Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.
Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.
复制标题
DOI：
10.1016/j.bbmt.2015.10.009
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Lee SJ
中科院分区：
文献类型：
--
作者：
Williams KM;Cheng GS;Pusic I;Jagasia M;Burns L;Ho VT;Pidala J;Palmer J;Johnston L;Mayer S;Chien JW;Jacobsohn DA;Pavletic SZ;Martin PJ;Storer BE;Inamoto Y;Chai X;Flowers MED;Lee SJ
异基因造血细胞移植（HCT）后闭塞性细支气管炎综合征（BOS）与高死亡率相关。目的：我们假设FAM（吸入氟替卡松，阿奇霉素和孟鲁司特）与短暂的类固醇脉冲可以避免新发BOS的进展。实验设计：我们在一项II期、单组、开放标签、多中心研究（NCT 01307462）中对此进行了测试。结果：36例患者在BOS诊断后6个月内入组。主要终点是治疗失败，定义为3个月时FEV1%下降10%或以上。在3个月时，6%（2/36，95% CI 1%-19%）的患者治疗失败（与历史对照组的40%相比，p<0.001）。FAM耐受性良好。48%的可评价患者（n=27）在3个月时类固醇剂量减少50%或更多。与入组相比，3个月时患者报告的SF-36社会功能评分和心理健康评分、FACT情感健康和肺部、皮肤、口腔的Lee症状评分以及总体总分在统计学上显著改善（n=24）。6个月时，36%的患者治疗失败（95% CI 21%-54%，n=13/36，6例记录失败，7例缺失肺功能检查）。6个月时的总生存率为97%（95% CI 84%-100%）。这些数据表明，FAM耐受性良好，FAM和类固醇脉冲治疗可阻止大多数患者新发BOS的肺功能下降，并允许减少全身类固醇暴露，这共同可改善生活质量。然而，尽管有FAM，进行性BOS仍需要额外的治疗。
Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. Purpose: We hypothesized that FAM (inhaled Fluticasone, Azithromycin, and Montelukast) with a brief steroid pulse could avert progression of new-onset BOS. Experimental design: We tested this in a phase II, single-arm, open label, multicenter study (NCT01307462). Results: Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater FEV1% decline at 3 months. At 3 months, 6% (2/36, 95% CI 1%–19%) had treatment failure (vs. 40% in historical controls, p<0.001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n=27). Patient-reported outcomes at 3 months were statistically significantly improved for SF-36 social functioning score and mental component score, FACT emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n=24). At 6 months, 36% had treatment failure (95% CI 21%–54%, n=13/36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% CI 84%–100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.