later NIPS development. Median ΔFEV1.0 from pretransplant to day 100 in patients later developing NIPS was -12% (IQR, -25% to -1%) versus -1% (IQR, -7% to +6%) in unaffected patients, P = .002. From pretransplant to 1 year, ΔFEV1.0 was -19% (IQR, -37% to -6%) versus -3% (IQR, -10% to +4%) in patients later developing NIPS and unaffected patients, respectively, P < .001. Busulfan-based, but not total body irradiation-based, conditioning increased the risk of NIPS (hazard ratio, 9.4 [3.4 to 23.9], P < .001). No cases of NIPS were seen in the 53 patients who received in vivo T cell depletion with antithymocyte globulin (ATG, Genzyme Transplant, Cambridge, MA) (P < .0001). NIPS were associated with high transplant-related mortality relative to unaffected patients (hazard ratio, 6.6 [2.5 to 16.4], P < .001). Spirometry is a potentially useful screening test for identification of presymptomatic NIPS. We recommend 3-monthly spirometry surveillance for up to 2 years post-transplant. Our findings require prospective validation to identify patients in whom earlier intervention may potentially modify the natural history of this disease.

摘要

非感染性肺部综合征(NIPS)常使异基因干细胞移植(allo-SCT)变得复杂。最常见且严重的是闭塞性细支气管炎综合征,其特征为不可逆的固定气流阻塞、生活质量受损及高死亡率。针对已出现症状的疾病的治疗效果相对不佳。因此,我们试图确定NIPS发生的潜在预测因素,这可能有助于识别有风险的患者,对其进行早期干预或许有益。在allo-SCT前、第100天及allo-SCT后1年进行肺功能测定和一氧化碳弥散功能检测。我们回顾性分析了2004年至2010年连续接受allo-SCT患者的肺功能测定结果,以及计算机断层扫描和支气管肺泡灌洗结果以确定NIPS病例。闭塞性细支气管炎综合征病例根据当前美国国立卫生研究院的共识指南进行定义。比较有和没有NIPS患者的肺功能测定结果及基线变量,以确定NIPS的早期预测因素和风险因素。在235例可评估患者中,23例(9.8%)发生了NIPS。发病的中位时间为第367天(四分位间距[IQR],144至544天)。一秒用力呼气量的变化(ΔFEV1.0)是后期NIPS发生的最佳预测指标。后期发生NIPS的患者从移植前到第100天的中位ΔFEV1.0为-12%(IQR,-25%至-1%),而未受影响患者为-1%(IQR,-7%至+6%),P = 0.002。从移植前到1年,后期发生NIPS的患者和未受影响患者的ΔFEV1.0分别为-19%(IQR,-37%至-6%)和-3%(IQR,-10%至+4%),P < 0.001。基于白消安而非全身照射的预处理增加了NIPS的风险(风险比,9.4[3.4至23.9],P < 0.001)。在53例接受抗胸腺细胞球蛋白(ATG,Genzyme Transplant,马萨诸塞州剑桥)进行体内T细胞清除的患者中未观察到NIPS病例(P < 0.0001)。与未受影响的患者相比,NIPS与高移植相关死亡率相关(风险比,6.6[2.5至16.4],P < 0.001)。肺功能测定是识别无症状NIPS的潜在有用筛查试验。我们建议在移植后长达2年的时间里每3个月进行一次肺功能测定监测。我们的研究结果需要前瞻性验证,以确定哪些患者进行早期干预可能会改变这种疾病的自然病程。

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